自体免疫疾病(课件).ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,.,*,自体免疫疾病,器官特异性,非器官特异性,自体免疫疾病,肌肉,肾脏,皮肤,关节,Pathological Factors in Rheumatic Disorders,Rheumatic diseases are multisystem disorders caused by tissue damage resulting from autoantibodies,cytotoxic T lymphocytes,complement-fixing immune complex deposition,and inflammatory mediators,Inflammatory Parameters,ESR,Acute phase reactants,Immunoglobulins,Complement components,Inflammatory mediators:cytokines,prostanoids,ESR are determined by the three forces,Surface free energy(Van de Waal,s force):cohesive force,Electrical charge associated with RBC:repulsive force,Dielectric constant of the medium:dissipates the force,Calculation Equation for ESR,Vs=2/9x(Ps-PL)R2/n x g,Vs=the limiting velocity of the sphere,R=the radius of the sphere,Ps and PL=the densities of the sphere and of the liquid,g=the acceleration due to gravity,n=the viscosity of the liquid,Serum Proteins and Drugs That Affect the ESR Rate,ESR increase,ESR decrease,Fibrinogen,ACTH,Immunoglobulins,Cortisone,Dextran,Ethambutol,Methyldopa,Quinine,Procainamide,Salicylate,Oral contraceptives,Penicillamine,Methylsergide,Theophylline,Trifluperidol,Vitamine A,Acute Phase Reactants,The Acute Phase Response Follows Cell Injury and Tissue Damage Caused by:,Acute infections:i.e.,bacterial or parasitic,Trauma:i.e.,blunt,surgery,and burns,Ischemic necrosis:i.e.,acute myocardial infarction,Malignant disease:I.e.,tumor growth and metastasis,Connective tissue disease:i.e.,rheumatoid arthritis,rheumatic fever and others,Acute abdominal inflammation:i.e.cholecystitis and pancreatitis,Vaccination:I.e.,typhoid,Functional Properties of Human Acute Phase Proteins,Functional Group,Protein,Function,Host defense proteins,C-reactive protein(CRP),Complement activation,opsonication,Mannan-binding protein(MBP),Complement activation,opsonization,Complement proteins,C3,C4,C5,Factor B,C9,Factor H,C4bp,Increased vascular permeability,opsonization,bacterial killing,Fibrinogen,Formation of hemostatic plugs,wound healing,Proteinase inhibitors,1-Proteinase inhibitor(1-PI),Control of extracellular matrix degradation,1-Antichymotrypsin(1-Achy),Control of extracellular matrix degradation,2-Antiplasmin(2-AP),Control of plasmin,C1 inhibitor(C1 INH),Control of complement and contace system activation,Antioxidants,Ceruloplaasmin,Inhibition of oxy radical formation,Hemopexin(Hx),Binding of heme,inhibition of lipid peroxidation,Haptoglobulin(HP),Binding of hemoglobulin,inhibition of lipid peroxidation,Function unknown,Serum amyloid A(SAA),1-Acid glycoprotein,C-Reactive Protein(CRP),Normal plasma protein,concentration from 0.068-8.8 mg/ml,Acute phase reactant,concentration up to 500mg/ml,Synthesized by hepatocytes,Molecular weight 105,500 daltons,Five identical non-glycosylated,non-covalently associated subunits,Amino acid sequence homologous with serum amyloid A component(SAA),Rheumatic Disease in Which Elevated C-Reactive Protein Levels may Occur,Gout,Rheumatoid arthritis,Juvenile rheumatoid arthritis,Psoriatic arthritis,Ankylosing spondylitis,Reiter,s syndrome,Polymyalgia rheumatica-giant cell arteritis,Systemic vasculitis,Wegener,s granulomatosis,Behcet,s syndrome,Systemic lupus erythematosus,c ACR,类风湿性关节炎,(RA),类风湿性关节炎,(RA),类风湿性关节炎是一种重要的自体免疫疾病，可导致关节破坏变形，骨骼变化以及全身性的病变。,类风湿性关节炎的骨骼变化包括发炎关节旁的骨缺乏，软骨侵蚀。,类风湿性关节炎是一种全身性的变化，患者不但关节疼痛，可能关节会逐渐变形。,过去十年来，类风湿关节炎在冶疗上的改变有着明显的进步。