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21-11-第十一节 小 结
自身抗体是特异性疾病过程的早期重要标志。有的自身抗体是通过与靶抗原结合的方式引发疾病;有的则是通过形成免疫复合物间接地启动免疫损伤;也有的抗体虽然不表现为直接或间接的致病性，但对系统性自身免疫病的部分亚型仍具有高度特异性。最后一类自身抗体在诸如狼疮、硬皮病、多发性肌炎和干燥综合征等系统性自身免疫病的血清学诊断中得到广泛应用。研究抗核抗体产生的机制是一个非常有意义和非常活跃的研究领域。通过干预自身抗体产生以起到治疗作用已在小鼠模型上得到初步证实，目前该方法还处于临床试验阶段。 8 ~% A$ F# \3 a% Q5 {/ N
(Westley H. Reeves, Sonali Narain, JingSong Wang)
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参考文献：
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Physical association of two nuclearantigens and mutual occurrence of their antibodies: the relation-ship of the Sm and RNA protein (Mo) systems in SLE sera. JImmunol, 1973. 110:1318一1324 McCarty DJ, Manzi S, Medsger TAJ, Ramsey-Goldman R,LaPorte RE, Kwoh CK. Incidence of systemic lupus erythemato-sus: race and gender differences. Arthritis Rheum, 1995. 38:1260一1270 McCauliffe DP, Wang L, Satoh M, Reeves WH, Small D.Recombinant 52 kD Ro (SSA) ELISA detects autoantibodies inSjogren's syndrome sera that go undetected by conventional sero-logic assays. J Rheumatol, 1997. 24:860一866 McCauliffe DP, Yin H, Wang LX, Lucas L. Autoimmunesera react with multiple epitopes on recombinant 52 and 60 kD Ro(SSA) proteins. J Rheumatol, 1994. 21:1073一1080 McCauliffe DP. Cutaneous diseases in adults associated withanti-Ro/SS-A autoantibody production. Lupus, 1997. 6:158一166 McCauliffe DP. Neonatal lupus erythematosus: a transpla-centally acquired autoimmune disorder. Semin Dermatol, 1995.14:47一53 McNeilage LJ, Youngchaiyud U, Whittingham S. Racialdifferences in antinuclear antibody patterns and clinical manifesta-tions of scleroderma. Arthritis Rheum, 1989. 32:54一60 Medsger TA. Systemic sclerosis(scleroderma )，localizedforms of scleroderma, and calcinosis. In: McCarty DJ, KoopmanWJ，editors. Arthritis and Allied Conditions. Philadelphia: Lea&Febiger, 1993: 1253一1292 Metcalf JV, Mitchison HC, Palmer JM, Jones DE,Bassendine MF, James OFW. Natural history of early primarybiliary cirrhosis. Lancet, 1996. 348:1399一1402 Miller FW, Twitty SA, Biswas T, Plotz PH. Origin andregulation of a disease-specific autoantibody response. Antigenicepitopes, spectrotype stability, and isotype restriction of anti-Jo-1autoantibodies. J Clin Invest, 1990. 85:468一475 Miller FW, Waite KA, Biswas T, Plotz PH. The role of anautoantigen, histidyl-tRNA synthetase, in the induction andmaintenance of autoimmunity. Proc Natl Acad Sci USA, 1990.87:9933一9937 Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S,Homma M. Characterization of a high molecular weight acidic nu-clear protein recognized by autoantibodies from patients withpolymyositis-scleroderma overlap. J Clin Invest, 1981. 68:611一620 Mimori T, Hardin JA, Steitz JA. Characterization of theDNA-binding protein antigen Ku recognized by autoantibodiesfrom patients with rheumatic disorders. J Biol Chem, 1986.261:2274一2278 Miranda-Carus ME, Askanase AD, Clancy RM, di DonatoF, Chou TM, Libera MR et al. Anti-SSA/Ro and anti-SSB/Laautoantibodies bind the surface of apoptotic fetal cardiocytes andpromote secretion of TNF-alpha by macrophages. J Immunol,2000. 165(9) :5345一5351 Mitchison HC, Lucey MR, Kelly巧，Neuberger JM,Williams R, James OFW. Symptom development and prognosisin primary biliary cirrhosis: a study in two centers. Gastroen-terology, 1990. 99:778一784 Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nucle-ar antigen in proliferating cells. J Immunol, 1978. 121:2228一2234 Miyachi K, Tan EM. Antibodies reacting with ribosomal ri-bonucleoprotein in connective tissue diseases. Arthritis Rheum,upus erythematosus. Proc Natl Acad Sci USA, 1979. 