臺灣特發性發炎性肌病變病患之階層式分群特徵

Characterize the Taiwanese idiopathic inflammatory myositis cohort by hierarchical clustering

目的：本研究旨在建立一個臨床血清病理分類系統，包括16種肌炎特異性抗體/肌炎相關抗體，以對台灣南部的特發性發炎性肌病變患者進行次分類，重點關注臨床肌炎特徵和肌炎特異性抗體/肌炎相關抗體。此外，該研究擴展到次分類組別進行生存分析。
方法：這個研究收集來自一個醫學中心及兩個附屬醫院從2002年到2022總共108名特發性發炎性肌病變的成人病患。使用包括人口統計學、疾病表現、實驗室檢查和16種肌炎特異性抗體/肌炎相關抗體的數據集，通過生物信息學工具（如類別主成分分析和階層式分群算法）對患者進行次分類。該方法旨在將複雜的臨床數據濃縮為必要組成部分，從而找出獨特的患者次族群。
結果：該研究通過整合從2002年到2022總共108名病患臨床和分子特徵，找出具有獨特病理生理學特徵的特發性發炎性肌病變次族群（第3和第4群）並確認了傳統的特發性發炎性肌病變表型（第1和第6群）。生存分析強調了抗MDA5陽性患者有更高間質性肺病(ILD)的發病率和更差的整體生存率，這與文獻上無肌變型皮肌炎(CADM)的特徵相呼應。
結論：肌炎特異性抗體/肌炎相關抗體配置文件與臨床和分子特徵的整合促進了不同特發性炎性肌病亞群的識別。其中一些亞群呈現獨特的病理生理學特徵，值得進一步研究。此外，基於特定肌炎特異性抗體/肌炎相關抗體反應性的生存分析確認了抗MDA5陽性炎性肌病患者的嚴重預後，與文獻中關於抗MDA5陽性CADM的報導一致。

Objectives: This study aims to establish a clinico-seropathological classification system inclusive of 16 myositis specific antibodies (MSAs)/myositis associated antibodies (MAAs) to sub-classify patients from a southern Taiwanese cohort with idiopathic inflammatory myopathies (IIM), focusing on clinical myositis features and MSAs/MAAs. Additionally, the study extends to performing survival analysis on the subclassified groups.
Methods: This study includes 108 Taiwanese adults with defined IIM in our single center and two affiliated hospitals from 2002 to 2022. Using a dataset that includes demographics, disease manifestations, laboratory examinations, and 16 MSAs/MAAs, patients were sub-classified through bioinformatics tools such as categorical principal component analysis and hierarchical cluster algorithms. The methodology aimed to condense complex clinical data into essential components, allowing for the identification of unique patient subgroups.
Results: A total of 108 patients, from 2002 to 2022, were clustered into the unique IIM subgroups with distinct pathophysiological profiles (Clusters 3 and 4), and confirmed conventional IIM phenotypes (Clusters 1 and 6) by integrating clinical and molecular features. Survival analysis highlighted a higher incidence of interstitial lung disease (ILD) and poorer overall survival among anti–melanoma differentiation-associated gene 5 (anti-MDA5) positive IIM patients, echoing the clinically amyopathic dermatomyositis (CADM) characteristics.
Conclusion: The integration of MSAs/MAAs profiles with clinical and molecular features has facilitated the identification of distinct IIM subgroups. Some of these subgroups present unique pathophysiological characteristics that warrant further study. Additionally, survival analysis based on specific MSAs/MAAs reactivities has confirmed the severe prognosis for anti-MDA5 positive IIM patients, consistent with the literature on anti-MDA5 positive CADM.