复旦大学：《内科学 Internal Medicine MBBS》课程教学资源（课件讲稿）重症监护医学_Systemic Lupus Erythematosus（二）

Systemic Lupus erythematosus XUE Yu Department of Rheumatology Huashan Hospital, Fudan University June 5th. 2012

Systemic Lupus Erythematosus XUE Yu Department of Rheumatology Huashan Hospital，Fudan University June 5th, 2012

Introduction Systemic lupus erythematosus( sLE is a chronic autoimmune disease that can be fatal however with recent medical advances fatalities are becoming increasingly rare. The immune system attacks the body' s cells and tissue resulting in inflammation and tissue damage SLE can affect any part of the body, but most often harms the heart. joints, skin, lungs, blood vessels, liver, kidneys, and nervous system Lupus can occur at any age, and is most common in women, particularly 90%of patients are women of child-bearing age

Introduction • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can be fatal; however, with recent medical advances, fatalities are becoming increasingly rare. • The immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage. • SLE can affect any part of the body, but most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. • Lupus can occur at any age, and is most common in women, particularly 90% of patients are women of child-bearing age

Epidemiology Incidence: 1 in 1. 000-10.000 Female to male ratio: 9-1 More common in African-Americans but it affects all races Mean age of onset: 28 years Positive family history in 10-15% of patients Monozygotic twins exhibit a greater rate of concordance(24%)than dizygotic twins(1-3%) The risk of a child developing lupus born from a mother (or father) with lupus is calculated to be 3-4%at worst

Epidemiology • Incidence: 1 in 1,000 -10,000 • Female to male ratio: 9-1 • More common in African-Americans but it affects all races • Mean age of onset: 28 years • Positive family history in 10 -15% of patients • Monozygotic twins exhibit a greater rate of concordance (24%) than dizygotic twins (1-3%) • The risk of a child developing lupus born from a mother (or father) with lupus is calculated to be 3-4% at worst

Etiology The cause(s)of lupus is currently unknown, but there are environmental and genetic factors involved It seems likely that most of the genes predisposing to SLE are normal An individual inherits an unlucky combination of normal genetic polymorphisms, each of which permit a little immune overreponse or presentation of high quantities of target antigens in certain tissues. The combination of which is just enough to permit SLE to evolve after some environmental stimulus

Etiology • The cause(s) of lupus is currently unknown, but there are environmental and genetic factors involved.  It seems likely that most of the genes predisposing to SLE are normal.  An individual inherits an unlucky combination of normal genetic polymorphisms, each of which permit a little immune overreponse, or presentation of high quantities of target antigens in certain tissues. The combination of which is just enough to permit SLE to evolve after some environmental stimulus

Immunogenetics Increased Risk for SLE in: HLA-DR2 (anti-DNA Abs) HLA-DR3(anti-Ro Abs) Null alleles at c2 and C4 loci SLE may be transmitted in an autosomal dominant pattern(family studies)

Immunogenetics Increased Risk for SLE in: • HLA-DR2 (anti-DNA Abs) • HLA-DR3 (anti-Ro Abs) • Null alleles at C2 and C4 loci • SLE may be transmitted in an autosomal dominant pattern (family studies)

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, beta￾blokers, 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