Comparative B cell epitope profiling in Japanese and North American cohorts of MDA5+ dermatomyositis reveals a direct association between immune repertoire and pulmonary mortality.
Rheumatology (Oxford)
; 2024 Aug 26.
Article
en En
| MEDLINE
| ID: mdl-39186037
ABSTRACT
OBJECTIVES:
Anti-melanoma differentiation-associated gene 5 antibody-positive (MDA5+) dermatomyositis patients exhibit clinical features that vary by geographical and ethnic/genetic distribution. We therefore investigated whether B cell epitope profiles and corresponding clinical features distinguished two independent cohorts of MDA5+ dermatomyositis.METHODS:
We used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 17 MDA5+ dermatomyositis patients from Japan. Associations between clinical features and standardized anti-MDA5 subfragment antibody titers were assessed via Brunner Munzel testing and compared with clinical/serological profiles of an independent North American cohort. ROC analyses and Kaplan-Meier curves were used to further assess the relationship between anti-MDA5 fragment antibody levels and specific clinical features/outcomes.RESULTS:
Clinical characterization of a Japanese cohort of 17 MDA5+ dermatomyositis patients revealed a high prevalence of arthritis (47%) and interstitial lung disease (ILD) (100%). Serological profiling demonstrated predominant antibody recognition of MDA5 fragments A (aa 1-155), B (aa 130-284), and E (aa 517-671) in a pattern that was distinct from North American MDA5+ patients (n = 24) whose sera preferentially recognized fragment H (aa 905-1026). Statistical analysis revealed a striking association between anti-fragment A antibody levels and rapidly progressive ILD (RP-ILD) among Japanese patients (p< 0.01). ROC and Kaplan Meier curves also demonstrated a strong relationship between anti-fragment A antibody levels, RP-ILD, and pulmonary death in combined cohort analyses.CONCLUSIONS:
Japanese and North American MDA5+ dermatomyositis patients manifest markedly different B cell epitope profiles that are associated with higher prevalence of RP-ILD and worse clinical outcome among Japanese patients.
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Bases de datos:
MEDLINE
Idioma:
En
Revista:
Rheumatology (Oxford)
Asunto de la revista:
REUMATOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos