CONTEXT: Sporadic hyperchylomicronemia (type V hyperlipoproteinemia) results from complex interactions between genetic and environmental factors that often remain unknown. DESIGN: Upon investigation of a patient suffering from recurrent hypertriglyceridemic pancreatitis without family history or conventional secondary cause of dyslipidemia, we identified a previously unreported nonsense heterozygous lipoprotein lipase (LPL) gene mutation S172fsX179 associated with an antihuman LPL IgG. RESULTS: This autoantibody partially inhibited wild-type LPL activity in vitro. Furthermore, the patient's plasma triglyceride concentrations were efficiently decreased under immunosuppressive treatment, and this was confirmed by sequential withdrawal/reintroduction tests. CONCLUSIONS: We consider that this unique combination of a genetic defect and an autoimmune disease results in chronic major hypertriglyceridemia. Because immunosuppressive treatment can improve this dyslipidemia, assessment of anti-LPL autoantibody is worthwhile in unmanageable chronic major hypertriglyceridemia, even in the presence of a heterozygous LPL deficiency.
CONTEXT: Sporadic hyperchylomicronemia (type V hyperlipoproteinemia) results from complex interactions between genetic and environmental factors that often remain unknown. DESIGN: Upon investigation of a patient suffering from recurrent hypertriglyceridemic pancreatitis without family history or conventional secondary cause of dyslipidemia, we identified a previously unreported nonsense heterozygous lipoprotein lipase (LPL) gene mutation S172fsX179 associated with an antihuman LPL IgG. RESULTS: This autoantibody partially inhibited wild-type LPL activity in vitro. Furthermore, the patient's plasma triglyceride concentrations were efficiently decreased under immunosuppressive treatment, and this was confirmed by sequential withdrawal/reintroduction tests. CONCLUSIONS: We consider that this unique combination of a genetic defect and an autoimmune disease results in chronic major hypertriglyceridemia. Because immunosuppressive treatment can improve this dyslipidemia, assessment of anti-LPL autoantibody is worthwhile in unmanageable chronic major hypertriglyceridemia, even in the presence of a heterozygous LPL deficiency.
Authors: Anne P Beigneux; Kazuya Miyashita; Michael Ploug; Dirk J Blom; Masumi Ai; MacRae F Linton; Weerapan Khovidhunkit; Robert Dufour; Abhimanyu Garg; Maureen A McMahon; Clive R Pullinger; Norma P Sandoval; Xuchen Hu; Christopher M Allan; Mikael Larsson; Tetsuo Machida; Masami Murakami; Karen Reue; Peter Tontonoz; Ira J Goldberg; Philippe Moulin; Sybil Charrière; Loren G Fong; Katsuyuki Nakajima; Stephen G Young Journal: N Engl J Med Date: 2017-04-05 Impact factor: 91.245
Authors: Kazuya Miyashita; Jens Lutz; Lisa C Hudgins; Dana Toib; Ambika P Ashraf; Wenxin Song; Masami Murakami; Katsuyuki Nakajima; Michael Ploug; Loren G Fong; Stephen G Young; Anne P Beigneux Journal: J Lipid Res Date: 2020-09-18 Impact factor: 5.922