Anti-mitochondrial antibodies as markers of disease activity in childhood-onset systemic lupus erythematosus: a longitudinal cohort study

Objectives: Mitochondria are prominent antigenic sources, capable of triggering IFN-induced inflammatory pathways in SLE. Recent studies suggest presence of AMA in LN patients with adult-onset SLE. Whether AMA reflect disease activity in childhood-onset SLE (cSLE) remains unexplored. Here, we present inaugural data on the potential utility of AMA as a biomarker in cSLE. Methods: Human mitochondria were incubated with serum, and IgG, IgM and IgA binding assessed by flow cytometry. Sera were obtained prospectively from 29 cSLE patients, at two different timepoints (TP), the first (TP-1) representing a state of active disease (SLEDAI >= 4), and the second (TP-2), of clinically quiescent disease (SLEDAI <= 4). IFN alpha 2 serum levels were assessed by single-molecule array. Results: Median age at disease diagnosis was 14.9 +/- 3.6 years. Median SLEDAI and prednisone dose were 9.5 and 0.43 mg/kg/day at TP-1, and 2 and 0.14 mg/kg/day at TP-2. Median time interval between TP-1 and TP-2 was of 6 +/- 3.7 months. AMA-IgG decreased between TP-1 and TP-2 (P = 0.0426), and correlated positively with SLEDAI (rho = 0.41, P = 0.026) and anti-dsDNA (rho = 0.66, P = 0.0001) at TP-1. AMA-IgM oscillated according to disease activity (P = 0.0065), while AMA-IgA remained stable. AMA-IgG and -IgM correlated with IFN alpha 2 levels (rho = 0.729, P < 0.0001, and rho = 0.631, P = 0.001, respectively) during active disease. Conclusion: AMA-IgG emerges as a promising biomarker of disease activity in cSLE, and its increase is in alignment with elevated IFN alpha 2 expression.