Autoimmune disorders

PRESENTER-Dr SHREYA
PRABHU
MODERATOR-Dr SHASHIKALA
K
1

 Immune reactions against self antigens—Autoimmunity
 Autoimmune disease is the faliure in recognizing its own
constituent parts which allows an immune response against
its own self and tissues.
 Any disease which results in such an aberrant immune
response is termed as autoimmune disease.
2

 The mere presence of autoantibodies does not indicate an
autoimmune disease
 Ideally, at least three requirements should be met before a
disorder is categorized as truely caused by autoimmunity:
1) The presence of an immune reaction specific for some self
antigen or self tissue
2) Evidence that such a reaction is not secondary to tissue
damage but is of primary pathogenic significance
3) The absence of another well-defined cause of the disease
3

IMMUNOLOGIC TOLERANCE
 Immunologic tolerance is the phenomenon of
unresponsiveness to an antigen induced by exposure of
lymphocytes to that antigen.
 Self-tolerance refers to lack of responsiveness to an
individual’s own antigens, and it underlies our ability to live in
harmony with our cells and tissues
4

MECHANISMS OF IMMUNLOGIC
TOLERANCE
 Central Tolerance:
 Negative selection or deletion
 Receptor editing
 Peripheral Tolerance:
 Anergy
 Suppression by regulatory T cells
 Deletion by apoptosis
5

9
SUPPRESSION BY REGULATORY T
CELLS
Cd4+ cells
that express
CD25, IL2
receptor
secretion of
immunosuppressive
cytokines such as IL-10 and
TGF-β
Express CTLA-4

MECHANISMS OF AUTOIMMUNITY
 Cause of autoimmune diseases is the failure of tolerance
 Autoimmunity arises from a combination of the inheritance of
susceptibility genes, which may contribute to the
breakdown of self-tolerance, and environmental triggers,
such as infections and tissue damage, which promote the
activation of self-reactive lymphocytes
11

 It is thought that susceptibility genes and environmental
triggers induce a number of changes that contribute to the
development of autoimmunity
 Defective tolerance or regulation
 Abnormal display of self antigens
 Inflammation or an initial innate immune response
13

Defective tolerance or regulation-
 Failure of the mechanisms that maintain self tolerance
Abnormal display of self antigens-
 Increased expression and persistence of self antigens that
are normally cleared
 Structural changes in these antigens resulting from
enzymatic modifications or from cellular stress or injury
14

Inflammation or an initial innate immune response-
 Microbes or cell injury may elicit local inflammatory reactions
resembling innate immune responses, and these may be
critical inducers of the autoimmune disease.
15

ROLE OF SUSCEPTIBILITY GENES
 Most autoimmune diseases are complex multigenic disorders
Association of HLA Alleles with Disease
 Among the genes known to be associated with autoimmunity, the
greatest contribution is that of HLA genes
Association of Non-MHC Genes with Autoimmune Diseases
 Polymorphisms in a gene called PTPN22
 Polymorphisms in the gene for NOD2
 Polymorphisms in the genes encoding the IL-2 receptor(CD25)
and IL-7 receptor α chains
17

ROLE OF INFECTIONS
 Autoimmune reactions may be triggered by infections
 Two mechanisms have been postulated
1. Induction of costimulators on APCs
2. Molecular mimicry
20

 Microbes may induce other abnormalities that promote
autoimmune reactions.
 Some viruses, such as Epstein-Barr virus (EBV) and HIV, cause
polyclonal B-cell activation, which may result in production of
autoantibodies
 Tissue injury that is common in infections may release self
antigens and structurally alter these antigens so that they are able
to activate T cells that would not be tolerant to these new, modified
antigens.
22

GENERAL FEATURES
 Autoimmune diseases tend to be chronic, sometimes with relapses
and remissions, and the damage is often progressive
 The clinical and pathologic manifestations of an autoimmune
disease are determined by the nature of the underlying immune
response
 The systemic diseases tend to involve blood vessels and
connective tissues, and therefore, they are often called collagen
vascular diseases or connective tissue diseases
24

SYSTEMIC LUPUS
ERYTHEMATOSUS
31

 Autoimmune disease involving multiple organs, characterized
by a vast array of autoantibodies, particularly antinuclear
antibodies (ANAs), in which injury is caused mainly by
deposition of immune complexes and binding of antibodies to
various cells and tissues
 Acute or insidious in its onset, and is typically a chronic, remitting
and relapsing, often febrile
32

 Disease is very heterogeneous- any patient may present with any
number of these clinical features
 1 in 2500
 Predominantly affects women,
 With a frequency of 1 in 700 among women of childbearing age
 Female-to-male ratio of 9 : 1 during the reproductive age group
33

34MALAR RASH
Fixed erythema,
flat or raised, over
the malar
eminences,
tending to spare
the nasolabial
folds

DISCOID RASH
Erythematous raised
patches with adherent
keratotic scaling and
follicular plugging
35

PHOTOSENSITIVIT
Y
Rash as a result of
unusual reaction to
sunlight
36

ORAL ULCERS
Oral or nasopharyngeal
ulceration, usually painless
37

ARTHRITIS
Nonerosive arthritis
involving two or more
peripheral joints,
characterized by
tenderness, swelling, or
effusion
38

SEROSITIS
>Pleuritis- history of
pleuritic pain or rub
heard by a physician
or evidence of
pleural effusion
>Pericarditis
39

Spectrum of Autoantibodies in SLE
 The hallmark of SLE is the production of autoantibodies
 Some antibodies recognize diverse nuclear and cytoplasmic
components of the cell
 Others are directed against cell surface antigens of blood cells
41

 Antinuclear antibodies (ANAs). These are directed against
nuclear antigens and can be grouped into four categories:
1. Antibodies to DNA,
2. Antibodies to histones,
3. Antibodies to nonhistone proteins bound to RNA, and
4. Antibodies to nucleolar antigens
42

 The most widely used method for detecting ANAs is Indirect
immunofluorescence
 The pattern of nuclear fluorescence suggests the type of
antibody present in the patient’s serum
43

HOMOGENOUS OR
DIFFUSE STAINING
OF NUCLEI
Usually reflects
antibodies to
chromatin, histones,
and, occasionally,
double-stranded DNA
Most common in SLE
44

SPECKLED
PATTERN
>most commonly observed
patterns of fluorescence and
therefore the least specific
>reflects the presence of
antibodies to non-DNA
nuclear constituents such as
Sm antigen,
ribonucleoprotein, and SS-A
and SS-B reactive antigens
45