76:5495一5499 Li JM, Horsfall AC, Maini RN. Anti-La(SS-B) but not an-ti-Ro52 (SS-A) antibodies cross-react with laminin- a role inthe pathogenesis of congenital heart block? Clin Exp Immunol,1995. 99:316一324 Litsey SE, Noonan JA, O’Connor WN, Cottrill CM,Mitchell B. Maternal connective tissue disease and congenitalheart block. N Engl J Med, 1985. 312:98一100 Locker JD, Medof ME, Bennett RM, Sukhupunyaraksa S.Characterization of DNA used to assay sera for anti-DNA antibod-ies; determination of the specificities of anti-DNA antibodies inSLE and non-SLE rheumatic disease states. J Immunol, 1977.118:694一701 Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M,Plotz PH et al. A new approach to the classification of idiopathicinflammatory myopathy: myositis-specific autoantibodies define auseful homogeneous patient group. Medicine, 1991.70:360一374 Masi AT, Rodnan GP, Medsger TA, Altman RD, D' An-gelo WA, Fries JF. Subcommittee for Scleroderma Criteria of theAmerican Rheumatism Association Diagnostic and TherapeuticCriteria Committee: Preliminary criteria for the classification ofsystemic sclerosis (scleroderma).Arthritis Rheum, 1980. 23:581一590 Maskarinec G, Katz AR. Prevalence of systemic lupus ery-thematosus in Hawaii: is there a difference between ethnicgroups? Hawaii Med J, 1995. 54(2) :406一409 Mattioli M, Reichlin M. Heterogeneity of RNA proteinantigens reactive with sera of patients with systemic lupus erythe-matosus: description of a cytoplasmic nonribosomal antigen.Arthritis Rheum, 1974. 17:421一429 Mattioli M, Reichlin M. Physical association of two nuclearantigens and mutual occurrence of their antibodies: the relation-ship of the Sm and RNA protein (Mo) systems in SLE sera. JImmunol, 1973. 110:1318一1324 McCarty DJ, Manzi S, Medsger TAJ, Ramsey-Goldman R,LaPorte RE, Kwoh CK. Incidence of systemic lupus erythemato-sus: race and gender differences. Arthritis Rheum, 1995. 38:1260一1270 McCauliffe DP, Wang L, Satoh M, Reeves WH, Small D.Recombinant 52 kD Ro (SSA) ELISA detects autoantibodies inSjogren's syndrome sera that go undetected by conventional sero-logic assays. J Rheumatol, 1997. 24:860一866 McCauliffe DP, Yin H, Wang LX, Lucas L. Autoimmunesera react with multiple epitopes on recombinant 52 and 60 kD Ro(SSA) proteins. J Rheumatol, 1994. 21:1073一1080 McCauliffe DP. Cutaneous diseases in adults associated withanti-Ro/SS-A autoantibody production. Lupus, 1997. 6:158一166 McCauliffe DP. Neonatal lupus erythematosus: a transpla-centally acquired autoimmune disorder. Semin Dermatol, 1995.14:47一53 McNeilage LJ, Youngchaiyud U, Whittingham S. Racialdifferences in antinuclear antibody patterns and clinical manifesta-tions of scleroderma. Arthritis Rheum, 1989. 32:54一60 Medsger TA. Systemic sclerosis(scleroderma )，localizedforms of scleroderma, and calcinosis. In: McCarty DJ, KoopmanWJ，editors. Arthritis and Allied Conditions. Philadelphia: Lea&Febiger, 1993: 1253一1292 Metcalf JV, Mitchison HC, Palmer JM, Jones DE,Bassendine MF, James OFW. Natural history of early primarybiliary cirrhosis. Lancet, 1996. 348:1399一1402 Miller FW, Twitty SA, Biswas T, Plotz PH. Origin andregulation of a disease-specific autoantibody response. Antigenicepitopes, spectrotype stability, and isotype restriction of anti-Jo-1autoantibodies. J Clin Invest, 1990. 