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1、自体免疫疾病,许秉宁,台大医学院免疫学研究所台大医院内科部,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,
2、Inflammatory Parameters,ESRAcute phase reactantsImmunoglobulinsComplement componentsInflammatory mediators:cytokines,prostanoids,ESR are determined by the three forces,Surface free energy(Van de Waals force):cohesive forceElectrical charge associated with RBC:repulsive forceDielectric constant of th
3、e medium:dissipates the force,Calculation Equation for ESR,Vs=2/9x(Ps-PL)R2/n x gVs=the limiting velocity of the sphereR=the radius of the spherePs and PL=the densities of the sphere and of the liquidg=the acceleration due to gravityn=the viscosity of the liquid,Serum Proteins and Drugs That Affect
4、the ESR Rate,Acute Phase Reactants,The Acute Phase Response Follows Cell Injury and Tissue Damage Caused by:Acute infections:i.e.,bacterial or parasiticTrauma:i.e.,blunt,surgery,and burnsIschemic necrosis:i.e.,acute myocardial infarctionMalignant disease:I.e.,tumor growth and metastasisConnective ti
5、ssue disease:i.e.,rheumatoid arthritis,rheumatic fever and othersAcute abdominal inflammation:i.e.cholecystitis and pancreatitisVaccination:I.e.,typhoid,Functional Properties of Human Acute Phase Proteins,C-Reactive Protein(CRP),Normal plasma protein,concentration from 0.068-8.8 mg/mlAcute phase rea
6、ctant,concentration up to 500mg/mlSynthesized by hepatocytesMolecular weight 105,500 daltonsFive identical non-glycosylated,non-covalently associated subunitsAmino acid sequence homologous with serum amyloid A component(SAA),Rheumatic Disease in Which Elevated C-Reactive Protein Levels may Occur,c A
7、CR,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 etiologyChar
8、acterized by persistent intense immunological activityinflammatory and erosive synovitis,usually involving peripheral joint in a symmetric fashionlocal destruction of bone and cartilagea variety of systemic manifestation.The most common inflammatory joint disease,Normal Synovium,Rheumatoid Synovium,
9、c ACR,c Arthritis&Rheumatism Foundation,Page No.20/52,Clinical features of Rheumatoid Arthritis in the hand,Early,Wasting small musclesExtensor tendon sheath swellingFusiform swelling of PIP jointsMCP joint synovitis with swelling,Late,DeformityUlnar deviationSwan-neck deformitySubluxation of MCPJ,2
10、.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 joints2.Extra-arti
11、cular disease,especially nodules and vasculitis3.Persistently elevated ESR or CRP with active synovitis4.RF-positive with high titier5.Radiologically erosions within two years of disease onset6.HLA-DR4 positive,Major extra-articular features of RA,Common,AnemiaLymphadenopathyRheumatoid nodulesMuscle
12、 wastingEpiscleritis and keratoconjuntivitisPeripheral sensory polyneuropathy,Uncommon,Pleural effusionPulmonary fibrosisPericardial effusionSystemic vasculitisSplenomegaly,Rheumatoid Factors,An autoantibody reactive with denatured human or rabbit IgGGeneration of RFs in the following conditions:Aut
13、oimmune disorders:RA,SLE,Sjogrens syndrome,vasculitisChronic inflammationChronic infectionMalignancyaging,Some Disease Commonly Associated with Rheumatoid Factor,False Positive Rheumatoid Factor Test,Sarcoidosis 10%Syphilis 10%Hepatitis 25%Viral infection 15%Leprosy 25%Subacute bacterial endocarditi
14、s 50%Old age(65y/o)35%,Biomarkers in Rheumatoid Arthritis,Rheumatoid factorAnti-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 reductionActivities
15、of daily living and quality of lifeLongterm joint damage control or prevention Disease process interruption or modificationTherapy 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
16、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,Specific Autoantibodies,Organ specific autoantibodiesAutoantibodies for systemic autoimmune disoedersAutoantibodies in systemic lupus erythematosus,器官特异性自体免疫疾病对应抗原的种类,自体免疫抗体与全身性自体免疫疾病之相关,List of Autoantibodies Reported in SLE,全身红斑性狼疮,常见慢性
17、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
18、 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(%)(%)Wegeners granulomatosis 85 10Microscopic polyangiitis 45 45Idiopathic crescentic glomerulonephritis 25 65Churg-Strauss symdrome 10 60Polyarteritis nodosum 5 15,
