Frontiers in immunology · 2025
The clinical utility of autoantibodies in systemic sclerosis: a review with a focus on cohort differences and standardization.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Komura Kazuhiro
Аннотация
BACKGROUND: Systemic sclerosis (SSc) is clinically heterogeneous. Disease-specific autoantibodies-anticentromere (ACA), anti-topoisomerase I (ATA/Scl-70), and anti-RNA polymerase III (RNAP III)-are central to classification and organ-risk prediction. Beyond prognosis, SSc-specific autoantibodies can support diagnosis as part of a composite assessment with nailfold capillaroscopy and clinical features; their contribution is reflected in the 2013 ACR/EULAR classification criteria and can be informative in very-early or sine presentations. More broadly, these immune signatures underpin routine SSc care and underscore the immunological impacts that shape disease expression.
METHODS: Narrative review (2000-August 2025) prioritizing studies in Japanese and Western cohorts, with emphasis on assay performance and cohort comparability. We appraise line immunoassay (LIA) performance vis-à-vis immunoprecipitation (IP), and integrate ICAP-compliant ANA interpretation.
RESULTS: ACA aligns with lower ILD risk but higher PAH and digital vasculopathy; ATA predicts ILD onset/progression; RNAP III marks rapid skin thickening, SRC risk, and temporally clustered malignancy; U1 RNP tracks overlap/MCTD-like features and PAH; U3 RNP indicates diffuse disease with vasculopathy; Th/To varies by center; PM-Scl and Ku flag overlap ILD/myositis. A clinical-first standardized workflow-ANA (ICAP) + core ELISAs (ACA, ATA, RNAP III, U1 RNP) followed by ANA-pattern-guided LIA/IP confirmation-supports both care and cross-cohort comparability.
CONCLUSIONS: Autoantibodies form a practical foundation for SSc care across regions. Standardizing the reflex layer (LIA/IP) while leveraging established ANA and core ELISAs can reduce measurement-driven cohort differences and improve global synthesis of SSc evidence.
METHODS: Narrative review (2000-August 2025) prioritizing studies in Japanese and Western cohorts, with emphasis on assay performance and cohort comparability. We appraise line immunoassay (LIA) performance vis-à-vis immunoprecipitation (IP), and integrate ICAP-compliant ANA interpretation.
RESULTS: ACA aligns with lower ILD risk but higher PAH and digital vasculopathy; ATA predicts ILD onset/progression; RNAP III marks rapid skin thickening, SRC risk, and temporally clustered malignancy; U1 RNP tracks overlap/MCTD-like features and PAH; U3 RNP indicates diffuse disease with vasculopathy; Th/To varies by center; PM-Scl and Ku flag overlap ILD/myositis. A clinical-first standardized workflow-ANA (ICAP) + core ELISAs (ACA, ATA, RNAP III, U1 RNP) followed by ANA-pattern-guided LIA/IP confirmation-supports both care and cross-cohort comparability.
CONCLUSIONS: Autoantibodies form a practical foundation for SSc care across regions. Standardizing the reflex layer (LIA/IP) while leveraging established ANA and core ELISAs can reduce measurement-driven cohort differences and improve global synthesis of SSc evidence.