Patients with rheumatoid arthritis have higher levels of mannan-binding lectin than their first-degree relatives and unrelated controls

Objective. Mannan-binding lectin (MBL) is present in serum and synovial fluid; its levels vary widely, and the variations are strongly associated with polymorphisms in the MBL2 gene. Studies have compared MBL in patients with rheumatoid arthritis (RA) and in unrelated controls, but the findings have been contradictory. In the first family-based study, we compared MBL levels in patients with RA to population controls and also to their nonaffected first-degree relatives, who may be regarded as optimal controls because of less genetic variation. Methods. Serum levels of MBL and rheumatoid factor were analyzed in 2 10 patients with RA and 406 of their first-degree relatives from 74 extended families. Population controls for MBL levels were 330 randomly selected adult Icelanders. Results. Patients with RA had higher MBL levels in serum (median 1553 mu g/l) than their first-degree relatives (1073 mu g/l; p = 0.003) and the unrelated controls (938 mu g/l; p < 0.0001). No association was found between MBL and rheumatoid factor. Conclusion. Patients with RA had markedly higher MBL levels than their close relatives and controls, indicating that high MBL may predispose to RA. As MBL has been shown to bind potential arthritogenic agents including modified immunoglobulins, cellular debris, and microorganisms, our findings suggest that high MBL could trigger complement mediated inflammation within joints.