Chylomicronemia from GPIHBP1 autoantibodies

Area of Science:

• Endocrinology
• Immunology
• Lipid Metabolism

Background:

• Chylomicronemia can result from autoantibodies targeting glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1).
• GPIHBP1 is crucial for endothelial transport of lipoprotein lipase (LPL) to capillaries for triglyceride hydrolysis.
• Autoantibodies against GPIHBP1 disrupt LPL transport, leading to impaired lipolytic processing of triglyceride-rich lipoproteins.

Purpose of the Study:

• To review the clinical and laboratory findings of the GPIHBP1 autoantibody syndrome.
• To summarize the characteristics of 22 patients diagnosed with this condition.

Main Methods:

• Review of clinical data and laboratory findings from 22 patients with GPIHBP1 autoantibodies and chylomicronemia.
• Analysis of autoantibody levels, triglyceride levels, lipoprotein lipase (LPL) levels, and GPIHBP1 plasma levels.
• Assessment of associated autoimmune conditions and treatment outcomes, including response to rituximab.

Main Results:

• All 22 patients presented with GPIHBP1 autoantibodies and chylomicronemia; no correlation was found between triglyceride and autoantibody levels.
• A history of pancreatitis was common, and most patients showed evidence of autoimmune disease.
• Low plasma LPL levels were observed, consistent with impaired LPL delivery. IgA autoantibodies were universal, and IgG4 autoantibodies were present in 19 patients.
• Plasma GPIHBP1 levels were low in 17 patients due to immunoassay interference by autoantibodies, but high in five patients with low autoantibody interference.
• Successful treatment with rituximab led to the disappearance of GPIHBP1 autoantibodies and normalization of triglyceride and LPL levels in several patients.

Conclusions:

• The GPIHBP1 autoantibody syndrome is a distinct cause of unexplained chylomicronemia.
• The syndrome is frequently associated with other autoimmune conditions and pancreatitis.
• Consideration of GPIHBP1 autoantibody syndrome is warranted in patients with new-onset, unexplained chylomicronemia, and rituximab shows promise as a therapeutic option.