SLE Flashcards
(39 cards)
- an autoimmune disease in which organs and cells undergo damage initially
mediated by tissue-binding autoantibodies and immune complexes - Ninety percent of patients are women of child-bearing years
- highest prevalence is in African-American and Afro-Caribbean women, and lowest prevalence is in white men
SLE
- Inducing activation of innate immunity
Autoimmunity
is a genetic “signature” in peripheral blood cells 4 of 50-80% of SLE patients
Upregulation of genes induced by IFNs
-present antigen and secrete IL6 and IL10, further promoting autoreactive cell survival
- favored by estrogen
B cell
reduced capacity to clear immune complexes, apoptotic cells, and their DNA/RNA/ Ro/La and phospholipid containing surface blebs
Lupus phagocytic cells
destruction mediated by complement activation and release of
cytokines/chemokines
Deposition of autoantibodies and/or immune complexes
PREDISPOSING FACTORS
GENES
- High Hazard Ratios (268);
+ Deficiencies of C1q, C2,C4 (rare)
+ TREX1 mutations affecting DNA
degradation (rare) - Affecting Ag presentation or persistence,
e.g., phagocytosis of immune complexes
+ HLA-DRB1 (*1501,°0301), ORS, DQOA2
+ CR2, FCGR2A/8 - Enhance Innate Immunity, including production of IFNs
+ TNFEFAIPS, IRFS/TNPOS, IRF7/PHRF1, ITGAM, ICAMs - Alter Adaptive Immunity B and/or T Cell Signaling
+ BANK1, STAT4, MSHS, IZKF3, TCF7
PREDISPOSING FACTORS
GENES FOR LUPUS NEPHRITIS
- HLA-DRS,
- STAT4,
- APOL1 (African Americans),
- FCGRBA,
- ITGAM,
- IRFS,
- IRF7,
- TNFSF4 (Ox40L),
- DNAse
PREDISPOSING FACTORS
ENVIRONMENT/ MICROENVIRONMENT
- Ultraviolet Light,
- Smoking.
- Crystalline Silica,
- EBV infection
- Femaleness
PREDISPOSING FACTORS
EPIGENETICS
- Hypomethylation of DONA: In CD4+T, B and monocytes
- Some affect IFN production
- Histone modifications: Some increase expression of predisposing genes and/or IFN production
- MicroRNaA affecting gene expression
is permissive for SLE
Female sex
Women exposed to ___ have an increased risk of developing SLE
estrogen-containing oral contraceptives or hormone replacement
binds to receptors on T and B lymphocytes, increasing activation and survival of those cells, especially autoreactive subsets, thus favoring prolonged immune responses
Estradiol
Genes on the X chromosome that influence SLE, such as ___, may play a role in gender predisposition
TREX-1
Most SLE patients have autoantibodies for ___ before the first symptoms of disease, suggesting that regulation controls the degree of
autoimmunity for years before quantities and qualities of autoantibodies, pathogenic B and T cells, and activated tissue-fixed cells such as macrophages cause clinical disease
3 years or more
Exposure to ___causes flares of SLE in ~70% of patients
ultraviolet light
may be one infectious
agent that can trigger SLE in susceptible
individuals
Epstein Bar Virus (EBV)
increases risk
for SLE
- Current tobacco smoking
- Prolonged occupational exposure to crystalline silica
reduces the risk of SLE
Drinking alcohol (2 glasses of wine a week or 1/2 of an alcoholic drink daily)
Any combination of____ in the clinical and one in
the immunologic category, well documented at any time during an individual’s history, makes it likely that the patient has SLE
four or more criteria,
with at least one
___ of patients have either continuing active disease (on current treatment) or one or more flares of active disease annually
85%
are present most of the time
fatigue, myalgias/arthalgia
varying from mild to _ disabling, characterized by soft tissue swelling and tenderness in joints and/or tendons, most commonly in hands, wrists, and knees
intermittent polyarthritis
rheumatoid-like arthritis with erosions and fulfill criteria for both RA and SLE
Rhupus
