Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis
Abstract
Background: B-cell activating factor of the tumour necrosis factor family (BAFF) plays a role in autoantibody production and is elevated in dermatomyositis (DM) and anti-Jo-1-positive polymyositis (PM). We investigated the inter-relationships between serum levels of BAFF, anti-Jo-1 autoantibodies, and disease activity.
Methods: Serum levels of BAFF and anti-Jo-1 antibodies measured by enzyme-linked immunosorbent assay (ELISA) were compared to levels of myoglobin, creatine kinase (CK), aminotransferases (alanine (ALT) and aspartate (AST)), C-reactive protein (CRP), and disease activity assessed by the Myositis Disease Activity Assessment Tool in 63 antiJo- 1 antibody-positive DM/PM patients. Serial serum samples collected at 2 (46 cases) and 3-5 time points (23 cases) were included.
Relationships between BAFF, anti-Jo-1, disease activity, CRP, and their longitudinal changes were evaluated using correlation analysis, multiple regression (MR), path analysis (PA), and hierarchical linear models (HLM). Results: Cross-sectional assessment demonstrated significant correlations between the levels of BAFF and anti-Jo-1 antibodies which were associated with levels of CK, myoglobin, AST, and CRP, as well as multivariate associations between BAFF, anti-Jo-1 antibodies, and CK levels.
PA revealed direct effects of anti-Jo-1 antibodies on CK (beta = 0.41) and both direct (beta = 0.42) and indirect (through anti-Jo-1 antibodies; beta = 0.17) effects of BAFF on CK. Changes in levels of both BAFF and anti-Jo-1 between two time points (Delta) were associated with Delta myoglobin and Delta aminotransferases and changes of BAFF correlated with Delta CK, Delta cutaneous,Delta muscle, Delta global, and Delta skeletal disease activities.
The longitudinal analysis showed a high intra-individual variability of serum levels of BAFF over time (97%) which could predict 79% of the variance in anti-Jo-1 levels. The anti-Jo-1 variability was explained by inter-individual differences (68%).
The close longitudinal relationship between levels of BAFF, anti-Jo-1, and disease activity was supported by high proportions of their variance explained with serum levels of CK and CRP or pulmonary and muscle activities. Conclusion: Our findings of associations between levels of BAFF and anti-Jo-1 antibodies in serum and myositis activity suggest a role of this cytokine in disease-specific autoantibody production as part of disease mechanisms, and support BAFF as a potential target for intervention in anti-Jo-1-positive myositis patients.