CENTROMERIC
PATTERN
Pattern of staining of
anticentromeric
antibodies is seen in
some cases of
•Systemic sclerosis
•Sjogren’s syndrome
46

NUCLEOLAR
PATTERN
Refers to the presence of
few discrete spots of
fluorescence within the
nucleus and represents
antibodies to RNA
47

RIM OR
PERIPHERAL
STAINING
•Often indicates
antibodies to - ds DNA
•Sometimes to nuclear
envelope proteins
-
48

 These fluorescence pattern are not absolutely specific for the type of antibody
as many autoantibodies are present, combinations are frequent.
 Neverthless this staining pattern is considered of diagnostic value and the test
remains in use
 Antibodies to double-stranded DNA and the so-called Smith (Sm)
antigen are virtually diagnostic of SLE.
49

OTHER AUTOANTIBODIES-
 Host of other autoantibodies
 Some of which are directed against blood cells such as red cells,
platelets and lymphocytes.
 Others react with proteins in complex with phospholipids
50

ANTIPHOSPHOLIPID ANTIBODIES
 Present in 30-40%of lupus patients
 Directed against epitopes of plasma proteins that are in complex
with phospholipids
 Proteins are prothrombin, annexin V, β2-glycoprotein I, protein S,
and protein C
51

 Antibodies also bind to cardiolipin antigen, used in syphilis
serology and therefore lupus patients may have false positive test
for syphilis.
 Some of these antibodies interfere with in vitro clotting tests such
as PTT.
 Therefore these are sometimes referred to as LUPUS
ANTICOAGULANT
52

ETIOLOGY AND PATHOGENESIS
 Failure of the mechanism that maintain self tolerance -
fundamental defect in SLE
 Genetic and environmnental factors play an important role.
53

GENETIC FACTORS
SLE is a genetically complex disease with contribution from
MHC and multiple non MHC genes
 Family members of patients have an increased risk of
developing SLE
 Concordance : monozygotic twins(20%) > dizygotic twins
54

 Several genetic loci,HLA-DQ locus, have been identified that
may be associated with the disease
 These loci encode the proteins involved in lymphocyte
signalling and interferon response
 Both of this play a important role in lupus pathogenesis
55

Some patients have inherited deficiency of early complement
components such as C2, C4 or C1q
↓
Impaired removal of circulating immune complexes by the
mononuclear phagocyte system
↓
Tissue deposition
56

 Failure to clear immune complexes and loss of B cell self
tolerance.
 Deficiency of C1q defective phagocytic clearance of
apoptotic cells
 Many cells normally undergo apoptosis and if they are not
cleared their nuclear components may elicit immune
responses
57

IMMUNOLOGIC FACTORS
 FAILURE OF SELF TOLERANCE IN B CELLS
Results from
Defective elimination Defect in peripheral
of self reactive B cells tolerance mechanism
in bone marrow
58

CD 4+ HELPER T CELLS
-Specific for nucleosomal antigens
 Also escape tolerance and contribute to the production of high
affinity pathogenic auto antibodies
 These auto antibodies in SLE show characteristics of T cell
dependent auto antibodies produced in germinal centres
59

 TLR engagement-
 By nuclear DNA and RNA contained in immune complexes may
activate B lymphocytes.
 These TLRs function normally to sense microbial products
 Thus, B cells specific for nuclear antigens may get second signals
from TLRs and may be activated, resulting in increased production
of antinuclear autoantibodies
60

 TYPE I INTERFERONS
 Play a role in lymphocyte activation
 Type I interferons are antiviral cytokines
 Self nucleic acids mimic their microbial counterparts
 OTHER CYTOKINES
 TNF family member BAFF- promotes survival of B cells
61

ENVIRONMENTAL FACTORS
 EXPOSURE TO UV LIGHT
 Exacerbates the disease in many individuals
 Induces apoptosis in cells and may alter the DNA in such a way
that it becomes immunogenic
 In addition UV light may modulate the immune response
62

 GENDER BIAS:
 Partly attributable to actions of sex hormones
 Partly related to genes on the X chromosome, independent of
hormone effects
 DRUGS
 Hydralazine, procainamide, and Dpenicillamine can induce an SLE
like response in humans
63

MECHANISM OF TISSUE INJURY
 Most of the systemic lesions are caused by immune
complexes (Type III hypersensitivity)
 DNA and anti DNA complexes  detected in glomeruli and small
blood vessels
 Serum complement is decreased and granular deposits of
complement and immunoglobulins in glomeruli  support immune
complex nature of the disease.
 T cell infiltrates are also frequently seen in kidneys
65

 Autoantibodies specific for blood cells opsonize these cells and
promote their phagocytosis and lysis
 ANAs which are involved in immune complex formation cannot
penetrate the intact cells
-If nuclei of the cells are exposed, ANAs can bind to them
-In tissues nuclei of damaged cells react with ANAs and loose
their chromatin pattern and become homogenous
66

- To produce so called HEMATOXYLIN OR LE BODIES
 Related to this phenomenon is the LE cell which is readily
seen when the blood is agitated invitro.
 LE CELL:
Any phagocytic leucocyte that has engulfed the denatured
nucleus of an injured cell.
67

ANTIPHOSPHOLIPID ANTIBODY SYNDROME
 Venous and arterial thromboses which may be associated with
miscarriages and focal cerebral or ocular ischaemia.
 This constellation of clinical features in association with lupus
is referred to as the secondary antiphospholipid antibody
syndrome.
 Some patients develop these antibodies without associated
with SLE. They are said to have the primary antiphospholipid
antibody syndrome
68

 The neuropsychiatric manifestations of SLE have
been attributed to antibodies that react with neurons or
receptors for various neurotransmitters and cross the
BBB.
69

MORPHOLOGY
 The most characteristic lesions result from immune
complex deposition in blood vessels, kidneys connective
tissue and skin.
70

BLOOD VESSELS
 An acute necrotising vasculitis involving capillaries, small
arteries and arterioles
 The arteritis is characterised by fibrinoid deposits in blood
vessel walls.
 In chronic stages, vessels undergo fibrous thickening with
luminal narrowing.
72

KIDNEY
 Clinical evidence of renal involvement as determined by urine
analysis or impaired renal function is seen in approximately 40-
50% of patients with SLE.
 The clinical spectrum of lupus nephritis is wide, encompassing
-Acute nephritic syndrome,
-Nephrotic syndrome,
-Acute and chronic renal failure and
-Isolated abnormalities in the urinary sediment
73

