Neonatal Fc receptor induces intravenous immunoglobulin growth suppression in Langerhans cell histiocytosis

Abstract

The neonatal Fc receptor (FcRn) plays a role in trafficking IgG and albumin and is thought to mediate intravenous immunoglobulin (IVIG) therapy for certain diseases. IVIG can be used for the treatment of human Langerhans cell histiocytosis (LCH); however, the mechanism remains unclear. The expression and function of FcRn protein have not been studied in LCH, though the expression of FcRn messenger RNA (mRNA) have been reported. In this report, we confirmed the expression of FcRn in 26 of 30 pathological cases (86.7%) diagnosed immunohistochemically as LCH. The expression was independent of age, gender, location, multi‐ or single‐system, and the status of BRAFV600E immunostaining. We also confirmed the expression of FcRn mRNA and protein in the human LCH‐like cell line, ELD‐1. FcRn suppressed albumin consumption and growth of IVIG preparation‐treated ELD‐1 cells, but not of IVIG preparation‐untreated or FcRn‐knockdown ELD‐1 cells. In addition, FITC‐conjugated albumin was taken into Rab11‐positive recycle vesicles in mock ELD‐1 cells but not in FcRn‐knockdown ELD‐1 cells. IVIG preparation prolonged this status in mock ELD‐1 cells. Therefore, ELD‐1 recycled albumin via FcRn and albumin was not used for metabolism. Our results increase our understanding of the molecular mechanism of IVIG treatment of LCH.