Successful Rituximab Treatment of GPIHBP1 Autoantibody-Associated Hypertriglyceridemia

Area of Science:

• Endocrinology
• Immunology
• Genetics

Background:

• A 50-year-old female presented with severe hypertriglyceridemia (up to 1640 mg/dL) and recurrent pancreatitis.
• Standard treatments including fenofibrate, icosapent ethyl, rosuvastatin, and diet were ineffective, with triglyceride levels escalating to over 8200 mg/dL.

Observation:

• Genetic testing excluded mutations in common chylomicronemia genes (LPL, APOC2, APOA5, LMF1, GPIHBP1).
• Elevated autoantibodies against Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and critically low GPIHBP1 levels confirmed GPIHBP1 autoantibody syndrome (GPIHBP1-AAS).

Findings:

• The patient received two 1000 mg doses of rituximab, 3 weeks apart.
• Triglyceride levels dramatically decreased from 1746 mg/dL to 81 mg/dL within 4 months post-treatment.
• Normal triglyceride levels were maintained for 12 months without further intervention.

Implications:

• GPIHBP1-AAS is a recently identified cause of severe hypertriglyceridemia and pancreatitis.
• Rituximab demonstrates significant efficacy in treating GPIHBP1-AAS, offering a novel therapeutic option for this rare condition.