 Result of deposition of immune complexes that are regularly
present in the mesangium or along the entire basement membrane
and sometimes throughout the glomerulus
 Both in situ formation and deposition of preformed circulating
immune complexes may contribute to the injury
 Six patterns of glomerular disease are seen
 Class I is the least common and class IV is the most common
pattern
74

 The pathologic findings of lupus nephritis are extremely
diverse and may occur in all four renal compartments -
Glomeruli - tubules -interstitium - blood vessels
 The diversity may be the result of differences in the immune
response in different patients or in the same individual over a
period of time
75

CLASS I (MINIMAL MESANGIAL LUPUS
NEPHRITIS)
 Glomeruli appear normal by light microscopy
 On immunofloresence/electron microscopy show immune
complex deposits in mesangium
 Patients manifest with
- Mild microscopic hematuria
- Mild proteinuria
- Renal function - normal
77

CLASS II (MESANGIAL PROLIFERATIVE LUPUS
NEPHRITIS)
 Defined by
 Any degree of mesangial hypercellularity and/or mesangial
matrix expansion as seen by light microscopy
 Demonstration of immune deposits by immunoflorescence and
electron microscopy
78

CLASS III (FOCAL LUPUS NEPHRITIS)
 Defined by involvement of fewer than 50% of all glomeruli
 Lesions may be segmental or global
 Affected glomeruli exhibit swelling and proliferation of endothelial
and mesangial cells associated with leukocyte accumulation,
capillary necrosis, and hyaline thrombi
 Often extracapillary proliferation associated with focal necrosis and
crescent formation
79

 .
Focal proliferative
glomerulonephritis, with
two focal necrotizing
lesions at the 11 o’clock
and 2 o’clock positions
(H&E stain).
Extracapillary
proliferation is not
prominent in this case
80

 The clinical presentation ranges from mild hematuria and
proteinuria to acute renal insufficiency.
 Red cell casts in the urine are common when the
disease is active.
 Some patients progress to diffuse glomerulonephritis
81

CLASS IV (DIFFUSE LUPUS NEPHRITIS)
 Defined as segmental and /or global endocapillary
glomerulonephritis affecting 50% or more of the glomeruli
included in the biopsy
 Lesions are similar to class III but tend to be more diffuse
and global and immune complexes are more abundant
 It is the pathologic continum of class III since the
difference between the classes is quantitative rather than
qualitative.
82

 Lesions may be segmental or global
 Subclassified as class iv segmental ( iv-s) or class iv global (iv-g)
 Involved glomeruli show proliferation of endothelial, mesangial and
epithelial cells
 Subendothelial immune complex deposits may create a
circumferential thickening of the capillary wall, forming “wire loop”
structures on light microscopy
 Lesions may progress to scarring of glomeruli
89

The immune deposits
in subendothelial
areas may produce
marked thickening of
the capillary walls to
form the characteristic
“WIRE LOOP
LESIONS”.
90

On occasion capillary
lumina can be occluded by
massive deposition of
immune complexes-
“HYALINE THROMBI”.
91

 IMMUNOFLORESCENCE
 Reveal > one class of Ig in a coarse granular pattern in the
mesangium and peripheral capillary walls in all glomeruli
 IgG-almost invariably present
IgM and IgA-also frequently found
when all three are found this pattern is often referred to as “FULL
HOUSE”, an immunoflorescent profile which is considered
characteristic of lupus nephritis.
92

CLINICAL PICTURE
 Severe
 Hematuria as well as proteinuria.
 Hypertension
 Mild to severe renal insufficiency
97

Electron micrograph of a
renal glomerular capillary
loop from a patient with
SLE nephritis.
Subendothelial dense
deposits (arrowheads)
correspond to “wire
loops” seen by light
microscopy
98

Deposition of IgG
antibody in a granular
pattern, detected by
immunofluorescence.
99

CLASS V (MEMBRANOUS LUPUS
NEPHRITIS)
 Continous sub epithelial immune complex deposits-
diffuse thickening of the capillary walls or their
morphologic sequale by light microscopy
 Membranous changes may occur alone or with a
background of mesangial hypercellularity and mesangial
immune complex deposits
100

Under light microscope,
the peripheral glomerular
capillary walls often
appear diffusely
thickened and the so
called “SPIKE AND
DOME” pattern may be
demonstrated
101

 The immune complexes are usually accompanied by increased
production of basement membrane-like material
 By electron microscopy GBM shows same ultrastructural changes
seen in idiopathic membranous glomerulonephritis
 All patients will have proteinuria at presentation and
60-70%have the nephrotic syndrome.
 About 50% of the patients have hematuria.
102

CLASS VI (ADVANCED SCLEROSING LUPUS
NEPHRITIS)
 Global glomerulosclerosis affecting over 90% of the
glomeruli without residual activity
 Represents end-stage renal disease
103

 Changes in the interstitium and tubules are frequently
present
 Tubulointerstitial lesions may be the dominant abnormality
104

SKIN
 Characteristic erythema affects the face along the bridge of the
nose and cheeks (the “butterfly” rash) in approximately 50% of
patients
 Urticaria, bullae, maculopapular lesions, and ulcerations also
occur.
 Exposure to sunlight incites or accentuates the erythema.
105

SKIN
1. Vacuolar degeneration of
the basal layer of the
epidermis
2. In the dermis, there is
variable edema and
perivascular inflammation
3. Vasculitis with fibrinoid
necrosis
106

In about 90% of the
clinically involved skin on
direct immunoflorescence
shows the immune
complex deposition along
the dermoepidermal
junction resulting in
formation of an irregular
band
107

JOINTS
 Non erosive synovitis with little deformity
108

CENTRAL NERVOUS SYSTEM
 Neuropsychiatric symptoms- due to acute vasculitis
 Non inflammatory occlusion of small vessels by intimal
proliferation is noted
 May be due to endothelial damage by autoantibodies or
immune complexes
109

PERICARDITIS AND OTHER SEROSAL CAVITY INVOLVEMEMT
 Inflammation of serosal lining membranes-acute, subacute or
chronic
 Acute phase – mesothelial surface are covered with fibrous
exudate
 Later they become thickened opaque and coated with shaggy
fibrous tissue leading to partial/total obliteration of the serosal
cavity.
110

CARDIOVASCULAR SYSTEM
 Manifest as damage to any layer of the heart
 Symptomatic or asymptomatic
 Pericardial involvement- 50% of the patients
 Valvular abnormalities, mitral or aortic – diffuse leaflet thickening
associated with dysfunction
 Myocarditis /mononuclear cell infiltratation - less common
111

