Trauma-Informed Leadership - Five Practical Principles
AUTOIMMUNITY PART 2 SYSTEMIC LUPUS ERYTHEMATOSUS
1. PA9.5
DEFINE & DESCRIBE THE
PATHOGENESIS OF SLE
Dr IRA BHARADWAJ
MCI TEACHER ID: PAT 2300569
KUHS FACULTY ID: M21512
2. TEXT BOOK REFRENCES
• ROBBINS BASIC PATHOLOGY
• HARSH MOHAN TEXTBOOK OF PATHOLOGY
• DAVIDSON’S PRINCIPLES AND PRACTISE OF MEDICINE
• OTHER STANDARD REFRENCES
3. SLO
• DEFINITION OF SLE
• ETIOPATHOGENESIS OF SLE – GENETIC & ENVIORNMENTAL
FACTORS
• MORPHOLOGY OF SLE – KIDNEY & OTHER ORGANS
• CLINICAL FEATURES, PROGNOSIS & TREATMENT OF SLE
• QUESTIONS AT END OF SECTION 9.7
4. SYSTEMIC LUPUS ERYTHEMATOSUS
DEFINITION
• SLE IS A MULTISYSTEM
• AUTOIMMUNE DISEASE
• OF PROTEAN MANIFESTATIONS & VARIABLE CLINICAL BEHAVIOUR
• CHARACTERIZED BY PRESENCE OF LARGE NUMBER & TYPES OF
AUTOANTIBODIES, SPECIALLY ANTI NUCLEAR ANTIBODIES [ANA]
• THERE ARE TWO VARIANTS – SYSTEMIC [AFFECTING MULTIPLE ORGANS]
AND DISCOID AFFECTING SKIN ONLY
5. SYSTEMIC LUPUS ERYTHEMATOSUS
ETIOPATHOGENESIS
GENETIC FACTORS
• 9:1 (f:m)
• Black American [more common]
• Familial predisposition (20% unaffected relatives of patient
have ANA)
• HLA-DR2/DR3
• Genetic defect of classical complement pathway proteins
• Inadequate control of BL activation (inhibitory Fc receptor
defect)
6. SYSTEMIC LUPUS ERYTHEMATOSUS
ETIOPATHOGENESIS
ENVIRONMENTAL FACTORS
• UV exposure
• Smoking
• Sex hormones (10 X more in reproductive age)
• Drugs (procainamide & hydralazine) – affect demethylation of
DNA – altered expression of genes in immunity.
7. SLE
IMMUNOLOGICAL ABNORMALITIES
INNATE IMMUNITY
• Type I interferon (IFN a) secretion increased by dendritic cells
[IFR5 gene]
• Increase in TLRs – present on macrophages, NK, neutrophils,
mucosal cells (bind toll Ags on bacteria, induce infl’ via TNF,
IL-I, & other cytokines, & activate BL)
• Increased immunological reactivity to nucleoproteins
ADAPTIVE IMMUNITY
• Failure of B L tolerance
8. SLE
PATHOGENESIS OF IMMUNOLOGICAL ABNORMALITIES
INCREASED APOPTOSIS DUE TO ENVIRONMENTAL CAUSES,
FOLLOWED BY:
• Decreased clearance of apoptotic cells,
• Exposure of immune system to nuclear Ags,
• Development of autoantibodies [ANA] which lead to
• Inflammation & necrosis [type 2 & 3 hypersensitivity
reactions] again followed by
• Decreased clearance of necrotic cells & increase in nuclear
Ags and increase in ANAs [anti nuclear antibodies]
9. Ig G antibody to nuclear & other self proteins
Type 2 & 3 hypersensitivity reactions
Clinical manifestations.
Environmental triggers Nucleosome proteins &
UV, smoking, hormones, drugs other self antigens
Activation of helper T cells & increase in INF-a & TLR &
failure of BL self tolerance
Genetically susceptible individual
Genes involved:
F>M, family history
MHC class - II HLA DR 2&3
Complement defects
inhibitory function of BL defect
10.
