FCN1 (M-ficolin), which directly associates with immunoglobulin G1, is a molecular target of intravenous immunoglobulin therapy for Kawasaki disease

• Published in: Scientific reports 2017-09, Vol.7 (1), p.11334-12, Article 11334
• Main Authors: Okuzaki, Daisuke, Ota, Kaori, Takatsuki, Shin-ichi, Akiyoshi, Yukari, Naoi, Kazuyuki, Yabuta, Norikazu, Saji, Tsutomu, Nojima, Hiroshi
• Format: Article
• Language: English
• Subjects: 38; 38/39; 38/61; 631/45/881; 692/308/3187; 692/4023/1670; Children; Collagen; Complement system; Computational Biology - methods; DNA microarrays; Etiology; Female; Ficolins; Gene Expression Profiling; Humanities and Social Sciences; Humans; Immunoglobulin G; Immunoglobulin G - chemistry; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Immunoglobulins; Immunoglobulins, Intravenous - therapeutic use; Intravenous administration; Kawasaki disease; Lectins - chemistry; Lectins - genetics; Lectins - immunology; Lectins - metabolism; Leukocytes (mononuclear); Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; M-ficolin; Male; Monoclonal antibodies; mRNA; Mucocutaneous lymph node syndrome; Mucocutaneous Lymph Node Syndrome - genetics; Mucocutaneous Lymph Node Syndrome - immunology; Mucocutaneous Lymph Node Syndrome - metabolism; Mucocutaneous Lymph Node Syndrome - therapy; multidisciplinary; Oligonucleotide Array Sequence Analysis; Peptides; Peripheral blood mononuclear cells; Protein Binding; Protein Interaction Domains and Motifs; Real-Time Polymerase Chain Reaction; Science; Science (multidisciplinary); Synthetic peptides; Systemic vasculitis; Transcriptome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11108-0

Kawasaki disease (KD), an acute systemic vasculitis of early childhood, is of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is an effective treatment, but its molecular target remains elusive. DNA microarray analysis of peripheral blood mononuclear cells (PBMCs) revealed that at least 21 genes are drastically down-regulated after IVIG treatment in most KD patients. qRT-PCR analysis confirmed that the mRNA levels of five of these genes were considerably reduced in almost all KD patients after IVIG treatment. Western blot (Wb) of PBMC extracts revealed that levels of FCN1 (M-ficolin), a protein of the complement system that defends against infectious agents, were reduced after IVIG treatment in many KD patients. In another set of KD patients, Wb confirmed that levels of both FCN1 were greatly reduced after IVIG therapy. Wb revealed that the collagen-like domain of FCN1 directly bound to IgG1 in vitro through a portion of the CH1 and CH3 domains, and synthetic peptides corresponding to these domains of IgG1 efficiently inhibited these associations. These results suggest that FCN1 is a molecular target of intravenous IVIG in KD patients. We propose that these peptides and a humanized monoclonal antibody against FCN1 could be useful in combination therapy with IVIG.