 Valvular endocarditis (Libman sacks)- common
 Increasing number of patients have evidence of coronary artery disease
owing to atherosclerosis.
 Risk factors for atherosclrosis –hypertension, obesity and hyperlipidemia
are commonly seen in SLE patients
 In addition to immune complexes and antiphospholipid antibodies 
endothelial damage atherosclerosis
112

1. Libman-Sacks endocarditis
of the mitral valve in lupus
erythematosus
2. The vegetations attached to
the margin of the thickened
valve leaflet
113

SPLEEN
 Splenomegaly ,capsular thickening and follicular hyperplasia
– more common features
 Arteries may show concentric intimal and smooth muscle
hyperplasia producing onion skin lesions.
114

 LUNGS : In addition to pleuritis and pleural effusion which are
present in almost 50% of the patients in some cases there is
chronic interstial fibrosis and secondary pulmonary
hypertension – but not specific to SLE.
 OTHER ORGANS AND TISSUES : LE or hematoxylin bodies
in the bone marrow or other organs - strongly indicative of
SLE. Lymph nodes may be enlarged with hyperplastic follicles
or even demostrate necrotising lymphadenitis.
115

CHRONIC DISCOID LUPUS
ERYTHEMATOSUS
 Skin manifestations may mimic SLE, but systemic manifestations
are rare
 Disease is usually confined to the skin- skin plaques and atrophy
 35% of patients show a positive test for ANAs but antibodies to
double-stranded DNA are rarely present
 Immunofluorescence studies of skin biopsy specimens show
deposition of immunoglobulin and C3 at the dermoepidermal
junction
116

SUBACUTE CUTANEOUS LUPUS
ERYTHEMATOSUS
 Also presents with predominant skin involvement
 Skin rash in this disease tends to be widespread, superficial, and
nonscarring
 Strong association with antibodies to the SS-A antigen and with
the HLA-DR3 genotype
 Thus seems to define a group intermediate between SLE and
lupus erythematosus localized only to skin
117

DRUG-INDUCED LUPUS
ERYTHEMATOSUS
 Develop in patients receiving a variety of drugs
 Drugs are associated with the development of ANAs
 Multiple organs are affected, renal and central nervous system
involvement is distinctly uncommon
 Antibodies specific for double-stranded DNA are rare, but there is
an extremely high frequency of antibodies specific for histones
118

 Chronic disease characterized by dry eyes
(keratoconjunctivitis sicca) and dry mouth (xerostomia)
resulting from immunologically mediated destruction of the
lacrimal and salivary glands
 It occurs as
 Primary form -an isolated disorder, known as the sicca syndrome or
 Secondary form-in association with another autoimmune disease
120

ETIOLOGY
 Lymphocytic infiltration and fibrosis of the lacrimal and salivary glands(The infiltrate
contains predominantly activated CD4+ helper T cells and some B cells, including plasma
cells)
 75% of patients have rheumatoid factor
 ANAs are detected in 50% to 80% of patients
 A host of other organ-specific and non–organ-specific antibodies have also been
identified
121

 Antibodies directed against two ribonucleoprotein antigens, SS-A (ro) and SS-
B (la)- detected in as many as 90% of patients- serological markers
 Shows some association with certain HLA alleles
 Linkage of the primary form with HLA-B8, HLA-DR3, and DRW52,HLA-DQA1
and HLA-DQB1 loci
 In patients with anti-ss-a or anti-ss-b antibodies, specific alleles of HLA-DQA1
and HLA-DQB1 are frequent
122

PATHOGENESIS
 Aberrant T-cell and B-cell activation are both implicated.
 The initiating trigger may be a viral infection of the salivary glands,
which causes local cell death and release of tissue self antigens.
 In genetically susceptible individuals, CD4+ T cells and B cells specific
for these self antigens may have escaped tolerance and are able to
react.
 The result is inflammation, tissue damage, and, eventually, fibrosis.
123

MORPHOLOGY
 Lacrimal and salivary glands are the major targets of the disease.
 The earliest histologic finding in both the major and the minor salivary
glands is periductal and perivascular lymphocytic infiltration.
 The lymphocytic infiltrate becomes extensive, in the larger salivary
glands lymphoid follicles with germinal centers may be seen.
124

 The ductal lining epithelial cells may show hyperplasia, thus
obstructing the ducts.
 Later there is atrophy of the acini, fibrosis, and hyalinization
 Still later in the course atrophy and replacement of parenchyma
with fat are seen.
 Intense lymphoid infiltrate - appearance of a lymphoma.
125

SJOGREN
SYNDROME
Enlargement of the
salivary gland
126

SJOGREN
SYNDROME
Intense lymphocytic and
plasma cell infiltration
with ductal epithelial
hyperplasia in a salivary
gland
127

CLINICAL FEATURES
 The lack of tears leads to drying of the corneal epithelium, which
becomes inflamed, eroded, and ulcerated;
 The oral mucosa may atrophy, with inflammatory fissuring and
ulceration
 Dryness and crusting of the nose may lead to ulcerations and even
perforation of the nasal septum
128

 Occurs most commonly in women between the ages of 50 and 60.
 The keratoconjunctivitis produces blurring of vision, burning, and
itching, and thick secretions accumulate in the conjunctival sac.
 The xerostomia results in difficulty in swallowing solid foods, a
decrease in the ability to taste, cracks and fissures in the mouth,
and dryness of the buccal mucosa
129

 Parotid gland enlargement is present in half the patients;
 Dryness of the nasal mucosa, epistaxis, recurrent bronchitis, and
pneumonitis
 Extraglandular manifestations include synovitis, diffuse pulmonary
fibrosis, and peripheral neuropathy.
 Glomerular lesions are extremely rare in sjögren syndrome but
defects of tubular function are often seen
130

 The combination of lacrimal and salivary gland inflammatory
involvement is called Mikulicz syndrome, from any cause,
including sarcoidosis, lymphoma, and other tumors.
 Biopsy of the lip is essential for the diagnosis of Sjögren
syndrome.
131

 The lymph nodes of patients with Sjögren syndrome are often
hyperplastic,
 The most intense lymphocytic response is seen in lacrimal and
salivary glands
 In early stages of the disease, this immune infiltrate consists of a
mixture of polyclonal T and B cells.
 About 5% of Sjögren patients develop lymphoma, an incidence that is
40-fold greater than normal
132

