title: DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins.
abstract: IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear. In this study, we sought to identify the disease-associated genes, especially innate immune molecules. Gene expression was analyzed by DNA microarray in submandibular glands (SMGs) from patients with IgG4-RD (n = 5), chronic sialoadenitis (CS) (n = 3), and controls (n = 3). Differentially expressed genes (DEGs) were validated by real-time polymerase chain reaction (PCR) and immunohistochemical staining in IgG4-RD (n = 18), CS (n = 4), Sjögren syndrome (n = 11), and controls (n = 10). Gene expression patterns in the 3 groups were quite different from each other by the pvclust method and principal components analysis. In IgG4-RD, 1028 upregulated genes and 692 downregulated genes were identified as DEGs (P < 0.05). Gene Ontology (GO) term analysis indicated that the upregulated DEGs in IgG4-RD encoded proteins involved in T/B cell activation and chemotaxis. PCR validated significantly higher expression of macrophage receptor with collagenous structure (MARCO), a pattern-recognition receptor, in IgG4-RD compared with the other groups (P < 0.01). Immunohistochemical analysis confirmed that the expression pattern of MARCO was similar to that of the M2 macrophage marker CD163. MARCO was identified as a disease-associated molecule in IgG4-RD by DNA microarray. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO.
authors.affiliation: From the Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences (MO, MM, TM, SF, AT, J-NH, MY, NI, YM, SK, SN); OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan (MM); Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (YG, YS); Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (HT, MI-K); and Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University (TK), Fukuoka, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ohta
authors.forename: Masafumi
authors.initials: M
authors.lastname: Moriyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Maehara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Gion
authors.forename: Sachiko
authors.initials: S
authors.lastname: Furukawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Jun-Nosuke
authors.initials: JN
authors.lastname: Hayashida
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishiguro
authors.forename: Yurie
authors.initials: Y
authors.lastname: Mikami
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tsuboi
authors.forename: Mana
authors.initials: M
authors.lastname: Iizuka-Koga
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kawano
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sato
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kiyoshima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012793:Sialadenitis / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; C490460:MARCO protein, human; D011971:Receptors, Immunologic