我们不再视其为一仅局限于关节的慢性病变；反之，却视为一甚富侵略性的全身性疾患。,Rheumatoid Arthritis(RA),A chronic,systemic,autoimmune,inflammatory disease of unknown etiology,Characterized by,persistent intense immunological activity,inflammatory and erosive synovitis,usually involving peripheral joint in a symmetric fashion,local destruction of bone and cartilage,a variety of systemic manifestation.,The most common inflammatory joint disease,Normal Synovium,Rheumatoid Synovium,c ACR,c Arthritis&Rheumatism Foundation,Page No.20/52,Clinical features of Rheumatoid Arthritis in the hand,Early,Wasting small muscles,Extensor tendon sheath swelling,Fusiform swelling of PIP joints,MCP joint synovitis with swelling,Late,Deformity,Ulnar deviation,Swan-neck deformity,Subluxation of MCPJ,2.Loss of function,类风湿性关节炎,(RA),Rheumatoid arthritis,类风湿性关节炎,(RA),类风湿性关节炎,(RA),类风湿关节炎的早期关节破坏,类风湿性关节炎的临床病程,变异性极大,只有小于,1/5,的病人在发病,10-12,年内没有出现关节破坏或变形,在发病头六年内关节破坏进展最快,(1st2nd3rd.),在发病头两年内对于关节功能的影响最显着,Markers of severe disease activity in RA,1.General polyarthritis involving both small and large joints,2.Extra-articular disease,especially nodules and vasculitis,3.Persistently elevated ESR or CRP with active synovitis,4.RF-positive with high titier,5.Radiologically erosions within two years of disease onset,6.HLA-DR4 positive,Major extra-articular features of RA,Common,Anemia,Lymphadenopathy,Rheumatoid nodules,Muscle wasting,Episcleritis and keratoconjuntivitis,Peripheral sensory polyneuropathy,Uncommon,Pleural effusion,Pulmonary fibrosis,Pericardial effusion,Systemic vasculitis,Splenomegaly,Rheumatoid Factors,An autoantibody reactive with denatured human or rabbit IgG,Generation of RFs in the following conditions:,Autoimmune disorders:RA,SLE,Sjogren,s syndrome,vasculitis,Chronic inflammation,Chronic infection,Malignancy,aging,Some Disease Commonly Associated with Rheumatoid Factor,Rheumatic Diseases,Filariasis,Rheumatoid arthritis,Chronic Bacterial infections,Systemic lupus erythematosus,Tuberculosis,Scleroderma,Leprosy,Mixed connective tissue disease,Yaws,Sjogren,s syndrome,Syphilis,Viral Infections,Brucellosis,Acquired immunodeficiency syndromes,Subacute bacterial endocarditis,Mononucleosis,salmonellosis,Hepatitis,Neoplasms,Influenza,Tumors after radiation therapy or chemotherapy,After vaccination(may yield falsely elevated,Other Hyperglobulinemic States,titers of antivival antibodies),Hypergammaglobulinemic purpura,Parasitic Infections,Cryoglobulinemia,Trypanosomiasis,Chronic liver disease,Kala-azar,Sarcoid,Malaria,Other chronic pulmonary diseases,Schistosomiasis,False Positive Rheumatoid Factor Test,Sarcoidosis 10%,Syphilis 10%,Hepatitis 25%,Viral infection 15%,Leprosy 25%,Subacute bacterial endocarditis 50%,Old age(65y/o)35%,Biomarkers in Rheumatoid Arthritis,Rheumatoid factor,Anti-CCP(anti-cyclic citrullinated peptides)Ab,The presence of anti-CCP Ab is the most accurate biomarker for RA in both selected and unselected cohorts,Goals of RA Management,Pain relief and inflammation reduction,Activities of daily living and quality of life,Longterm joint damage control or prevention,Disease process interruption or modification,Therapy related side effects avoidance,僵直性脊椎关节炎,(AS),全身红斑性狼疮,好发于,20-40,岁之年轻女性,女性与男性之比例约为,10:1,侵犯多个器官系统,临床表现千变万化难以捉摸,全身红斑性狼疮,全身红斑性狼疮,全身红斑性狼疮与自体抗体,患者体内常出现许多自体抗体,最常出现之自体抗体为抗核抗体,(ANA),自体抗体为造成导致器官伤害的重要原因,有些自体抗体为追踪病情之重要指针,Antinuclear Antibody(ANA)Disease,Disease,Patients with ANAs(%),Systemic lupus