Abstract
Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptome analysis was performed to identify genes over- and under-expressed in patients with IgG4-RD.
Method: DNA microarray analysis was performed using RNA from peripheral blood mononuclear cells of two patients with IgG4-RD and four healthy individuals. Genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy were identified. Four genes related to innate immunity such as transcobalamin I (TCN1), secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability-increasing protein (BPI) and lactotransferrin (LTF) were assessed by real-time PCR in 15 IgG4-RD patients and 13 healthy individuals.
Result: DNA microarray analysis identified 30 genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy. Real-time RT-PCR showed that the levels of mRNAs encoding TCNI and SLPI, except for BPI and LTF, were significantly lower in patients with IgG4-RD than in healthy people. The levels of all four mRNAs in patients with IgG4-RD were significantly increased after steroid treatment.
Conclusion: These results indicate that reduction in expression of innate immunity-related genes may participate in the pathogenesis of IgG4-RD that steroid treatment may rectify impaired innate immunity as well as acquired immunity.
Author contributions
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.
Dr. Umehara had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design: Nakamura, Satoh-Nakamura, Nakajima, Kawanami, Umehara. Acquisition of data: Sakai, Fujita, Iwao, Miki, Masaki, Okazaki, Yamada, Matsui, Saeki, Kamisawa, Yamamoto, Hamano, Origuchi, Hirata, Tanaka, Tsuboi, Sumida, Tanaka.
Analysis and interpretation of data: Ishigaki, Kawano, Okazaki, Chiba, Mimori, Umehara.
Conflict of interest
None.