Genetic Susceptibility MHC Related Not mhc related HLA-DR1, 2, 3, 4 C1q deficiency(rare but highest risk Alleles of HLA-DRB1 IRF5 Chromosome 1 region 1q41-43(PARP), and stat4 region 1q23(FcYRIIA, FcYRIIIA C2-C4 deficiency IL-10, IL-6 and MBL polymorphisms TNF-a polymorphisms Chromosome 8.p23.1: reduced expression of blk and increased expression of C8orf13(B cell tyrosine kinase), chromosome 16p11.22: integrin a genes IGAM-ITGAX B cell gene BANK1 x chromosome-linked gene IRAK1
Genetic Susceptibility MHC Related • HLA-DR1, 2, 3, 4 • Alleles of HLA-DRB1, IRF5, and STAT4 • C2 - C4 deficiency • TNF- polymorphisms Not MHC Related • C1q deficiency (rare but highest risk) • Chromosome 1 region 1q41-43 (PARP), region 1q23 (FcγRIIA, FcγRIIIA) • IL-10, IL-6 and MBL polymorphisms • Chromosome 8.p23.1: reduced expression of BLK and increased expression of C8orf13 (B cell tyrosine kinase), chromosome 16p11.22: integrin genes IGAM-ITGAX • B cell gene BANK1 • X chromosome-linked gene IRAK1
Environmental factors Some environmental factors which may trigger the disease include >Infections > certain drugs ultraviolet light >extreme stress > hormones
Environmental factors • Some environmental factors which may trigger the disease include : Infections certain drugs ultraviolet light extreme stress hormones
Infections o There has been continuing interest in the possibility that infectious agents might initiate or flare sle o Mechanism might include molecular mimicry between external Ag and a self-Ag, epitope spreading nonspecific activation of t or b cells There has been recent interest in Eb. cmv and other VIrus
Infections There has been continuing interest in the possibility that infectious agents might initiate or flare SLE. Mechanism might include molecular mimicry between external Ag and a self-Ag, epitope spreading, nonspecific activation of T or B cells. There has been recent interest in EB, CMV and other virus
Drugs Drug-induced lupus. Drugs( hydralazine, procainamide, beta blokes, isoniazid, penicillamine, sulfa) can induce lupus Drug-induce lupus may resemble sle both clinically and serologically e Usually the disease is mild, renal and neurological complications are rare Generally, lupus that is caused by a drug exposure goes away once the drug is stopped
Drugs Drug-induced lupus. Drugs ( hydralazine, procainamide, betablokers, isoniazid, penicillamine, sulfa) can induce lupus. Drug-induce lupus may resemble SLE both clinically and serologically. Usually the disease is mild, renal and neurological complications are rare. Generally, lupus that is caused by a drug exposure goes away once the drug is stopped
Ultraviolet light e UV light, especially UVB, flares SLE in most patients o It is unclear whether exposure to UV light can initiate the lupus but onset after a sunburn is not unusual o There is good evidence that exposure of skin to UV light alters the location and chemistry of dna as well as the availability of ro and rnp antigens
Ultraviolet light UV light, especially UVB, flares SLE in most patients. It is unclear whether exposure to UV light can initiate the lupus, but onset after a sunburn is not unusual. There is good evidence that exposure of skin to UV light alters the location and chemistry of DNA as well as the availability of Ro and RNP antigens