Anti-carbonic anhydrase antibody in collagen diseases and its clinical significance

八年前，我们在胶原病患者的血清中偶然发现了一种新的自身抗体--抗碳酸氢酶抗体。从那时起，抗体的分析和频率，抗原性质的分析在我们组和其他组-在世界上也一直在不断地探索。应用酶联免疫吸附试验(EL ISA)方法，对109例日本胶原病患者进行血清抗CA-Il抗体筛查。在24.1%的SLE、16.7%的PSS、20.0%的干燥综合征和25.0%的皮肌炎患者血清中检测到CA-I和CA-II的抗原表位。我们制备了CA-I的P-1~P-21和CA-II的P-1~P-20的多肽抗原。利用这些多肽，应用酶联免疫吸附试验方法，从胶原病患者血清中筛选抗体。结果：抗P-1和P-2的CA-I抗体在SLE中呈阳性，在PSS中呈阳性，在干燥综合征中呈阳性，P-4呈阳性。此外，使用CA-Il的多肽还检测到SLE中的P-2和8，PSS中的P-8和15，干燥综合征中的P-2和8，皮肌炎中的P-8。抗P-20抗体是胶原病患者和健康志愿者血清中常见的表位，在2例SLE患者中，多年来观察到表位的扩散。下一步是找出并分析这些疾病中的一些致病表位。

Eight years ago, we discovered a novel autoantibody ; anti-carbonic anhydrase (CA) antibody in sera from patients with collagen diseases as a serendipitous finding. Since then, the analysis and frequency of antibody, the analyses of antigen natures have been continuously explored in our group and also in other groups -in the world. Using the ELISA method, we screened the serum anti CA-Il antibody in 109 Japanese collagen disease patients. The positive results were obtained in 24.1% of SLE sera, 16.7% of PSS, 20.0% of Sjogren's syndrome and 25.0% of dermatomyositis.To explore the epitope-peptides of CA-I and II, the epitope-mapping was performed. We prepared peptide-antigens from P-1 to P-21 of CA-I, and from P-1 to P-20 of CA-II. Using these peptides, antibody was screened in sera from collagen diseases, applying the ELISA method. As results, the specific antibodies of CA-I were presented against P-1 and 2 in SLE, against P-1 in PSS, and against P-4 in Sjogren's syndrome. Furthremore, antibodies were detected against P-2 and 8 in SLE, P-8 and 15 in PSS, P-2 and 8 in Sjogrens syndrome, and P-8 in dermatomyositis using peptides from CA-Il. The antibody against P-20 was common epitope among sera from the collagen diseases and healthy volunteers.In two cases of SLE, the epitope-spreading was observed in the course of several years. The next step is to find out and analyze some pathogenic epitopes in these diseases.