85:468一475 Miller FW, Waite KA, Biswas T, Plotz PH. The role of anautoantigen, histidyl-tRNA synthetase, in the induction andmaintenance of autoimmunity. Proc Natl Acad Sci USA, 1990.87:9933一9937 Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S,Homma M. Characterization of a high molecular weight acidic nu-clear protein recognized by autoantibodies from patients withpolymyositis-scleroderma overlap. J Clin Invest, 1981. 68:611一620 Mimori T, Hardin JA, Steitz JA. Characterization of theDNA-binding protein antigen Ku recognized by autoantibodiesfrom patients with rheumatic disorders. J Biol Chem, 1986.261:2274一2278 Miranda-Carus ME, Askanase AD, Clancy RM, di DonatoF, Chou TM, Libera MR et al. Anti-SSA/Ro and anti-SSB/Laautoantibodies bind the surface of apoptotic fetal cardiocytes andpromote secretion of TNF-alpha by macrophages. J Immunol,2000. 165(9) :5345一5351 Mitchison HC, Lucey MR, Kelly巧，Neuberger JM,Williams R, James OFW. Symptom development and prognosisin primary biliary cirrhosis: a study in two centers. Gastroen-terology, 1990. 99:778一784 Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nucle-ar antigen in proliferating cells. J Immunol, 1978. 121:2228一2ctive with retroviral p30gag antigen. Cell, 1987. 51:211一220 Raz E, Brezis M, Rosenmann E, Eilat D. Anti-DNA anti-bodies bind directly to renal antigens and induce kidney dysfunc-tion in the isolated perfused rat kidney. J Immunol, 1989. 142:3076一3082 Reeves WH, Chaudhary N, Salerno A, Blobel G. Lamin Bautoantibodies in sera of certain patients with systemic lupus ery-thematosus. J Exp Med, 1987. 165:750一762 Reeves WH, Fisher DE, Lahita RG, Kunkel HG. Autoim-mune sera reactive with Sm antigen contain high levels of RNP-like antibodies. J Clin Invest, 1985. 75:580一587 Reeves WH, Nigam SK，Blobel G. Human autoantibodiesreactive with the signal recognition particle. Proc Natl Acad SciUSA, 1986. 83:9507一9511 Reeves WH, Satoh M, McCauliffe DP. Autoantibody test-ing by non-FITC methods. In: Rose NR, Hamilton RG, DetrickB, editors. Manual of Clinical Laboratory Immunology. Washington, DC二American Society of Microbiology Press, 2002: 933一950 Reeves WH, Satoh M. Autoantibodies in systemic lupuserythematosus. In: Koopman WJ, editor. Arthritis and AlliedConditions. A Textbook of Rheumatology. Philadelphia: Lippin-cott Williams&Wilkins, 2001:1480一1502 Reeves WH, Wang J, Ajmani AK, Stojanov L, Satoh M.The Ku Autoantigen. In: Zanetti M, Capra JD, editors. TheAntibodies. Amsterdam: Harwood Academic Publishers, 1997:33一84 Reeves WH. Use of monoclonal antibodies for the character-ization of novel DNA-binding proteins recognized by human au-toimmune sera. J Exp Med, 1985. 161:18一39 Reichlin M, Brucato A, Frank MB, Maddison PJ, McCub-bin VR, Wolfson-Reichlin M et al. Concentration of autoantibod-ies to native 60-kd Ro/SS-A and denatured 52-kd Ro/SS-A ineluates from the heart of a child who died with congenital com-plete heart block. Arthritis Rheum, 1994. 3700:1698一1703 Reimer G, Rose KM, Scheer U, Tan EM. Autoantibody toRNA polymerase I in scleroderma sera. J Clin Invest, 1987. 79:65一72 Reimer G, Steen VD, Penning CA, Medsger TA, TanEM. Correlates between autoantibodies to nucleolar antigens andclinical features in patients with systemic sclerosis (scleroderma).Arthritis Rheum, 1988. 31:525一532 Reveille JD, Durban E, Goldstein R, Moreda R, ArnettFC. Racial differences in the frequencies of scleroderma-relatedautoantibodies. Arthritis Rheum, 1992. 35:216一218 RinkeJ, Steitz JA. Precursor molecules of both human 5Sribosomal RNA and transfer RNAs are bound by a cellular proteinreactive with anti-La lupus antibodies. Cell, 1982. 