11. ANTIBODIES IN SLE
ANA [anti nuclear antibodies]
• anti-dsDNA [double strand DNA]
• anti-Sm (ribonuclear core protein, Sm ag),
• anti-RNP UI
• anti-histone,
• anti-SS-A, anti-SS-B (ribonucleoprotein)
12. ANTIBODIES IN SLE
OTHER Abs-
• Against RBC, platelets, lymphocytes
• APL (antiphospholipid antibody)
• These antibodies are detected by IFA, ELISA & flow cytometer
• False positive test is seen in other autoimmune diseases,
malignancy and chronic infections
13. SLE
MECHANISM OF TISSUE INJURY
TYPE II HYPERENSITIVITY REACTIONS
• Abs (IgG & IgM ) bind to Ags on cell surface ,
• This activates phagocytes, complement, ADCC ( Ab
dependent cellular cytotoxicity ) mediated by NK cells,
monocytes, neutrophils, eosinophils in fixed tissues and
• Cell death - lysis of RBS, WBC,& platelets in circulation
14. TYPE II- ANTIBODY MEDIATED HYPERSENSTIVITY
ROLE IN PATHOGENESIS OF SLE
15. SLE
MECHANISM OF TISSUE INJURY
ANTIPHOSPHOLIPID Ab COMBINE WITH PHOSPHOLIPIDS,
LEADING TO:
• Coagulation disorders, like increased thrombosis
• Abortions
• Reaction with CNS receptors, causing neuropsychiatric
symptoms
16. SLE
MECHANISM OF TISSUE INJURY
TYPE III HYPERSENSITIVITY REACTION
• ANA+EXPOSED NUCLEOPROTEIN form Ag-Ab complexes,
which are deposited in tissues, depending on several factors
• INFLAMMATION in tissues occurs due to
• Complement activation, which promotes inflammation &
necrosis
• Platelet activation & Hageman factor ( f xii) activation - micro
thrombi – ischemia- necrosis - inflammation
18. SLE
MORPHOLOGY
• Highly variable, depend on tissue involved & duration
• Acute necrotizing (fibrinoid necrosis) vasculitis, with fibrosis
& luminal narrowing is seen in all affected tissues
KIDNEY
• GLOMERULONEPHRITIS ( LUPUS NEPHRITIS )- deposit of
DNA- Anti-DNA & COMPLEMENT– EM, IFA, six classes (types)
• TUBULAR, INTERSTIAL lesions are also seen
19. LUPUS NEPHRITIS [LN]
• CLASS I – MINIMAL MESANGIAL LN shows IC [immune
complex] deposits on EM [electron microscopy] &
immunofluorescence [IF]. Light microscopic changes nil.
• CLASS II – MESANGIAL PROLIFERATIVE LN- mild to moderate
increase in mesangial matrix & cellularity
• CLASS III – FOCAL LN- < half glomeruli are affected by
swelling & proliferation of endothelial & mesangial cells,
neutrophilic infiltration, fibrinoid deposits & capillary
thrombi
20. LUPUS NEPHRITIS [LN]
• CLASS IV – DIFFUSE LN -> 50% GLOMERULI ARE INVOLVED,
proliferation of endothelial & mesangial cells – narrowing of
Bowman’s space, subendothelial deposit of immune
complexes – thickening of vessel wall (PAS stain)
• CLASS V – MEMBRANOUS LN – thickening of BM due to
deposition of IC & basement like material
• CLASS VI – ADVANCED SCLEROSING LN – complete sclerosis
(fibrosis) of glomeruli
21. SLE
MORPHOLOGY
SKIN: LESIONS ARE SEEN IN SLE AS WELL AS LOCALIZED FORM
KNOWN AS DISCOID LE [limited to skin only]
• Erythematous/maculopapular rash on malar eminences &
bridge of nose (butterfly rash, very characteristic of the
disease) & trunk and limbs
• Photosensitivity
• Dermo epidermal junction shows edema, lysis, inflammation,
immune complex [IC] deposits
26. SLE
C/F
• ARTHRITIS- nonerosive, involving peripheral joints like hands,
wrist, knee, elbow, feet, ankles
• HEMATOLOGICAL- pancytopenia of varying intensity
• CARDIAC- all layers of heart are affected, ischemic heart
disease [IHD]
• SEROSITIS – pleuritis, pericarditis
• INCREASED incidence of INFECTIONS
27. SLE
LAB DIAGNOSIS
SPECIFIC
• Anti Nuclear Antibodies [ANA],
anti ds DNA [double stranded DNA antibody] is
most specific
• RENAL BIOPSY shows features as described, EM &
immunofluorescence are very specific
• NONSPECIFIC – anemia, pancytopenia, raised ESR
28. SLE
LE CELL
LE CELL IS OF HISTORICAL IMPORTANCE ONLY
IT IS NO LONGER USED AS A DIAGNOSTIC TEST
LE cell test: In vitro test
• Blood is traumatized to expose the nuclei of leucocytes to
ANAs in circulation by
• Mixing the blood with glass beads & agitating it every half an
hour for 2 -3 hours.
29. SLE
LE CELL
LE CELL IS OF HISTORICAL IMPORTANCE ONLY
• Then the blood is centrifuged (after removing the glass
beads) and
• Buffy coat smear is prepared and the slide stained with
Leishman’s stain.
• The ANA-coated denatured nucleus (LE body) is chemotactic
for phagocytic cells, and it is seen as acellular amorphous
eosinophilic mass in neutrophil / monocyte
30. SLE
LE CELL
Typical LE cells has rounded
mass of amorphous nuclear
material (LE body) which may
displace the lobes of neutrophil
to the rim of the cell.
LE cell test is positive in 70%
cases of SLE
Other conditions with positive
LE test are: Rheumatoid arthritis,
Lupoid hepatitis , Penicillin
sensitivity.
31. SLE
TREATMENT & PROGNOSIS
• STEROIDS are useful in controlling the inflammation
• SPECIFIC B L DELETION THERAPY
• COURSE OF DISEASE IS MARKED BY REMISSION &
EXACERBATION
• DEATH IS USUALLY DUE TO RENAL FAILURE, INFECTION &
CADRIOVASCULAR DISEASE
• COMPLICATIONS SEEN MOST FREQUENTLY ARE INFECTIONS
& LYMPHOMA
