Kodera_2005_J.Rheumatol_32_629

OBJECTIVE: The vascular damage systemic sclerosis (SSc) consists mainly of microvascular changes, but recently macrovascular changes with dyslipidemia were recognized. In systemic lupus erythematosus (SLE), autoantibody to lipoprotein lipase (LPL), a key enzyme that hydrolyzes triglycerides, suggested a role of autoimmunity for elevated serum triglyceride levels and atherosclerosis. We investigated the prevalence and levels of anti-LPL antibodies, their clinical correlation, and their functional significance in patients with SSc.
METHODS: Serum samples from patients with diffuse cutaneous SSc (dSSc; n = 55), limited cutaneous SSc (lSSc; n = 75), SLE (n = 21), and dermatomyositis (DM; n = 21) and healthy controls (n = 41) were examined by ELISA. The presence of anti-LPL antibody was evaluated by immunoblotting analysis using purified LPL. To determine the functional relevance of anti-LPL antibody in vivo, we assessed whether anti-LPL autoantibody was able to inhibit LPL activity using the LPL activity kit.
RESULTS: ELISA revealed that IgG or IgM anti-LPL antibodies were detected in 35% of SSc patients, while they were also positive in 67% of SLE patients and 43% of DM patients. The presence of IgG anti-LPL antibody was associated with elevated serum triglyceride levels, greater extent of skin fibrosis, and more frequent presence of lung fibrosis, heart involvement, and anti-topoisomerase I antibodies. The presence of anti-LPL autoantibody was confirmed by immunoblotting analysis. LPL activity was inhibited by IgG anti-LPL antibodies in sera from SSc patients with elevated serum triglyceride levels. CONCLUSION: Our results suggest that anti-LPL autoantibody contributes to elevated serum triglyceride levels by inhibiting LPL enzyme activity in patients with SSc.