Evidence of Immunological Abnormalities in Sitosterolemia

Abstract

Objectives: Mutations involving the ABCG8 gene cause sitosterolemia (STSL), a rare metabolic disease due to an abnormal plasmatic plant sterols level. STSL hematological findings include stomatocytic hemolysis and macrothrombocytopenia. So far, few cases of leukopenia have been reported and there are no studies that consider inflammatory activity. The purpose of our study is to evaluate immunological abnormalities in STSL and the effect of dietary and pharmacological treatment. Study Design: In a sitosterolemic patient presenting leukopenia and increased inflammatory indexes were evaluated in vitro interleukin 1B secretion from monocytes and type 1 interferon (IFN) signature. Besides, Stimulation Indexes (SI) of patient’s and two Healthy Controls’ (HCs) T-helper lymphocytes in response to proliferative stimuli were assessed, when incubated in enriched medium alternately with patient plasma or with AB Rh+ group control plasma. SI (compared to the same HCs) and IFN signature have been evaluated again three (T3) and six (T6) months apart, after patient received therapy. Results: Following treatment with Ezetimibe (EZE) and adequate diet, lower plasmatic plant sterols levels and progressive improvement of hematological and immunological abnormalities were observed. These data were confirmed by the negativization of IFN signature at T3 and by the progressive normalization at T3 and T6 of SI in patient’s and HCs’ T-helper lymphocytes incubated in patient’s plasma-enriched medium. Conclusion: High plasmatic phytosterols levels due to STSL seems to affect white blood cells proliferation and trigger pro-inflammatory process, justifying leukopenia and increased phlogosis indexes observed in our patient. These hypotheses are supported by normalization of clinical and laboratory data during EZE therapy. Take-home Message: Immunological abnormalities should be considered among the hematological manifestations of sitosterolemia, moreover high levels of plasma phytosterols could be a pro-inflammatory trigger. Treatment with ezetimibe seems to reverse these manifestations.