TY - JOUR

T1 - GPIHBP1 autoantibodies in a patient with unexplained chylomicronemia

AU - Hu, Xuchen

AU - Dallinga-Thie, Geesje M.

AU - Hovingh, G. Kees

AU - Chang, Sandy Y.

AU - Sandoval, Norma P.

AU - Dang, Tiffany Ly P.

AU - Fukamachi, Isamu

AU - Miyashita, Kazuya

AU - Nakajima, Katsuyuki

AU - Murakami, Masami

AU - Fong, Loren G.

AU - Ploug, Michael

AU - Young, Stephen G.

AU - Beigneux, Anne P.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Background GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the interstitial spaces and transports it to the capillary lumen. GPIHBP1 deficiency prevents LPL from reaching the capillary lumen, resulting in low intravascular LPL levels, impaired intravascular triglyceride processing, and severe hypertriglyceridemia (chylomicronemia). A recent study showed that some cases of hypertriglyceridemia are caused by autoantibodies against GPIHBP1 (“GPIHBP1 autoantibody syndrome”). Objective Our objective was to gain additional insights into the frequency of the GPIHBP1 autoantibody syndrome in patients with unexplained chylomicronemia. Methods We used enzyme-linked immunosorbent assays to screen for GPIHBP1 autoantibodies in 33 patients with unexplained chylomicronemia and then used Western blots and immunocytochemistry studies to characterize the GPIHBP1 autoantibodies. Results The plasma of 1 patient, a 36-year-old man with severe hypertriglyceridemia, contained GPIHBP1 autoantibodies. The autoantibodies, which were easily detectable by Western blot, blocked the ability of GPIHBP1 to bind LPL. The plasma levels of LPL mass and activity were low. The patient had no history of autoimmune disease, but his plasma was positive for antinuclear antibodies. Conclusions One of 33 patients with unexplained chylomicronemia had the GPIHBP1 autoantibody syndrome. Additional studies in large lipid clinics will be helpful for better defining the frequency of this syndrome and for exploring the best strategies for treatment.

AB - Background GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the interstitial spaces and transports it to the capillary lumen. GPIHBP1 deficiency prevents LPL from reaching the capillary lumen, resulting in low intravascular LPL levels, impaired intravascular triglyceride processing, and severe hypertriglyceridemia (chylomicronemia). A recent study showed that some cases of hypertriglyceridemia are caused by autoantibodies against GPIHBP1 (“GPIHBP1 autoantibody syndrome”). Objective Our objective was to gain additional insights into the frequency of the GPIHBP1 autoantibody syndrome in patients with unexplained chylomicronemia. Methods We used enzyme-linked immunosorbent assays to screen for GPIHBP1 autoantibodies in 33 patients with unexplained chylomicronemia and then used Western blots and immunocytochemistry studies to characterize the GPIHBP1 autoantibodies. Results The plasma of 1 patient, a 36-year-old man with severe hypertriglyceridemia, contained GPIHBP1 autoantibodies. The autoantibodies, which were easily detectable by Western blot, blocked the ability of GPIHBP1 to bind LPL. The plasma levels of LPL mass and activity were low. The patient had no history of autoimmune disease, but his plasma was positive for antinuclear antibodies. Conclusions One of 33 patients with unexplained chylomicronemia had the GPIHBP1 autoantibody syndrome. Additional studies in large lipid clinics will be helpful for better defining the frequency of this syndrome and for exploring the best strategies for treatment.

KW - Chylomicrons

KW - Endothelial cells

KW - Intravascular lipolysis

KW - Lipids

KW - Triglycerides

U2 - 10.1016/j.jacl.2017.05.017

DO - 10.1016/j.jacl.2017.05.017

M3 - Journal article

C2 - 28666713

AN - SCOPUS:85021838882

VL - 11

SP - 964

EP - 971

JO - Journal of Clinical Lipidology

JF - Journal of Clinical Lipidology

SN - 1933-2874

IS - 4

ER -