This document discusses multisystem autoimmune disease, also known as systemic lupus erythematosus (SLE). SLE is characterized by the failure to maintain self-tolerance, resulting in an unpredictable and relapsing disease that commonly affects the skin, kidneys, serosal membranes, joints, and heart. Diagnosis requires 4 of several criteria during any observation period, and it is more common in women and black Americans. The pathogenesis involves abnormal self-reactive antibodies against nuclear and cytoplasmic antigens such as Sm/RNP and dsDNA. Complications can include renal disease, skin changes, splenic abnormalities, and Libman-Sacks endocarditis - characterized by nonbacterial vegetations in the heart

1. SLESLE
Multisystem Autoimmune diseaseMultisystem Autoimmune disease
Failure to maintain self toleranceFailure to maintain self tolerance

2. GeneralGeneral
 Unpredictable , remitting and relapsingUnpredictable , remitting and relapsing
diseasedisease
 Mainly affectsMainly affects
1.1. SkinSkin
2.2. KidneyKidney
3.3. Serosal membranesSerosal membranes
4.4. JointsJoints
5.5. HeartHeart

3.  Due to APLADue to APLA  recurrent arterial and venousrecurrent arterial and venous
thrombosisthrombosis
 ThrombocytopeniaThrombocytopenia
 Recurrent spontaneous miscarriagesRecurrent spontaneous miscarriages

6. DiagnosisDiagnosis
 4 or more of the criteria duing any interval of4 or more of the criteria duing any interval of
the observationthe observation
 Classically includin Anti Nuclear Anti bodyClassically includin Anti Nuclear Anti body

7. EpidemiologyEpidemiology
 F: m = 9: 1F: m = 9: 1
 1 in 700 women in child bearing age group1 in 700 women in child bearing age group
 Age of onsetAge of onset  22ndnd
to 3to 3rdrd
decadesdecades
 More common n black americansMore common n black americans

8. PathogenesisPathogenesis
 Failure to maintain self toleranceFailure to maintain self tolerance

9. SnRNP –Smith AntigenSnRNP –Smith Antigen
 snRNPsnRNPs (pronounced "snurps"), ors (pronounced "snurps"), or ssmallmall nnuclearuclear
rriboibonnucleoucleopproteinsroteins, are, are RNARNA-protein complexes that-protein complexes that
combine with unmodifiedcombine with unmodified pre-mRNApre-mRNA and variousand various
other proteins to form aother proteins to form a spliceosomespliceosome, a large RNA-, a large RNA-
protein molecular complex upon whichprotein molecular complex upon which splicingsplicing ofof
pre-mRNApre-mRNA occurs. The action of snRNPs is essentialoccurs. The action of snRNPs is essential
to the removal ofto the removal of intronsintrons fromfrom pre-mRNApre-mRNA, a critical, a critical
aspect ofaspect of post-transcriptional modificationpost-transcriptional modification of RNA,of RNA,
occurring only in theoccurring only in the nucleusnucleus ofof eukaryotic cellseukaryotic cells..

10. RNPRNP
 Ribonucleoprotein (RNP)Ribonucleoprotein (RNP) is ais a nucleoproteinnucleoprotein
that containsthat contains RNARNA, i.e. it is an association that, i.e. it is an association that
combinescombines ribonucleic acidribonucleic acid andand proteinprotein
together. A few known examples include thetogether. A few known examples include the
ribosomeribosome, the enzyme telomerase, vault, the enzyme telomerase, vault
ribonucleoproteins, and small nuclear RNPsribonucleoproteins, and small nuclear RNPs
(snRNPs), which are implicated in pre-mRNA(snRNPs), which are implicated in pre-mRNA
splicing and are among the main componentssplicing and are among the main components
of the nucleolus.of the nucleolus.

12.  Most common method used is IndirectMost common method used is Indirect
immunofluorescenceimmunofluorescence
1.1. Rim or peripheral stainingRim or peripheral staining  ds DNAds DNA
2.2. Speckled appearanceSpeckled appearance  Histones andHistones and
RibonucleoproteinsRibonucleoproteins
3.3. Homogenous / DiffuseHomogenous / Diffuse  to bothto both
4.4. Discrete spots within nucluesDiscrete spots within nuclues  NucleolarNucleolar

14.  APLAAPLA  Prothrombin is a phospholipidProthrombin is a phospholipid
 It is a hypercoagulable state invivoIt is a hypercoagulable state invivo
 Intereferance with endothelial cell productionIntereferance with endothelial cell production
of PGI 2of PGI 2

15. Renal changes in SLE/Lupus NephritisRenal changes in SLE/Lupus Nephritis
 Class 1Class 1  < 5%< 5%  Normal by Light ,electronNormal by Light ,electron
and immunoand immuno
 Class 2Class 2 10 -25%10 -25% Mesangeal Lupus GNMesangeal Lupus GN
 Class 3Class 3  20 – 35 %20 – 35 % Focal ProliferativeFocal Proliferative
GNGN
 Class 4Class 4  35 – 60%35 – 60% Diffuse PorliferativeDiffuse Porliferative
GNGN
 Class 5Class 5  10 – 15 %10 – 15 %  Membraneous GNMembraneous GN
 Class 6Class 6  Advanced Sclerosing GNAdvanced Sclerosing GN

16. Skin changesSkin changes

17. SpleenSpleen
 Capsular fibrous thickeningCapsular fibrous thickening
 Follicular hyperplasiaFollicular hyperplasia
 Numerous plasma cells in red pulpNumerous plasma cells in red pulp
 Central penicillary arteries show thickeningCentral penicillary arteries show thickening
and perivascular fibrosis producing ONIONand perivascular fibrosis producing ONION
SKIN lesionsSKIN lesions

20.  Here are flat, pale tan, spreading vegetations over theHere are flat, pale tan, spreading vegetations over the
mitral valve surface and even on the chordaemitral valve surface and even on the chordae
tendineae. This patient has systemic lupustendineae. This patient has systemic lupus
erythematosus. Thus, these vegetations that can be onerythematosus. Thus, these vegetations that can be on
any valve or even on endocardial surfaces areany valve or even on endocardial surfaces are
consistent with Libman-Sacks endocarditis. Theseconsistent with Libman-Sacks endocarditis. These
vegetations appear in about 4% of SLE patients andvegetations appear in about 4% of SLE patients and
rarely cause problems because they are not large andrarely cause problems because they are not large and
rarely embolize. Note also the thickened, shortened,rarely embolize. Note also the thickened, shortened,
and fused chordae tendineae that represent remoteand fused chordae tendineae that represent remote
rheumatic heart disease.rheumatic heart disease.

22.  Two light-yellow verrucae can be seen on theTwo light-yellow verrucae can be seen on the
endocardium of the left ventricle immediatelyendocardium of the left ventricle immediately
beneath the insertions of chordae tendineae tobeneath the insertions of chordae tendineae to
the mitral valve. These rather characteristicthe mitral valve. These rather characteristic
vegetations (Libman-Sacks) are not found invegetations (Libman-Sacks) are not found in
most hearts from lupus patients at autopsy.most hearts from lupus patients at autopsy.
When present, they are most commonly foundWhen present, they are most commonly found
under the tricuspid and mitral valve leaflets.under the tricuspid and mitral valve leaflets.
This type of endocarditis can cause systolicThis type of endocarditis can cause systolic
heart murmurs.heart murmurs.