SYSTEMIC
SCLEROSIS
(SCLERODERMA)
133

Systemic sclerosis is characterized by:
1. Chronic inflammation thought to be the result of autoimmunity,
2. Widespread damage to small blood vessels, and
3. Progressive interstitial and perivascular fibrosis in the skin and multiple
organs
134

 The skin is most commonly affected
 But the gastrointestinal tract, kidneys, heart, muscles, and lungs
also are frequently involved
 Diffuse scleroderma-
 widespread skin involvement at onset, with rapid progression and
early visceral involvement
 Limited scleroderma-
 skin involvement is often confined to fingers, forearms, and face
135

 Some patients develop CREST SYNDROME
 Combination of
 Calcinosis
 Raynaud phenomenon
 Esophageal dysmotility
 Sclerodactyly
 Telangiectasia
136

ETIOLOGY AND PATHOGENESIS
Autoimmunity-
 CD4+ T cell responding to an unidentified antigen accumulate in the skin
release cytokines that activate inflammatory cells and fibroblasts.
 Cytokines produced- TGF-β and IL-13, stimulate transcription of genes that
encode collagen and other extracellular matrix proteins (e.G., Fibronectin)
in fibroblasts.
 Other cytokines recruit leukocytes and propagate the chronic inflammation
137

Vascular damage-
 Microvascular disease is consistently present early in the course,may be the
initial lesion.
 Intimal proliferation is evident in the digital arteries.
 Capillary dilation with leaking, as well as destruction
 Nailfold capillary loops are distorted
138

Fibrosis-
 Characteristic of the disease
 Culmination of multiple abnormalities including
 The accumulation of alternatively activated macrophages,
 Actions of fibrogenic cytokines produced by infiltrating leukocytes,
 Hyperresponsiveness of fibroblasts to these cytokines, and
 Scarring following upon ischemic damage caused by the vascular
lesions
139

MORPHOLOGY
Skin-
 Diffuse, sclerotic atrophy of the skin
 Begins in the fingers and distal regions of the upper extremities and extends
proximally to involve the upper arms, shoulders, neck, and face
 Histologically, there are edema and perivascular infiltrates containing CD4+ T
cells, together with swelling and degeneration of collagen fibers
 Capillaries and small arteries (150 to 500 μm in diameter)show thickening of the
basal lamina, endothelial cell damage, and partial occlusion
140

 Progression of the disease, there is increasing fibrosis of the
dermis, which becomes tightly bound to the subcutaneous
structures
 There is marked increase of compact collagen in the dermis,
usually with thinning of the epidermis, loss of rete pegs, atrophy of
the dermal appendages, and hyaline thickening of the walls of
dermal arterioles and capillaries
 Focal and sometimes diffuse subcutaneous calcifications may
develop, especially in patients with the CREST syndrome
141

 Advanced stages the fingers take on a tapered, clawlike
appearance with limitation of motion in the joints, and the face
becomes a drawn mask
 Loss of blood supply may lead to cutaneous ulcerations and to
atrophic changes in the terminal phalanges- autoamputation
142

Systemic
sclerosis
The extensive
subcutaneous fibrosis
has virtually immobilized
the fingers, creating a
clawlike flexion deformity.
Loss of blood supply has
led to cutaneous
ulcerations
143

144
A, Normal skin. B, Skin biopsy from a patient with systemic sclerosis. Note the extensive
deposition of dense collagen in the dermis with virtual absence of appendages and foci of
inflammation

Alimentary tract-
 Affected in approximately 90% of patients
 Progressive atrophy and collagenous fibrous replacement of the
muscularis develop at any level of gut- severe in esophagus
 The lower two thirds of the esophagus often develops a rubber-
hose–like inflexibility
145

 The mucosa is thinned and may be ulcerated
 There is excessive collagenization of the lamina propria and
submucosa.
 Loss of villi and microvilli in the small bowel is the basis for the
malabsorption syndrome
146

Musculoskeletal System-
 Inflammation of the synovium, associated with hypertrophy and
hyperplasia of the synovial soft tissues, later fibrosis
Kidneys-
 In 2/3rd of patients
 Most prominent are the vascular lesions
 Interlobular arteries show intimal thickening as a result of
deposition of mucinous or finely collagenous material
147

Lungs-
 In more than 50% of individuals
 Manifest as pulmonary hypertension and interstitial fibrosis
Heart-
 Pericarditis with effusion, myocardial fibrosis, and thickening of
intramyocardial arterioles occur in one third of the patients.
148

 Chronic inflammatory disorder of autoimmune origin that may
affect many tissues and organs but principally attacks the joints,
producing a nonsuppurative proliferative and inflammatory
synovitis
 Progresses to destruction of the articular cartilage and ankylosis of the
joints
 Extraarticular lesions may involve skin, heart, blood vessels and lungs
 The disease peaks in the second to fourth decades and is three times
more common in women than men.
150

Pathogenesis
 Genetic predisposition and environmental factors
 The pathologic changes are mediated by antibodies against
self-antigens and cytokine-mediated inflammation
 CD4+ T helper (TH) cells may initiate the autoimmune
response in RA by reacting with an arthritogenic agent
151

Cytokines involved
 IFN-γ from TH1 cells
 activates macrophages and resident synovial cells
 IL-17 from TH17 cells
 recruits neutrophils and monocytes
 TNF and IL-1 from macrophages
 stimulates resident synovial cells to secrete proteases that destroy
hyaline cartilage
 RANKL expressed on activated T cells
 stimulates bone resorption
152

 Antibodies produced in lymphoid organs and in the synovium are
specific for citrullinated peptides (CCPs)
 Antigen-antibody complexes containing citrullinated fibrinogen, type
II collagen, α-enolase and vimentin deposit in the joints
 80% of patients have serum IgM or IgA autoantibodies that bind to
the Fc portions of their own IgG.
 These autoantibodies are called rheumatoid factor
 Deposit in joints as immune complexes
153

ARTHRITOGEN
 Specific HLA-DRB1 alleles are linked to rheumatoid arthritis,
 And these alleles share a common sequence of amino acids
in a polymorphic region of the β chain, which is designated
the shared epitope
 The environmental arthritogen- uncertain.
 CCPs are produced during inflammation (so insults such as
infection and smoking may promote citrullination of self-proteins,creating
new epitopes that trigger autoimmune reactions)
154

MORPHOLOGY
Joints-
 Symmetric arthritis, affecting the small joints of the hand and feet
 The synovium becomes grossly edematous, thickened, and
hyperplastic, transforming its smooth contour to one covered by
delicate and bulbous villi
156