erythematosus,99,Drug-induced lupus,100,Systemic sclerosis,97,Mixed connective tissue disease,93,Polymyositis and dermatomyositis,78,Sjogren,s syndrome,96,Specific Autoantibodies,Organ specific autoantibodies,Autoantibodies for systemic autoimmune disoeders,Autoantibodies in systemic lupus erythematosus,器官特异性自体免疫疾病对应抗原的种类,疾 病,自 体 抗 原,桥本氏甲状腺炎,(Hashimoto,s thyroiditis),Thyroid peroxidase(microsomal antigen),Thyroglobulin,Thyroid-stimulating immunoglobulin,葛雷氏病,(Grave,s disease),Thyroid peroxidase,Thyroglobulin,Thyroid-stimulating immunoglobulin(TSI),Thyroid growth-stimulating ikmmunoglobulin(TGSI),Thyrotropinbinding-inhibitory immunoglobulin(TBII),第一型糖尿病,Insulin,insulin receptors,islet cells,胰岛素抗性糖尿病,Insulin,insulin receptors,爱迪生病,(Addison,s disease),Adrenal cortex,恶性贫血,(Pernicious anemia),Intrinsic factor,parietal cells,重症肌无力,Acetycholine receptors,多发性硬化症,(Multiple sclerosis),Myelin basic protein,Goodpasture,s,病,Basement membrane(lung and glomeruli),寻常性天疱疮,(pemphigus vulgaris),Intracellular cement,水泡性类天疱疮,(Bullous pemphigoid),Basement membrane(skin),非分节性白斑症,(Non-segmental vitiligo),Membrane proteins on keratinocyte and melanocyte,自体免疫抗体与全身性自体免疫疾病之相关,自体免疫抗体,相关之疾病,Anti-dsDNA,SLE,Anti-Sm,SLE,Anti-lamin,SLE,Anti-histone,SLE,Drug-induced lupus,Anti-U1 RNP,SLE,MCTD,Anti-SSA/Ro,SLE,Sjogren,s syndrome,Anti-SSB/La,SLE,Sjogren,s syndrome,Anti-PCNA/cyclin,SLE,Anti-ribosomal P,NP-SLE,Anti-Scl-70/topoisomerase I,Scleroderma,Anti-Ku,SLE,scleroderma,Anti-centromere/kinetochore,CREST,Anti-RNA polymerase I,Scleroderma,Anti-PM-Scl,Scleroderma,Anti-Jo-1(tRNA synthetase),Polymyositis,Anti-cardiolipin,Anti-phospholipid sydnrome,Anti-neutrophil cytoplasmic antigen,Wegener,s granulomatosis,other vasculitis,List of Autoantibodies Reported in SLE,Against:,1.ANA,17.PCNA/Cyclin,33.Ribosomal-P,47.Poly(ADP ribose),2.SsDNA,18.HTLV-1,34.Ca nephritic factor,48.Poly(A)polymerase,3.DsDNA,19.HIV-gp120,C3 convertaseC1q,49.Protein kinase N II,4.Z-DNA,20.Mycobacteria,35.Antiendothelial,50.Prothymosin,5.Poly I,21.Laminin,36.Fibronectin,51.Replication protein A,6.Poly G,22.Heat shock protein(90kD),37.Golgi apparatus,52.Sp 100,7.Poly(dt),23.Klebsiella,38.Mitotic spindle apparatus,53.RA-33,8.Histones,24.Vimentin,39.Mi/Ma/Mc,54.Nucleosomes,9.Cardiolipin,25.Heparan sulfate,40.Annexin XI,55.Ubiquitine,10.ENA,26.LAC/Fac II,VIII,XII),41.DNA polymerase,56.Glycosaminoglycans,11.RNP/hn RNP,27.Lymphocytes(LCTA,Ts,NK),-RNA polymerase I-III,57.Lipocortin-1,12.Sm,28.Erythrocytes(Coombs,),42.HMG-1,2,17,58.Pyruvate dehydrogenase,13.SS-A/Ro,29.Platelets,43.L7,59.Anti-P ribosomal protein,14.SS-B/La,30.Leukocytes,44.Nuclear helicase,15.RNA,31.Neuronal,45.Nucleosides,16.Ku/Ki(SL),32.Glycolipids,46.C-myc,全身红斑性狼疮,常见慢性并发症,1.,肾炎及肾脏衰竭,2.,中枢神经病变,3.,感染症,4.,贫血及血小板降低,全身红斑性狼疮的活动性与复发,活动性,(SLE activity),复发,(flare up),常见症状,:,发烧,关节炎,水肿加重,红斑,癫痫发作,呼吸困难,起伏不定,难以捉摸,影响全身红斑性狼疮复发的因素,阳光曝晒 紫外线,怀孕,压力与情绪,感染,全身红斑性狼疮活动性的追踪,1.,抗,DNA,抗体,2.,补体,C3,C4,3.,发炎指针,血球 及肾功能,免疫学检查与全身红斑性狼疮活动性,临床症状,临床前期之复发,Algorithm for the use of antinuclear antibodies(ANAs)in the diagnosis of connective tissue disorders,Anti-Neutrophil Cytoplasmic Antibodies(ANCA),cANCA:anti-proteinase 3(serine proteinase),pANCA:anti-myeloperoxidase(MPO),Disease-Association of ANCA,Disease entity Anti-PR3 Anti-MPO,(%)(%),Wegener,s granulomatosis 85 10,Microscopic polyangiitis 45 45,Idiopathic crescentic,glomerulonephritis 25 65,Churg-Strauss symdrome 10 60,Polyarteritis nodosum 5 15,