(Rheumatoid arthritis, RA)

2003 年春季学期 主讲：毕黎琦

内科学（风湿病）

(系统性红斑狼疮, SLE)

2005 spring Teacher：毕黎琦

( Rheumatology )

Section 3

Systemic Lupus Erythematosus(SLE)

Requirements: (教学要求)1.To know (了解) the etiology and pathology

of SLE.

2.To understand(理解) the pathogenesis of SLE.

3.To grasp (掌握) the clinical manifestation,

diagnosis, laboratory examination of SLE .

4.To be familial (熟悉) with the treatment and

differential diagnosis of SLE.

Introduction

Definition ： SLE is a typical autoimmune disease, in which many systems are involved, its character is many autoantibodies in patients’s serum.

SLE is an autoimmune disease, many systems are involved, many autoantibodies in patients’ serum. 系统性红斑狼疮是一种典型的自身免疫病，多个系统受累和血清中出现多种自身抗体是其特征。

Epidemiology:

> 90% cases are women(in child bearing age)

men :women = 1:7~9 Prevalence:in China ： 70 per 100,000 population in Whites:25.7 per 100,000 population in Blacks:75.4 per 100,000 population

most of the cases are women in child-bearing age.

Etiology and pathogenesis ( 病因和发病机理 )

The exact etiology is unknown.

1. Genetic factor ( 遗传因素 )

(1) Race differences ： more common in blacks than in

whites.

(2) family gathering: 5 –13% of SLE patients have an

affected first- or second- degree relative).

(3) Twins concordance rate ： monozygotic twins( 同卵孪 生 ):50% ； dizygotic twins ( 异卵孪生 ):2-9%.

(4) MHC HLA HLA-I: A,B,C loci(locus) HLA-II:DP,DQ,DR loci HLA-III: complement C2,C4,B factor,TNF-α,β

HLA-DR,DQ and HLA-C2,C4 closely associated with autoantibodies production that define clinical manifestation. HLA-DRB1------anti ds-DNA------lupus nephritis

HLA-DQW6------anti-Sm production

lupus anticoagulant ------clotting

HLA autoantibodies different clinical manifestations different clinical subsets.

SLE is a heterogeneous diseases.

2. Environmental factor

(1) ultraviolet light （紫外线） : 40% SLE photosensitive

ultraviolet B may cause flares of SLE (DNA antigenicity,

cytokines production)

Photosensitivity by ultraviolet with wave length of 290-320nm.

(2) drugs: induce lupus like syndroms called “drug-induced

lupus” ( 药物性狼疮 ) 。

notable clinical and autoantibody differences between drug-

induced lupus and spontaneous lupus.

Drugs: hydralazine( 肼苯哒嗪 ),D-penicillamine( 青霉胺 ),

procainamide( 普鲁卡因酰胺 ),Rimifon( 雷米封 ),etc.

(3) hypersensitivity( 过敏 )

hypersensitivity may aggravate and recur the

diseases(SLE).

(4) infection:

Pathogenic micro-organisms stimulating factor

induce SLE .

infectious agent (superantigen 超抗原 , and lipopoly-

saccharides, 脂多糖 ) can activate monocytes, B cells, T

cells. worsen SLE.

SLE children more likely to have evidence of EBV

infection than normal subjects..

3.Sexual hormone femaleness a susceptable factor during reproductive years in human SLE, female to male ratio: is 9:1 between menarche( 月经初潮 ) and menopause( 绝经期 ),

is 3:1 in young (pre-menarche)and old (post-menopause) metabolism of estrogen( 雌激素 ) and androgen （雄 激素） abnormal. Men and women with SLE have too much estrogen and too little androgen, influence immune tolerance. prolactin( 泌乳素 )levels are elevated in some SLE ,increase disease activity

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4. Immune abnormality

Imbalance of cellular and humoral immunity A.T lymphocyte abnormality Immunoregulatory T cells, 2 types: (1) helper T cell( 辅助 )(Th, CD4 ＋ ), help B cell antibody (2) suppressor T cell( 抑制 )(Ts, CD8 ＋ ) inhibit B antibo

dy in SLE: Th :increased number, in hyper-functional state Ts :decreased number, in hypo-functional state production of cytokines are increased: IL-1,IL-2, IL-4,

IL-6,sIL-2R. IL-6 associated with CNS SLE.

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4. Immune abnormality B. hyperfunction （功能亢进） of B lymphocyte: B cell highly activated(T regulate, activator) pro

duce many kinds of autoantibodies ------major characteristics of SLE in immunology.

C.The formation and deposition of circulating immune complexes(CIC ，循环免疫复合物 ) in tissue may play an important role in the pathogenesis of SLE.

Target tissue damage is caused by pathogenic autoantibodies, immune complexes, and T lymphocytes.

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