The characteristic histologic features:
 Synovial cell hyperplasia and proliferation
 Dense inflammatory infiltrates (frequently forming lymphoid follicles) of
CD4+ helper T cells, B cells, plasma cells, dendritic cells, and
macrophages increased vascularity due to angiogenesis
 Fibrinopurulent exudate on the synovial and joint surfaces
 Osteoclastic activity in underlying bone, allowing the synovium to
penetrate into the bone and cause periarticular erosions and
subchondral cysts
157

 Together, the above changes produce a pannus: a mass of
edematous synovium, inflammatory cells, granulation tissue,
and fibroblasts that grows over the articular cartilage and
causes its erosion
 In time, after the cartilage has been destroyed, the pannus
bridges the apposing bones to form a fibrous ankylosis,
which eventually ossifies and results in fusion of the bones,
called bony ankylosis
158

Rheumatoid
arthritis
Schematic view of the joint
lesion
159

160
B, Low magnification reveals marked synovial hypertrophy with formation of
villi.
C, At higher magnification, subsynovial tissue containing a dense lymphoid
aggregate

Skin-
 Rheumatoid subcutaneous nodules- Most common lesions
 occur in approximately 25% of affected individuals, usually
those with severe disease
 arise in regions of the skin that are subjected to pressure
161

 Rheumatoid nodules are firm, nontender, and round to oval,
and in the skin arise in the subcutaneous tissue.
 Microscopically they resemble necrotizing granulomas with a
central zone of fibrinoid necrosis surrounded by a prominent
rim activated macrophages and numerous lymphocytes and
plasma cells
162

Rheumatoid nodule
composed of central
necrosis rimmed by
palisaded histiocytes.
163

Blood vessels-
 Acute necrotizing vasculitis involves small and large arteries
 Segments of small arteries such as vasa nervorum and the digital
arteries are obstructed by an obliterating endarteritis resulting in
peripheral neuropathy, ulcers, and gangrene
 Leukocytoclastic vasculitis produces purpura, cutaneous ulcers,
and nail bed infarction
164

Clinical Course
 Begin as slowly and insidiously with malaise, fatigue, and
generalized musculoskeletal pain
 After several weeks to months the joints become involved
 Generally symmetrical and the small joints are affected before the
larger ones
 Involved joints are swollen, warm, painful, and particularly stiff
when rising in the morning or following inactivity
165

 The typical patient has progressive joint enlargement, decreased
range of motion evolving to complete ankylosis, with the greatest
damage occurring in the first 4 or 5 years
 Produces the characteristic radial deviation of the wrist, ulnar
deviation of the fingers and flexion-hyperextension of the fingers
(swan-neck deformity, boutonnière deformity).
 Radiographic hallmarks are joint effusions and juxta-articular
osteopenia with erosions and narrowing of the joint space and loss of
articular cartilage
166

 The diagnosis of RA is supported by
1. Characteristic radiographic findings
2. Sterile, turbid synovial fluid with decreased viscosity, poor
mucin clot formation, and inclusion-bearing neutrophils,
3. The combination of rheumatoid factor and anti-ccp antibody
(80% of patients)
168

Therapies include
 Corticosteroids
 Synthetic and biologic disease-modifying drugs such as
methotrexate, and, most notably, antagonists of TNF
169

 uncommon, heterogeneous group of disorders characterized
by injury and inflammation of mainly the skeletal muscles.
 Three distinct disorders- dermatomyositis, polymyositis, and
inclusion-body myositis-considered the three main primary
inflammatory myopathies
171

DERMATOMYOSITIS
 systemic autoimmune disease that typically presents with proximal muscle
weakness and skin changes
 Pathogenesis-
 damage to small blood vessels contributes to muscle injury
 vasculopathic changes- telangiectasias (dilated capillary loops) in the nail folds,
eyelids, and gums
 Biopsies of muscle and skin may show deposition of the complement membrane
attack complex (C5b-9) within capillary beds in both tissues
172

certain autoantibodies tend to be associated-
 Anti-Mi2 antibodies (directed against a helicase) show a strong
association with prominent Gottron papules and heliotrope rash
 Anti-Jo1 antibodies (directed against the enzyme histidyl t-RNA
synthetase) are associated with interstitial lung disease, nonerosive
arthritis, and a skin rash described as “mechanic’s hands.”
 Anti-P155/P140 antibodies (directed against several transcriptional
regulators) are associated with paraneoplastic and juvenile cases of
dermatomyositis
173

 Muscle biopsies of affected patients show infiltrates of mononuclear inflammatory
cells that tend to be most pronounced in the perimysial connective tissue and
around blood vessels.
 Sometimes there is a distinctive pattern in which myofiber atrophy is accentuated
at the edges of the fascicles— perifascicular atrophy
174

Clinical Features
 Muscle weakness, symmetric, proximal muscles
 Various rashes, the most characteristic ones are
 A lilac colored discoloration of the upper eyelids associated with
periorbital edema (heliotrope rash)
 A scaling erythematous eruption or dusky red patches over the
knuckles,elbows, and knees (gottron papules)
176

 Dysphagia
 Interstitial lung disease
 Cardiac involvement
 Juvenile and adult forms are recognized
 Dermatomyositis is the most common inflammatory
myopathy in children
177

POLYMYOSITIS
 Adult-onset inflammatory myopathy that shares myalgia and
weakness with dermatomyositis but lacks its distinctive
cutaneous features
 Typically develop symmetric proximal muscle involvement
Pathogenesis-
 Uncertain, believed to have an immunologic basis
 CD8-positive cytotoxic T cells are a prominent part of the
inflammatory infiltrate in affected muscle
178

Morphology-
 Mononuclear inflammatory cell infiltrates are present- usually
endomysial in location
 Myofibers with otherwise normal morphology appear to be invaded
by mononuclear inflammatory cells
 Degenerating necrotic, regenerating, and atrophic myofibers are
typically found in a random or patchy distribution
179

INCLUSION BODY MYOSITIS
 Disease of late adulthood, the most common
inflammatory myopathy in patients >65 years
 Slowly progressive muscle weakness, severe in the
quadriceps and the distal upper extremity muscles
 Most myositis-associated autoantibodies are absent,
although an antibody to cn1a has recently been described
180

Morphology
Number of features that are similar to those found in
polymyositis:
 Patchy often endomysial mononuclear inflammatory cell infiltrates
rich in CD8+ T-cells
 Increased sarcolemmal expression of MHC class I antigens
 Focal invasion of normal appearing myofibers by inflammatory
cells
 Admixed degenerating and regenerating myofibers
181

