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2016 ; 95
(7
): e2853
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DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates
a Role for MARCO and Other Innate Immune-Related Proteins
#MMPMID26886650
Ohta M
; Moriyama M
; Maehara T
; Gion Y
; Furukawa S
; Tanaka A
; Hayashida JN
; Yamauchi M
; Ishiguro N
; Mikami Y
; Tsuboi H
; Iizuka-Koga M
; Kawano S
; Sato Y
; Kiyoshima T
; Sumida T
; Nakamura S
Medicine (Baltimore)
2016[Feb]; 95
(7
): e2853
PMID26886650
show ga
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.