원발담즙간경변증 진단에서 항-MIT3, 항-gp210, 항-sp100 항체 검사의 성능 비교평가
A Comparative Evaluation of the Performances of Anti-MIT3, Anti-gp210, and Anti-sp100 Antibodies for the Diagnosis of Primary Biliary Cirrhosis
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배경: 원발담즙간경변증환자(PBC)들에서 항미토콘드리아항체(AMA)나 항핵항체(ANA) 등의 자가항체들이 검출되는데 이중 AMA 검사는 PBC의 중요한 진단표지자이다. AMA는 전통적으로 간접면역형광법(IF)을 이용하여 검출하는데 오류의 소지가 많다. 최근 AMA가 반응하는 특이항원을 이용한 효소면역검사법과 PBC에 특이적인 항핵항체 검사법이 개발되었다. 저자들은 PBC 환자에서 AMA 효소면역검사법 검출법의 하나인 항-MIT3 항체 검사와 PBC 특이 항핵항체인 항-sp100과 항-gp210 항체검사의 PBC에 대한 진단성능을 기존의 AMA IF 검사와 비교 평가하였다. 방법: PBC가 의심되어 AMA 검사가 의뢰된 환자, 다른 자가면역질환 환자 그리고 건강검진자를 포함하여 총 130예를 대상으로 하였으며 병록지 조회을 통하여 PBC 진단을 확인하였다. 총 130예의 혈청을 대상으로 AMA IF 검사와 항-MIT3 효소면역검사, 그리고 항-sp100과 항-gp210 효소면역검사를 시행하였다. PBC 진단에 대한 항-MIT3의 receiver-operating characteristics (ROC) 곡선분석을 통하여 area under the curve (AUC)와 판정기준치를 구했다. AMA IF에 비교하여 항-MIT3, 항-gp210과 항-sp100 항체의 PBC에 대한 진단성능을 비교하였다. 항-sp100 또는 항-gp210 항체의 유무와 PBC의 진단 및 생화학지표 이상과의 연관성을 조사하였다. 결과: 항-MIT3는 PBC 진단에 대한 ROC곡선에서 AUC는 0.934 (95% CI, 0.877-0.970)이었으며 AMA IF와 93.8%의 결과 일치도(κ, 0.82)를 보였다. 항-MIT3와 AMA IF 모두 민감도는 100%였고, 특이도는 각각 83.1% 그리고 81.4%였다. 항-gp210과 항-sp100의 민감도는 41.7%, 16.7%였고 특이도는 각각 94.9%, 97.5%였다. 항-sp100 항체와 달리 항-gp210 양성은 PBC 진단과 유의한 연관성이 있었으며(P=0.0001), PBC에 대한 양성예측도는 45.5%로 평가한 항체들 중 가장 높았다. 결론: 항-MIT3 검사는 기존의 AMA IF법과 견주어 동등한 진단성능을 가진다. 항-gp210 검사는 PBC 진단을 위해 AMA에 보완적인 유용성이 있을 것으로 생각된다.
Abstract
Background: Anti-mitochondrial antibody (AMA) is a serological hallmark of primary biliary cirrhosis (PBC). AMAs are detected by an immunofluorescence assay (IF), which is subject to errors. We evaluated the diagnostic performances of the AMA ELISA test (the anti-MIT3 antibody) and PBC-associated antinuclear antibody (ANA) tests (the anti-gp210 and anti-sp100 antibodies). Methods: AMA, anti-gp210, and anti-sp100 were measured in the sera of 130 subjects including patients for whom the AMA test was requested with the clinical suspicion of PBC, patients with other autoimmune diseases, and those undergoing health check-ups. AMA was detected by both IF and ELISA (anti-MIT3 antibodies), and anti-gp210 and anti-sp100 were detected by ELISA. The diagnostic performances of the anti-MIT3, anti-gp210, and anti-sp100 were compared with that of the AMA IF test. Associations between the presence of anti-sp100 or anti-gp210 and the diagnosis and biochemical abnormalities of PBC were investigated. Results: The area under the curve of anti-MIT3 for the diagnosis of PBC was 0.934 (95% confidence interval, 0.877-0.970), and the agreement between anti-MIT3 and AMA IF was 93.8% (κ, 0.82). The sensitivities of anti-MIT3 and AMA IF were both 100%, and the specificities were 83.1% and 81.4%, respectively, whereas the sensitivities of anti-gp210 and anti-sp100 were 41.7% and 16.7%, and their specificities were 94.9% and 97.5%, respectively. The presence of anti-gp210 was associated with the diagnosis of PBC (P=0.0001), but that of anti-sp100 was not. Conclusions: The diagnostic performance of anti-MIT3 is comparable to that of AMA IF. Anti-gp210 seems to be complementary to AMA for the diagnosis of PBC.
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