THE ANTIPERINUCLEAR FACTOR AND THE SO-CALLED ANTIKERATIN ANTIBODIES ARE THE SAME RHEUMATOID ARTHRITIS-SPECIFIC AUTOANTIBODIES

THE ANTIPERINUCLEAR FACTOR AND THE SO-CALLED ANTIKERATIN ANTIBODIES ARE THE SAME RHEUMATOID ARTHRITIS-SPECIFIC AUTOANTIBODIES
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DOI:
10.1172/jci117969
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发表时间:
1995-06-01
影响因子:
15.9
通讯作者:
SERRE, G
SERRE, G
中科院分区:
医学1区
文献类型:
--
作者:
SEBBAG, M;SIMON, M;SERRE, G

文献摘要

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抗角蛋白抗体(antikeratinantibodies,AKA)和抗核周因子(antiperinuclearfactor,APF)是类风湿关节炎最特异的血清学标志物。AKA标记各种上皮细胞的角质层,APF标记人颊粘膜上皮细胞的透明角质颗粒。我们报道了主要APF抗原的鉴定,其为200-400 kD的弥散蛋白带。该蛋白被认为与人表皮(原)聚丝蛋白密切相关,因为它被四种对不同表位特异的抗聚丝蛋白单克隆抗体识别,RA血清的APF滴度与AKA滴度和对丝聚蛋白的免疫印迹反应性相关。RA血清对纯化的表皮聚丝蛋白的免疫吸收消除了它们对颊上皮细胞颗粒和200-400 kD抗原的反应性。此外,抗聚丝蛋白自身抗体,即,从RA血清中亲和纯化的AKA可免疫检测200-400-kD的抗原,并可将这些颗粒染色,这些结果表明AKA和APF是基本相同的自身抗体。它们识别人表皮丝聚蛋白和颊上皮细胞丝聚蛋白相关蛋白,鉴定这些自身抗体识别的表位,我们建议将其命名为抗丝聚蛋白自身抗体,这必将为RA的病理生理学研究开辟新的途径。
The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA, Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium, We recently demonstrated that AKA recognize human epidermal filaggrin.Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD, This protein is seen to be closely related to human epidermal (pro)filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules.These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro)filaggrin-related proteins of buccal epithelial cells, Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.