29:149一159 Robinson CP, Brayer J, Yamachika S, Esch TR, Peck AB,Stewart CA et al. Transfer of human serum IgG to nonobese dia-betic Igmu null mice reveals a role for autoantibodies in the loss ofsecretory function of exocrine tissues in Sjogren 's syndrome. ProcNatl Acad Sci USA, 1998. 95(13):7538一7543 Rosenberg AM, Semchuk KM, McDuffie HH, LedinghamDL, Cordeiro DM, Cessna习 et al. Prevalence of antinuclear an-tibodies in a rural population. J Toxicol Environ Health A, 1999.57(4):225一236 Rothfield NF, Stollar BD. The relation of immunoglobulinclass, pattern of anti-nuclear antibody, and complement-fixingantibodies to DNA in sera from patients with systemic lupus ery-thematosus. J Clin Invest, 1967. 46:1785一1794 Rothfield NF. Autoantibodies in scleroderma. Rheum DisClin North Am, 1992. 18:483一498 Rothfield NF. Autoantibodies to scleroderma-associated anti-gens. Invan Venrooij WJ, Maini RN, editors. Manual of Bio-logical Markers of Disease. Dordrecht Kluwer Academic Pub-lishers, 1996: 1一7 Rozman B, Boric B, Kos-Golja M, Plesivcnik-Novljan M,Kveder T. Immunoserological aspects of idiopathic inflammatorymuscle disease. Wien Klin Wochenschr, 2000. 112 (15一16):722一727 Rubin RL, Burlingame RW, Arnott JE, Totoritis MC, Mc-Nally EM, Johnson AD. IgG but not other classes of anti-[ (H2A-H2B)-DNA] is an early sign of procainamide-induced lu-pus. J Immunol, 1995. 154:2483一2493 Rubin RL. Hsstone (1-12A-H2B)-DNA autoantibodies. In Peter JB, Shoenfeld Y, editors. Autoantibodies. Amsterdam:Elsevier Science, 1996: 364一372 Rumore PM, Steinman CR. Endogenous circulating DNA insystemic lupus erythematosus: occurrence as multimeric complex-es bound to histone. J Clin Invest, 1990. 86:69一74 Sabbaga J, Line SRP, Potocnjak P, Madaio MP. A murinenephritogenic monoclonal anti-DNA autoantibody binds directly tomouse laminin, the major non-collagenous protein component ofthe glomerular basement membrane. Eur J Immunol, 1989. 19:137一143 Salmon JE, Millard S, Schachter LA, Arnett FC GinzlerEM, Gourley MF et al. Fc gamma RIIA alleles are heritable riskfactors for lupus nephritis in African Americans. J Clin Invest,1996. 97:1348一1354 Satoh M, Ajmani AK, Ogasawara T, Langdon JJ, HirakataM, Wang J et al. Autoantibodies to RNA polymerase II are com-mon in systemic lupus erythematosus and overlap syndrome. Spe-cific recognition of the phosphorylated (110) form by a subset of234 Miyachi K, Tan EM. Antibodies reacting with ribosomal ri-bonucleoprotein in connective tissue diseases. Arthritis Rheum,ctive with retroviral p30gag antigen. Cell, 1987. 51:211一220 Raz E, Brezis M, Rosenmann E, Eilat D. Anti-DNA anti-bodies bind directly to renal antigens and induce kidney dysfunc-tion in the isolated perfused rat kidney. J Immunol, 1989. 142:3076一3082 Reeves WH, Chaudhary N, Salerno A, Blobel G. Lamin Bautoantibodies in sera of certain patients with systemic lupus ery-thematosus. J Exp Med, 1987. 165:750一762 Reeves WH, Fisher DE, Lahita RG, Kunkel HG. Autoim-mune sera reactive with Sm antigen contain high levels of RNP-like antibodies. J Clin Invest, 1985. 75:580一587 Reeves WH, Nigam SK，Blobel G. Human autoantibodiesreactive with the signal recognition particle. Proc Natl Acad SciUSA, 1986. 83:9507一9511 Reeves WH, Satoh M, McCauliffe DP. Autoantibody test-ing by non-FITC methods. In: Rose NR, Hamilton RG, DetrickB, editors. Manual of Clinical Laboratory Immunology. Washington, DC二American Society of Microbiology Press, 2002: 933一950 Reeves WH, Satoh M. Autoantibodies in systemic lupuserythematosus. In: Koopman WJ, editor. Arthritis and AlliedConditions. A Textbook of Rheumatology. Philadelphia: Lippin-cott Williams&Wilkins, 2001:1480一1502 Reeves WH, Wang J, Ajmani AK, Stojanov L, Satoh M.The Ku Autoantigen. In: Zanetti M, Capra JD, editors. TheAntibodies. Amsterdam: Harwood Academic Publishers, 1997:33一84 Reeves WH. Use of monoclonal antibodies for the character-ization of novel DNA-binding proteins recognized by human au-toimmune sera. J Exp Med, 1985. 