Features more typical or even specific for inclusion body myositis,
as follows:
 Abnormal cytoplasmic inclusions described as “rimmed vacuoles”
 Tubolofilamentous inclusions in myofibers, seen by electron microscopy
 Cytoplasmic inclusions containing proteins typically associated with
neurodegenerative diseases, like beta-amyloid, TDP-43, and ubiquitin
 Endomysial fibrosis and fatty replacement, reflective of a chronic
disease course
182

Inclusion body
myositis
Showing myofibers
containing rimmed
vacuoles—inclusions
with reddish granular
rimming
183

Treatment-
 Corticosteroids
 Immunosuppressive drugs are used in steroid-resistant
disease
 Intravenous immunoglobulin(IVIG), cyclophosphamide,
cyclosporine, and rituximab
184

MIXED CONNECTIVE TISSUE DISEASE
185

 Used to describe a disease with clinical features that are a mixture of
the features of SLE, systemic sclerosis, and polymyositis.
 Characterized serologically by high titers of antibodies to
ribonucleoprotein particle-containing u1 ribonucleoprotein
 Typically, presents with synovitis of the fingers, raynaud phenomenon
and mild myositis, but renal involvement is modest.
186

 Good response to corticosteroids
 Not a distinct entity but that different patients represent
subsets of sle, systemic sclerosis, and polymyositis
 Over time, evolve into classic sle or systemic sclerosis
 Serious complications include
 Pulmonary hypertension
 Interstitial lung disease
 Renal disease
187

 Newly recognized constellation of disorders characterized by
 Tissue infiltrates dominated by igg4 antibody-producing plasma cells and
lymphocytes,
 Storiform fibrosis,
 Obliterative phlebitis,
 Usually increased serum IgG4
189

 Described in virtually every organ system:
 The biliary tree, salivary glands, periorbital tissues, kidneys, lungs,
lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium,
and skin
 Mikulicz syndrome , riedel thyroiditis, idiopathic retroperitoneal
fibrosis, autoimmune pancreatitis and inflammatory pseudotumors
of the orbit, lungs,and kidneys- part of igg4-rd spectrum
190

 The pathogenesis of this condition is not understood
 IgG4 production in lesions is a hallmark of the disease
191

 Systemic vasculitis of small- or medium-sized muscular
arteries
 30% of patients with PAN have chronic hepatitis B and
deposits containing hbsag-hbsab complexes in affected
vessels
 The inflammatory process weakens the arterial wall and can
lead to aneurysms or even rupture
193

 Characterized by segmental transmural necrotizing
inflammation of small- to medium sized arteries
 Acute phase- there is transmural inflammation of the arterial
wall with a mixed infiltrate of neutrophils, eosinophils, and
mononuclear cells, frequently accompanied by fibrinoid
necrosis
 Chronic phase-acute inflammatory infiltrate is replaced by
fibrous thickening of the vessel wall
195

 Impaired perfusion with ulcerations, infarcts, ischemic atrophy, or
hemorrhages may be the first sign of disease
 Clinical manifestations result from ischemia and infarction of
affected tissues and organs
 A “classic” presentation-rapidly accelerating hypertension
 Abdominal pain and bloody stools
 Diffuse myalgias;
 Peripheral neuritis
196

 Graves disease is an autoimmune disease where the thyroid
is overactive, producing an excessive amount of thyroid
hormones
 This is caused by thyroid autoantibodies that activate the
TSH-receptor, thereby stimulating thyroid hormone synthesis
and secretion, and thyroid growth (causing a diffusely
enlarged goiter)
199

Graves disease
There is diffuse
symmetric enlargement
of the gland and a beefy
deep red parenchyma
203

Graves disease
The follicles are lined by
tall, columnar epithelium.
The crowded,enlarged
epithelial cells project into
the lumens of the follicles.
These cells actively resorb
the colloid in the centers of
the follicles, resulting in the
scallopedappearance of the
edges of the colloid.
204

 Autoimmune disease that results in destruction of the
thyroid gland and gradual and progressive thyroid failure
 Is characterized by the destruction of thyroid cells by various
cell- and antibody-mediated immune process.
 Caused by auto Ab of IgG & IgM type against the
constituents of thyroid gland Hashimoto’s thyroiditis
206

207Abs are specifically formed for thyroid perioxidase
&thyroglobulin
Abs interact with the enzyme
Development of inflammation in the thyroid gland
Thyroid gland is destroyed
Patient ultimately rendered hypothyroid

 Uncommon disorder resulting from progressive destruction of the adrenal cortex
 A large number of diseases may affect the adrenal cortex, including lymphomas,
amyloidosis,sarcoidosis, hemochromatosis, fungal infections, and adrenal
hemorrhage,
 >90% of all cases are attributable to one of four disorders: autoimmune
adrenalitis, tuberculosis, AIDS, or metastatic cancers
212

 Autoimmune adrenalitis- most common cause
 autoimmune destruction of steroidogenic cells.
 Autoantibodies to several key steroidogenic enzymes (21-hydroxylase,
17-hydroxylase) have been detected
Autoimmune polyendocrine syndrome type 1 (APS1)
 Characterized by chronic mucocutaneous candidiasis and
abnormalities of skin, dental enamel, and nails (ectodermal dystrophy)
in association with a combination of organ-specific autoimmune
disorders
213

 caused by mutations in the autoimmune regulator (AIRE) gene on
chromosome 21q22.
 In the absence of AIRE function, central T-cell tolerance to peripheral
tissue antigens is compromised, promoting autoimmunity
 develop autoantibodies against IL-17 and IL-22
Autoimmune polyendocrine syndrome type 2 (APS2)
 usually starts in early adulthood and presents as a combination of
adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes
214

 Primary autoimmune adrenalitis is characterized by irregularly shrunken
glands, which may be difficult to identify within the suprarenal adipose tissue
 Histologically the cortex contains only scattered residual cortical cells in a
collapsed network of connective tissue. A variable lymphoid infiltrate is present in
the cortex and may extend into the adjacent medulla, although the medulla is
otherwise preserved
215

 Addisons disease is characterized by the presence of
autoantibodies directed predominantly against 21-
hydroxylase.
 The myriad clinical manifestations of Addisons disease,
including muscle weakness and fatigue, hypotension and
hyponatremia, and loss of axillary and pubic hair in women,
are the result of cortisol, aldosterone and sex hormone
deficiencies, respectively.
217

