PURPOSE: Type V hyperlipidemia (HTG V) characterized by accumulation of both chylomicrons and VLDL results from a complex combination of genetic and environmental factors. However, a large proportion of sporadic cases remains largely unexplained. In a few cases, in a context of autoimmunity, auto-antibodies inhibiting lipoprotein lipase (LPL) activity have been incriminated. To establish their contribution to common type V hyperlipidemia in subjects with no apparent evidence of autoimmune background, we systematically screened the presence of these antibodies and their inhibition properties. METHODS: Screening for circulating anti-human LPL immunoglobulin G (anti-hLPL IgG) was carried out by western blotting in 63 subjects with HTG V and 77 controls. Inhibition of lipolytic activity by plasma from these patients was measured ex vivo. RESULTS: Anti-hLPL IgG was detectable in plasma from both controls and subjects with HTG V. After establishment of a threshold value corresponding to the 95th percentile of the control population, 27% of subjects with HTG V were found to have abnormal antibody levels (P<0.001). Only plasma obtained from these hyperchylomicronemic subjects with a high level of anti-hLPL IgG inhibited triglyceride hydrolysis whereas plasma from controls or HTG subjects with normal anti-hLPL IgG levels had no inhibitory effect (-13.5+/-3.4% vs 1.6+/-3.4%; P=0.04). However, no correlation was observed between anti-hLPL IgG levels, inhibitory effect and plasma triglyceride concentration. CONCLUSION: High levels of anti-hLPL immunoreactivity could be detected in only one out of four adult patients with type V hyperchylomicronemia. Furthermore, only a minority of these subjects (less than 10%) displayed both high anti-hLPL IgG levels and substantial inhibition (>20%) of plasma lipolysis. These auto-antibodies, in this setting only, might contribute to the occurrence of a minority of sporadic type V dyslipidemia cases. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
PURPOSE:Type V hyperlipidemia (HTG V) characterized by accumulation of both chylomicrons and VLDL results from a complex combination of genetic and environmental factors. However, a large proportion of sporadic cases remains largely unexplained. In a few cases, in a context of autoimmunity, auto-antibodies inhibiting lipoprotein lipase (LPL) activity have been incriminated. To establish their contribution to common type V hyperlipidemia in subjects with no apparent evidence of autoimmune background, we systematically screened the presence of these antibodies and their inhibition properties. METHODS: Screening for circulating anti-humanLPL immunoglobulin G (anti-hLPL IgG) was carried out by western blotting in 63 subjects with HTG V and 77 controls. Inhibition of lipolytic activity by plasma from these patients was measured ex vivo. RESULTS: Anti-hLPL IgG was detectable in plasma from both controls and subjects with HTG V. After establishment of a threshold value corresponding to the 95th percentile of the control population, 27% of subjects with HTG V were found to have abnormal antibody levels (P<0.001). Only plasma obtained from these hyperchylomicronemic subjects with a high level of anti-hLPL IgG inhibited triglyceride hydrolysis whereas plasma from controls or HTG subjects with normal anti-hLPL IgG levels had no inhibitory effect (-13.5+/-3.4% vs 1.6+/-3.4%; P=0.04). However, no correlation was observed between anti-hLPL IgG levels, inhibitory effect and plasma triglyceride concentration. CONCLUSION: High levels of anti-hLPL immunoreactivity could be detected in only one out of four adult patients with type V hyperchylomicronemia. Furthermore, only a minority of these subjects (less than 10%) displayed both high anti-hLPL IgG levels and substantial inhibition (>20%) of plasma lipolysis. These auto-antibodies, in this setting only, might contribute to the occurrence of a minority of sporadic type V dyslipidemia cases. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
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