lupus Flashcards
SLE: Loss of tolerance to ______ leads to immune system mediated damage to self
self
SLE is rarer than RA?
yep At most one hundredth of RA
Female predominance (7-15:1) In children and older lupus populations this ratio is not as high.
Increased frequency in close relatives
30-50% concordance in monozygotic twins
Ethnic and racial susceptibilities may support genetic influence
HLA-DR2 and –DR3: weak associations
STAT4 (a transcription factor) gene variant allele on chromosome 2 confers increased risk of rheumatoid arthritis and SLE
genetic factors of SLE
SLE central defect
apoptosis
Increased frequency in close relatives
30-50% concordance in monozygotic twins
Ethnic and racial susceptibilities may support genetic influence
HLA-DR2 and –DR3: weak associations
STAT4 (a transcription factor) gene variant allele on chromosome 2 confers increased risk of rheumatoid arthritis and SLE
_____________ activation and its activation of the innate immune response may play a central role in perpetuating the autoreactive immune response
Toll-like receptor
A strong ___________ is a hallmark of the cytokine profile in SLE. Mimics what might be seen in a chronic viral infection
interferon-1 induced gene transcript signature (with IFN-α the dominant mediator)
SLE _________ serum complement levels are a marker for disease activity (particularly C3 and C4)
decreased
Activates complement cascade so abundantly that one sees complement depleted/consumed faster than it can be made
SLE marker for disease activity
Anti-dsDNA
most specific ab but no correlation with disease activity
anti-Sm(ith)
Anti SSA (Ro), -SSB (La)
seen in both SLE and sjorgen
Tregs cells are diminished in number and activity
yea
Anti-RNP –
seen in SLE and “mixed connective tissue disease”
Antiphospholipid antibodies (APLA)
when pathogenic - thrombosis, fetal loss
Anticardiolipin, lupus anticoagulant, false + VDRL all represent APLA
Immune complexes in SLE
deposition in vessels and tissues initiates inflammation leading to damage
Constitutional symptoms – nonspecific but can be profound (which do we see?) Fatigue Weight loss Fever, sweats, chills Lymphadenopathy
all of these can be seen in SLE
Inflamation of muscles with release of muscle enzymes. Only rarely progresses to actual weakness thus usually a laboratory finding (elevation of creatine phosphokinase)
Myositis –
cutaneous manifestations
- malar rash- in 50% brought on by photosensitive, transient or chronic and similar appearing rashes seen in pregnancy
- photosensitivity- 50%
- discoid annular scaly plaques; scarring , head and neck arms
- subacute cutaneous lupus- small erythematous papules that coalesce into patterns; nonscarring
- bullous lupus rashes
- alopecia
- vascular- raynaud’s, telangiectasia
. Deposits of multiple immune elements such as complement components and immunoglobulins (eg: IgM, IgG, etc)) may be found at the dermal-epidermal juncture
Positive lupus band test in SLE skin
Probably the most morbid manifestation of SLE. This used to be a major cause of mortality in the pre-steroid era.
lupus nephritis
Nearly all patients have EM and immunofluorescent renal abnormalities; 50% have clinically apparent disease.
Usually but not always occurs in the first years of the disease.
what happens in lupus nephritis?
immune complexes and complement deposit in glomeruli in capillary wall, subepithelium, subendothelium, and mesangium invoking inflammation and cellular proliferative and fibrotic (scarring) response
Urinary findings in lupus nephritis:
- what type of cells do we see?
- is there protein in the urine?
- Casts?
Hematuria (RBC) > pyuria (WBC)
Proteinuria
Casts – RBC casts most ominous
class II GN
mesangial proliferative GN
Class III GN
focal proliferative GN
Class IV GN
diffuse proliferative GN
