Serum free light chains of immunoglobulins as biomarkers for systemic sclerosis characteristics, activity and severity.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Humoral immunity and B cells are thought to play an important role in the pathophysiology of the disease. B cells are activated, produce specific autoantibodies and profibrotic cytokines. One way to assess B cell activation is to measure serum free light chains of immunoglobulins (sFLC) levels. We assess here sFLC levels in patients with systemic sclerosis (SSc) and their correlation with the disease characteristics, activity and severity. One hundred and thirty-four SSc patients were prospectively enrolled and compared to 401 age- and sex-matched healthy controls. sFLC levels were measured by a new quantitative immunoassay. sFLC levels were significantly higher in SSc patients than in healthy controls. sFLC levels correlated with modified Rodnan skin score and were independently associated with the presence of interstitial lung disease and its severity. In univariate analysis, sFLC levels correlated with SSc activity, as measured by the European Scleroderma Study Group activity index, and severity, as measured by the Medsger's total severity score. In multivariate analysis, beta2-microglobulin levels correlated with disease activity, BAFF levels with severity and sFLC with neither of these. Other B-cell activation biomarkers (IgG, IgA, beta2-microglobulin and BAFF) were independently correlated with sFLC. sFLC levels are elevated in SSc and are independently associated with lung disease and its severity. B-cell activation biomarkers, including sFLC, beta2-microglobulin and BAFF, correlate with disease severity and activity. These results further support the role of B cell activation in the pathophysiology of SSc.