Lupus Flashcards
definition of systemic lupus erythematosus
a systemic autoimmune disease characterized by the production of antibodies to the components of a cell nucleus in association with protean clinical manifestations
criteria for SLE
> 4 criteria fulfilled. Must have at least one clinical and one lab OR biopsy proven lupus nephritis with positive ANA or anti-DNA
clinical criteria for SLE
malar rash, discoid rash, oral/nasal ulcers, non-scarring alopecia, arthritis, serositis, renal, neurologic, hemolytic anemia, thrombocytopenia, leucopenia
immunologic criteria for SLE
ANA (anti nuclear antibody), anti-dsDNA, Anti-Smith, anti phospholipid antibodies, low complement levels (C3,4), positive direct coombs test
malar rash
acute cutaneous lupus, butterfly rash die to photosensitivity. Cheeks and nose. Non-scarring.
Discoid lupus
chronic cutaneous lupus, red raised disc shaped patches. can be anywhere on body. scarring.
alopecia in lupus
diffuse thinning or hair fragility with visible broken hairs, in the absence of other causes
arthritis in lupus
tends to be non-erosive (jacoud’s: erosion of MC heads and ulnar deviation)
serositis in lupus
inflammation around the lining of the lung or heart that causes chest pain when taking a deep breath. Lung=pleuritis, heart=pericarditis
nephritis in lupus
protein in urine (>500mg/24hrs) &/or red cell casts
red cell casts
red cells from the glomerulus of the kidney surrounded by a proteinacious matrix, indicative of inflammation and damage to the kidney
neurologic symptoms of lupus
seizures, psychosis, myelitis (cerebritis)
hematologic symptoms of lupus
hemolytic anemia (coombs positive), leukopenia or lymphopenia, thrombocytopenia
lupus epidemiology
females:male=15:1, can present at any age. children/men tend to be more severe, uncommon in europeans/africans,
why are women more affected by lupus?
X chromosome may contribute? pregnant lupus patients have less of an estrogen/progesterone surge during late trimesters, UNKNOWN
genetics of lupus
cumulative effect of several genes is necessary, very heterogenous
environmental factors for lupus
viruses like EBV (molecular mimicry?), UV light (increased cytokines?), smoking
autoantibodies
antibodies that recognize self antigens generated during antibody assembly and pass through defective check point system. LOSS OF SELF TOLERANCE
pathway of self antigen presentation
APCs are hyper activated by environmental, viral or other trigger, so they phagocytose self antigen and are activated. They then present self-antigen to host lymphocytes which should have been killed during development
ANA
anti-nuclear antibodies that bind to antigens found in the nucleus of the cell.
how to measure ANAs?
indirect immunofluorescence & ELISA. HEp2 cells are coated with patient serum and Ab:Ag complexes are detected via anti-human fluorescence labeled antibodies. Serial dilutions tested to determine titer volume of antibodies
HEp2 cells
immortalized laryngeal epidermoid carcinoma cells
anti dsDNA
specific for SLE and titer fluctuates with disease activity. associated with active glomerulonephritis, perinuclear ANA fluorescent pattern
Anti Smith (SM)
specific for SLE, Speckled ANA fluorescent pattern
anti-RNP
seen in both SLE and mixed connective tissue disease
Anti-Ro/La (SSA/SSB)
seen in SLE and with Sjogrens Syndrome and pathogenic in neonatal lupus.
antiphospholipid antibodies
antibody to phospholipid part of cell membrane thought to make blood more susceptible to clotting, causing clots in arteries, veins, and increased risk of miscarriage
possible pathogenic mechanisms for SLE
apoptosis, immune complex deposition, cytokine production, T cells
abnormal apoptosis in SLE
self antigens are normally recognized when cells apoptose, but in SLE phagocytosis and IC clearing is defective due to deficient Fc and complement receptors
when do nuclear antigens present?
appear within apoptotic blebs or are released during blebbing. impaired phagocytosis leads to persistence of antigen and immune complexes
apoptotic blebbing
main phagocytic targets
neonatal lupus
mother’s anti-Ro/La crosses the placenta and gets into the fetal circulation and binds fetal myocardiocyte after blebs containing Ro antibody are exposed, causing inflammation and cell death. manifests as conduction abnormality and causes death in utero.
immune complex deposition
IC activates complement system, which causes recruitment of inflammatory cells, IC gets phagocytosed and additional mediators of inflammation are released.
where do ICs deposit?
depends on size and charge
complement levels in SLE
the lower the complement (C3/4), the higher the disease activity because consumption indicates IC clearing
cytokines important in lupus
Interferon and BLyS
TLRs of SLE
7/9. activated by ICs to stimulate dendritic cells, which then release type 1 interferons
type 1 IFNs
first responder to infection, potent promoter of inflammatory response and promotes survival of auto reactive B cells. higher level=increased disease activity
BLyS (BAFF)
B lymphocyte stimulator, promotes increase B cell survival.
anti-BLyS antibody?
Belimumab (Benlysta). targeted monoclonal antibody that binds to soluble BLyS, allowing more B cells to undergo apoptosis, preventing survival of auto reactive B cells
how t cells cause damage in lupus
stimulate autoreactive b cells via cytokines, can also directly damage tissues (CTL)