 Vessel wall inflammation
 Vessels of any type in virtually any organ can be affected, but
most vasculitides affect small vessels
 The two common pathogenic mechanisms
 immune-mediated inflammation
 direct invasion of vascular walls by infectious pathogens
 Infections can also indirectly induce a noninfectious vasculitis
219

Noninfectious Vasculitis
 The major cause of noninfectious vasculitis is a local or
systemic immune response. Caused by:
 Immune complex deposition
 Antineutrophil cytoplasmic antibodies
 Antiendothelial cell antibodies
 Autoreactive T cells
221

Immune Complex-Associated Vasculitis:
 Seen in systemic immunologic disorders
 The vascular lesions resemble those immune complex–mediated disorders
 Immune complex deposition is also implicated in
 Drug hypersensitivity vasculitis- antibodies directed against the drugmodified
proteins or foreign molecules result in immune complex formation
 Vasculitis secondary to infections- Antibodies to microbial constituents can
form immune complexes that circulate and deposit in vascular lesions
222

 Antineutrophil Cytoplasmic Antibodies
223

 Myasthenia gravis is an autoimmune disease that is usually
associated with autoantibodies directed against acetylcholine
receptors
 Prevalence of 150 to 200 per million and shows a bimodal age
distribution.
 About 85% of patients have autoantibodies against postsynaptic
acetylcholine receptors
 Remaining patients have antibodies against the sarcolemmal
protein muscle-specific receptor tyrosine kinase
225

 Anti-acetylcholine receptor antibodies lead to the aggregation
and degradation of the receptors, and also to damage of the
postsynaptic membrane through complement fixation
 Autoantibodies directed against muscle-specific receptor
tyrosine kinase do not fix complement
 Antibodies seem to interfere with the trafficking and clustering of
acetylcholine receptor within the sarcolemmal membrane
226

LAMBERT-EATON MYASTHENIC SYNDROME
 Autoimmune disorder caused by antibodies that block acetylcholine release
by inhibiting a presynaptic calcium channel
 Present with weakness of their extremities
 In about half of cases there is an underlying malignancy, most often
neuroendocrine carcinoma of the lung
 Stimulus for autoantibody formation in paraneoplastic cases may be the
expression of the same calcium channel in the neoplastic cells
230

 Autoimmune disease in which islet destruction is caused primarily by
immune effector cells reacting against endogenous β-cell antigens
 Develops in childhood, becomes manifest at puberty, and progresses with
age
Pathogenesis-
 Genetic Susceptibility-
 Higher concordance rates for disease in monozygotic vs dizygotic twins
 genome-wide association studies have identified multiple genetic susceptibility loci
 the most important locus is the HLA gene cluster on chromosome 6p21
232

 Ninety percent to 95% have either an HLA-DR3 or HLA-DR4 haplotype
 40% to 50% of patients combined DR3/DR4 heterozygotes
 DR3 or DR4 concurrently with a DQ8 haplotype highest inherited risks for type 1
diabetes
 The first disease-associated non-MHC gene to be identified was insulin, with
variable number of tandem repeats (VNTRs) in the promoter region being
associated with disease susceptibility
 Environmental Factors-
 viral infections have been suggested as triggers
 viruses might share epitopes with islet antigens- Molecular mimicry
233

 Caused by antibodies that bind to red cells, leading to
their premature destruction.
 The diagnosis of immunohemolytic anemia requires the
detection of antibodies and/or complement on red cells from
the patient.
 Warm Antibody Type-
 Most common form
 Most causative antibodies are of the IgG class
 The red cell hemolysis is mostly extravascular
237

 IgG-coated red cells bind to Fc receptors on phagocytes, which remove red
cell membrane during “partial” phagocytosis
 The loss of membrane converts the red cells to spherocytes, which are
sequestered and destroyed in the spleen
 In many cases, the antibodies are directed against the Rh blood group
antigens
238

 The mechanisms of drug-induced immunohemolytic anemia
are better understood. Two different mechanisms have been
described.
 Antigenic drugs
 Tolerance-breaking drugs
239

Cold Agglutinin Type
 caused by IgM antibodies that bind red cells avidly at low
temperatures (0°C to 4°C)
 Cold agglutinin antibodies appear transiently following certain
infections,
 Mycoplasma pneumoniae
 Epstein-Barr virus
 Cytomegalovirus
 influenza virus
 human immunodeficiency virus (HIV)
240

Cold Hemolysin Type
 Cold hemolysins are autoantibodies
 Paroxysmal cold hemoglobinuria
 Rare disorder causes substantial, sometimes fatal, intravascular hemolysis and
hemoglobinuria
 The autoantibodies are IgGs that bind to the P blood group antigen on the red cell
surface in cool, peripheral regions of the body
241

Mechanisms of β Cell Destruction-
 The fundamental immune abnormality in type 1 diabetes
is a failure of self-tolerance in T cells specific for islet
antigens
 The activated T cells cause β-cell injury
 Multiple T-cell populations have been implicated in this
damage,
 TH1 cells (which may secrete cytokines, including IFN-γ and TNF,
that injure β cells)
 CD8+ CTLs (which kill β cells directly)
243

 The islet autoantigens that are the targets of immune attack may include insulin,
the β cell enzyme glutamic acid decarboxylase(GAD), and islet cell autoantigen
512 (ICA512)
 A role for antibodies in type 1 diabetes is suspected
 Autoantibodies against islet antigens are found in the vast majority of patients
 The presence of islet cell antibodies is used as a predictive marker for the disease
244

DIAGNOSIS
Tests that may be done to diagnose an autoimmune disorder
may include:
 Antinuclear antibody test.
 Complete blood count test.
 C-reactive protein.
 Erythrocyte sedimentation rate
246

Current Therapies
 Immunosuppressive drugs.
- corticosteroids, azathioprine
- slows the proliferation of lymphocytes
 Cyclosporin A.
- blocks signal transduction mediated by the TCR (inhibits only antigen-
activated T cells)
247

 Thymectomy
- removal of thymus from patients with myasthenia gravis
 Plasmapheresis
- removes antigen-antibody complexes for a short- term
-reduction in symptoms.
248

SUMMARY
 Autoimmune diseases and conditions exists when the body
produces abnormal cells, which attack the body, itself.
 Many biological, chemical , and environmental irritants may
play central role.
 There are five possible mechanism and collectively most of
the auto immune disorders can be classified into three class.
249

 Most autoimmune diseases strike women more often than
men.
 Strike any part of the body, symptoms vary widely and
diagnosis and treatment are often difficult.
 Medical science is striving to design therapies that prevent
autoimmune diseases.
250

Autoimmune disorders

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