A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease.

Kyotaro Ohno,Katsuyoshi Takata,Tomoyasu Tachibana,Tomoko Miyata-Takata,Toshihiro Ito,Yasuharu Sato,Mai Takeuchi,Steven H Swerdlow,Koh-Ichi Ohshima,Yuka Gion,Tadashi Yoshino,Yorihisa Orita

doi:10.1038/srep13539

Abstract

We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin, and FOXP3/β-actin than did IgG4-negative MZL (p < 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis.

Highlights

Diagnosis IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL
Most extranodal MZLs express high levels of CXCR3, which is the receptor for IFN-γ -induced chemokines[24,25,26]
39% of cutaneous MZLs with plasmacytic differentiation are reported to be IgG4+, whereas an ocular MZL was the only non-cutaneous IgG4+ MZL found in the same study[16]

Summary

Introduction

Diagnosis IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4-RD IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4− MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL IgG4+ MZL. The expression pattern of cytokines in MZL lesions with IgG4+ plasma cells has not been clarified. In this study of ocular IgG4-RD and MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells, we aimed to identify the mRNA expression patterns of Th2 and Treg cytokines and to determine the inflammatory background associated with benign and neoplastic ocular lymphoplasmacytic proliferations with numerous IgG4+ plasma cells that is distinct from that associated with ocular IgG4-negative MZL

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Conclusion