Neonatal Fc receptor induces intravenous immunoglobulin growth
suppression in Langerhans cell histiocytosis
Abstract
BACKGROUND: 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 have not been
studied in LCH. METHODS: We evaluated the expression of FcRn in
pathological samples with LCH by Immunohistochemistry, and did in
LCH-like cell lines by RT-PCR and immunoblotting. Cell growth assay and
immunocytochemistry were employed to evaluate the FcRn function in the
LCH cell line in the presence or absence of albumin in the culture
medium. RESULTS: 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, but not in another LCH-like cell line PRU-1. IVIG
administration suppressed albumin-dependent cell growth of mock ELD-1
cells, but not of FcRn-knockdown ELD-1 cells. FITC-conjugated albumin
was taken into Rab11-positive recycle vesicles in mock ELD-1 cells, but
not in FcRn-knockdown ELD-1 cells. IVIG prolonged this status in mock
ELD-1 cells. CONCLUSION: ELD-1 recycled albumin via FcRn and albumin was
disused for cell growth. Our results increase our understanding of the
molecular mechanism of IVIG treatment of LCH.