Characterization of a New Case of Autoimmune Type I Hyperlipidemia: Long-Term Remission under Immunosuppressive Therapy* VALERIE PRUNETA, PHILIPPE MOULIN†, FLORENCE LABROUSSE, PIERRE-JEAN BONDON, GABRIEL PONSIN, AND FRANCOIS BERTHEZENE Laboratoire de Me ´tabolisme des Lipides (V.P., P.M., G.P.), Service d’Endocrinologie et des Maladies de la Nutrition (F.L., F.B.), and Laboratoire de Biochimie (P.B.), Ho ˆpital de l’Antiquaille, Lyon, France ABSTRACT Only a few cases of type I hyperlipidemia occurring in patients with autoimmune disease have been reported. We describe the case of a 35-yr-old woman suffering from severe type I hyperchylomicronemia. A combination of various hypolipidemic treatments, including strict hypolipidemic dietary therapy and administration of fibrates or n-3 fatty acids, was inefficient. Because of a history of familial autoim- munity, we introduced an immunosuppressive therapy that resulted in consistent long term and stable remission. Two attempts to reduce the immunosuppressor dose resulted in major relapses. To explain the defect of chylomicron hydrolysis, we investigated the postheparin plasma lipase activities. Hepatic triglyceride lipase activity was nor- mal, whereas that of lipoprotein lipase (LPL) was reduced to about 30% of normal. Immunosuppressive therapy resulted in a complete and durable normalization of LPL activity. Using Western blot anal- ysis, we found in the plasma of the patient a circulating IgG specif- ically directed against LPL, which became undetectable during im- munosuppressive therapy. Western blot analysis revealed that the whole circulating anti-LPL autoantibody was bound to chylomicrons. Proteins extracted from patient’s chylomicrons were able to induce a dose-related inhibition of LPL activity in vitro, whereas that of he- patic triglyceride lipase remained unchanged. These data constitute the first description of autoimmune hyper- chylomicronemia due to an exclusive defect of LPL activity, and they show that a complete remission has been obtained after immunosup- pressive therapy. Finally, our finding that the anti-LPL autoantibody is bound to chylomicrons emphasizes their previously unrecognized ability to transport LPL, already described for other lipoprotein frac- tions. (J Clin Endocrinol Metab 82: 791–796, 1997) T YPE I HYPERLIPIDEMIA is characterized by a major hypertriglyceridemia due to an exclusive accumula- tion of chylomicrons in plasma (1). This infrequent lipopro- tein phenotype is associated with a decrease in the ability of lipoprotein lipase (LPL; EC 3.1.1.34) to hydrolyze the tri- glycerides (TG) transported in chylomicrons and very low density lipoproteins (VLDL). Several reports have shown that type I hyperlipidemia generally results from gene mu- tations that may affect either LPL or apolipoprotein C-II (apo C-II), its physiological activator (2, 3). In contrast, secondary type I hyperlipidemia is extremely rare (4). The concept of autoimmune hyperlipidemia was first pro- posed by Beaumont in 1970 (5, 6). Only a few reports have described the occurrence of type I hyperchylomicronemia in an autoimmune context (7–9). However, in two of these studies, no attempt was made to characterize the specificity of the interaction between autoantibodies and plasma lipases (7, 8). More recently, a patient was reported to develop au- toimmune type I hyperchylomicronemia in association with idiopathic thrombocytopenic purpura and Graves’ disease (9). In this case, the hyperchylomicronemia was attributed to the presence of well characterized autoantibodies directed against both LPL and hepatic triglyceride lipase (HTGL), identified as IgA. We have diagnosed a case of severe autoimmune type I hyperchylomicronemia that was not associated with any other autoimmune disease despite a familial context of au- toimmunity. In the present study we describe the character- ization and the circulating form of the autoantibody respon- sible for the hyperchylomicronemia together with the effects of immunosuppressive therapy. Subjects and Methods Case report A 35-yr-old woman (D.E.; 52 kg; 162 cm) was admitted to our lipid clinic for recurrent major hypertriglyceridemia that resisted dietary treatment. She had a lipid phenotype of type I hyperlipidemia charac- terized by the presence in fasting samples of abundant chylomicrons together with normal VLDL abundance. A routine plasma lipid mea- surement showed no abnormalities when she was 26 yr old. She gave a history of poorly documented increase in the plasma TG concentration dating from several years, accompanied by recurrent episodes of un- diagnosed abdominal pain. After admission, she needed iterative plas- mapheresis for major bursts of hypertriglyceridemia (TG, 50 mmol/L) during the first months of follow-up (Fig. 1). An apo C-II deficiency was excluded on the basis of three consider- ations. Firstly, she had an elevated apo C-II level (Table 1). Secondly, fresh plasma exchanges had no hypolipidemic effect. Finally, her plasma had a normal ability to activate control LPL in vitro. No common causes that could induce a decrease in plasma lipolytic activity were found; she had no diabetes (fasting plasma glucose, 4.5 mmol/L), and her thyroid Received July 23, 1996. Revision received November 13, 1996. Ac- cepted December 2, 1996. Address all correspondence and requests for reprints to: Dr. Vale ´rie Pruneta, Laboratoire de Me ´tabolisme des Lipides, Ho ˆ pital de l’Antiquaille, 1 rue de l’Antiquaille, 69005 Lyon, France. * Presented in part at the 18th Annual Meeting of the European Lipoprotein Club, Tutzing, September 1995. This work was supported by grants from INSERM, the Hospices Civils de Lyon, and Fournier Laboratories. † Recipient of a fellowship from INSERM and Hospices Civils de Lyon. 0021-972X/97/$03.00/0 Vol. 82, No. 3 Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society 791 Downloaded from https://academic.oup.com/jcem/article-abstract/82/3/791/2656302 by guest on 30 May 2020