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An Exploratory Analysis of Antibody Dynamics in Isolated Organ Involvement of Antisynthetase Syndrome: A
Takeshi Suzuki1, Misa Yamaji2, Hiroaki Harada2
1Division of Rheumatology and Allergology, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan.
Objective:
To characterize longitudinal anti-aminoacyl-tRNA synthetase (anti-ARS) antibody kinetics in antisynthetase syndrome (ASyS) with isolated organ involvement (IOI) and examine associations with clinical trajectories versus multiple organ involvement (MOI).
Methods:
We retrospectively analyzed 23 patients with ASyS with serial anti-ARS antibody measurements (IOI, n = 12; MOI, n = 11). IOI was defined as involvement of a single organ domain, whereas MOI involved ≥2 domains. Anti-ARS antibody titers were measured using a five-antibody enzyme-linked immunosorbent assay panel. Cumulative antibody burden was quantified as area under the curve (AUC) normalized by observation time. Longitudinal trajectories were evaluated using a linear mixed-effects model.
Results:
Baseline anti-ARS antibody titers were lower in IOI than MOI (median 84.1 [interquartile range (IQR) 57.6-117.5] vs median 163.0 [IQR 132.0-175.5]; P = 0.007). Among treated patients with longitudinal data (IOI, n = 7; MOI, n = 10), IOI exhibited a more consistent decline and lower cumulative exposure (normalized AUC: median 33.7 [IQR 32.5-61.7] vs median 103.0 [IQR 94.1-144.0]; P < 0.001). Population-level trajectories showed a steeper decline in IOI, with a significant group-time interaction (P = 0.026). In IOI, antibody reductions were concordant with KL-6 improvement and radiologic findings, and prednisolone tapering or discontinuation was achieved without relapse.
Conclusion:
IOI was associated with lower baseline anti-ARS antibody titers and a more pronounced decline versus MOI. These findings support a stage-based framework in which IOI represents a phase with limited organ involvement. The integrated kinetic pattern-lower baseline titers, steeper decline, and lower cumulative exposure-may be associated with a more favorable treatment-associated clinical course.