161:18一39 Reichlin M, Brucato A, Frank MB, Maddison PJ, McCub-bin VR, Wolfson-Reichlin M et al. Concentration of autoantibod-ies to native 60-kd Ro/SS-A and denatured 52-kd Ro/SS-A ineluates from the heart of a child who died with congenital com-plete heart block. Arthritis Rheum, 1994. 3700:1698一1703 Reimer G, Rose KM, Scheer U, Tan EM. Autoantibody toRNA polymerase I in scleroderma sera. J Clin Invest, 1987. 79:65一72 Reimer G, Steen VD, Penning CA, Medsger TA, TanEM. Correlates between autoantibodies to nucleolar antigens andclinical features in patients with systemic sclerosis (scleroderma).Arthritis Rheum, 1988. 31:525一532 Reveille JD, Durban E, Goldstein R, Moreda R, ArnettFC. Racial differences in the frequencies of scleroderma-relatedautoantibodies. Arthritis Rheum, 1992. 35:216一218 RinkeJ, Steitz JA. Precursor molecules of both human 5Sribosomal RNA and transfer RNAs are bound by a cellular proteinreactive with anti-La lupus antibodies. Cell, 1982. 29:149一159 Robinson CP, Brayer J, Yamachika S, Esch TR, Peck AB,Stewart CA et al. Transfer of human serum IgG to nonobese dia-betic Igmu null mice reveals a role for autoantibodies in the loss ofsecretory function of exocrine tissues in Sjogren 's syndrome. ProcNatl Acad Sci USA, 1998. 95(13):7538一7543 Rosenberg AM, Semchuk KM, McDuffie HH, LedinghamDL, Cordeiro DM, Cessna习 et al. Prevalence of antinuclear an-tibodies in a rural population. J Toxicol Environ Health A, 1999.57(4):225一236 Rothfield NF, Stollar BD. The relation of immunoglobulinclass, pattern of anti-nuclear antibody, and complement-fixingantibodies to DNA in sera from patients with systemic lupus ery-thematosus. J Clin Invest, 1967. 46:1785一1794 Rothfield NF. Autoantibodies in scleroderma. Rheum DisClin North Am, 1992. 18:483一498 Rothfield NF. Autoantibodies to scleroderma-associated anti-gens. In: van Venrooij WJ, Maini RN, editors. Manual of Bio-logical Markers of Disease. Dordrecht: Kluwer Academic Pub-lishers, 1996: 1一7 Rozman B, Boric B, Kos-Golja M, Plesivcnik-Novljan M,Kveder T. Immunoserological aspects of idiopathic inflammatorymuscle disease. Wien Klin Wochenschr, 2000. 112 (15一16):722一727 Rubin RL, Burlingame RW, Arnott JE, Totoritis MC, Mc-Nally EM, Johnson AD. IgG but not other classes of anti-[ (H2A-H2B)-DNA] is an early sign of procainamide-induced lu-pus. J Immunol, 1995. 154:2483一2493 Rubin RL. Hsstone (1-12A-H2B)-DNA autoantibodies. Ineter JB, Shoenfeld Y, editors. Autoantibodies. Amsterdam:Elsevier Science, 1996: 364一372 Rumore PM, Steinman CR. Endogenous circulating DNA insystemic lupus erythematosus: occurrence as multimeric complex-es bound to histone. J Clin Invest, 1990. 86:69一74 Sabbaga J, Line SRP, Potocnjak P, Madaio MP. A murinenephritogenic monoclonal anti-DNA autoantibody binds directly tomouse laminin, the major non-collagenous protein component ofthe glomerular basement membrane. Eur J Immunol, 1989. 19:137一143 Salmon JE, Millard S, Schachter LA, Arnett FC GinzlerEM, Gourley MF et al. Fc gamma RIIA alleles are heritable riskfactors for lupus nephritis in African Americans. J Clin Invest,1996. 97:1348一1354 Satoh M, Ajmani AK, Ogasawara T, Langdon JJ, HirakataM, Wang J et al. 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