SLESLE

Multisystem Autoimmune diseaseMultisystem Autoimmune disease

Failure to maintain self toleranceFailure to maintain self tolerance

GeneralGeneral

Unpredictable , remitting and relapsing Unpredictable , remitting and relapsing diseasedisease

Mainly affectsMainly affects1.1. Skin Skin 2.2. KidneyKidney3.3. Serosal membranesSerosal membranes4.4. JointsJoints5.5. HeartHeart

Due to APLA Due to APLA recurrent arterial and venous recurrent arterial and venous thrombosisthrombosis

ThrombocytopeniaThrombocytopenia Recurrent spontaneous miscarriagesRecurrent spontaneous miscarriages

DiagnosisDiagnosis

4 or more of the criteria duing any interval of 4 or more of the criteria duing any interval of the observationthe observation

Classically includin Anti Nuclear Anti bodyClassically includin Anti Nuclear Anti body

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 onset Age of onset 2 2ndnd to 3 to 3rdrd decades decades More common n black americansMore common n black americans

PathogenesisPathogenesis

Failure to maintain self toleranceFailure to maintain self tolerance

SnRNP –Smith AntigenSnRNP –Smith Antigen

snRNPsnRNPs (pronounced "snurps"), or s (pronounced "snurps"), or ssmall mall nnuclear uclear rriboibonnucleoucleopproteinsroteins, are , are RNARNA-protein complexes that -protein complexes that combine with unmodified combine with unmodified pre-mRNApre-mRNA and various and various other proteins to form a other proteins to form a spliceosomespliceosome, a large RNA-, a large RNA-protein molecular complex upon which protein molecular complex upon which splicingsplicing of of pre-mRNApre-mRNA occurs. The action of snRNPs is essential occurs. The action of snRNPs is essential to the removal of to the removal of intronsintrons from from pre-mRNApre-mRNA, a critical , a critical aspect of aspect of post-transcriptional modificationpost-transcriptional modification of RNA, of RNA, occurring only in the occurring only in the nucleusnucleus of of eukaryotic cellseukaryotic cells. .

RNPRNP

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

Most common method used is Indirect Most common method used is Indirect immunofluorescenceimmunofluorescence

1.1. Rim or peripheral staining Rim or peripheral staining ds DNA ds DNA

2.2. Speckled appearance Speckled appearance Histones and Histones and RibonucleoproteinsRibonucleoproteins

3.3. Homogenous / Diffuse Homogenous / Diffuse to both to both

4.4. Discrete spots within nuclues Discrete spots within nuclues Nucleolar Nucleolar

APLA APLA Prothrombin is a phospholipid Prothrombin is a phospholipid It is a hypercoagulable state invivoIt is a hypercoagulable state invivo Intereferance with endothelial cell production Intereferance with endothelial cell production

of PGI 2of PGI 2

Renal changes in SLE/Lupus NephritisRenal changes in SLE/Lupus Nephritis

Class 1 Class 1 < 5% < 5% Normal by Light ,electron Normal by Light ,electron and immunoand immuno

Class 2Class 2 10 -25% 10 -25% Mesangeal Lupus GNMesangeal Lupus GN Class 3 Class 3 20 – 35 % 20 – 35 % Focal Proliferative Focal Proliferative

GNGN Class 4 Class 4 35 – 60% 35 – 60% Diffuse Porliferative Diffuse Porliferative

GNGN Class 5 Class 5 10 – 15 % 10 – 15 % Membraneous GN Membraneous GN Class 6 Class 6 Advanced Sclerosing GN Advanced Sclerosing GN

Skin changesSkin changes

SpleenSpleen

Capsular fibrous thickeningCapsular fibrous thickening Follicular hyperplasiaFollicular hyperplasia Numerous plasma cells in red pulpNumerous plasma cells in red pulp Central penicillary arteries show thickening Central penicillary arteries show thickening

and perivascular fibrosis producing ONION and perivascular fibrosis producing ONION SKIN lesionsSKIN lesions

Here are flat, pale tan, spreading vegetations over the Here are flat, pale tan, spreading vegetations over the mitral valve surface and even on the chordae mitral valve surface and even on the chordae tendineae. This patient has systemic lupus tendineae. This patient has systemic lupus erythematosus. Thus, these vegetations that can be on erythematosus. Thus, these vegetations that can be on any valve or even on endocardial surfaces are any valve or even on endocardial surfaces are consistent with Libman-Sacks endocarditis. These consistent with Libman-Sacks endocarditis. These vegetations appear in about 4% of SLE patients and vegetations appear in about 4% of SLE patients and rarely cause problems because they are not large and rarely 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 remote and fused chordae tendineae that represent remote rheumatic heart disease. rheumatic heart disease.

Two light-yellow verrucae can be seen on the Two light-yellow verrucae can be seen on the endocardium of the left ventricle immediately endocardium of the left ventricle immediately beneath the insertions of chordae tendineae to beneath the insertions of chordae tendineae to the mitral valve. These rather characteristic the mitral valve. These rather characteristic vegetations (Libman-Sacks) are not found in vegetations (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 found When 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 systolic This type of endocarditis can cause systolic heart murmurs. heart murmurs.