Developmental considerations of sperm protein 17 gene expression in rheumatoid arthritis synoviocytes.

Yuichi Takeoka,Mitsuru Naiki,Hisashi Yago,Thomas P Kenny,M Eric Gershwin,Dick L Robbins

doi:10.1080/1044667021000095186

Yuichi Takeoka, Mitsuru Naiki + Show 4 more

Open Access

https://doi.org/10.1080/1044667021000095186

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Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovial tissue. We used mRNA differential display and library subtraction to compare mRNA expression in RA and osteoarthritis (OA) synoviocytes. We initially compared the mRNA expression patterns in 1 female RA and 1 OA synovia and found a differentially expressed 350 bp transcript in the RA synoviocytes which was, by sequence analysis, 100% homologous to sperm protein 17 (Sp17). Moreover, the Sp17 transcript was found differentially expressed in a RA synovial library that was subtracted with an OA synovial library. Using specific primers for full length Sp17, a 1.1 kb transcript was amplified from the synoviocytes of 7 additional female RA patients, sequenced and found to 100% homologous to Sp17. Thus, we found the unexpected expression of Sp17, a thought to be gamete-specific protein, in the synoviocytes of 8/8 female RA patients in contrast to control OA synoviocytes. Interestingly, Sp17's structural relationship with cell-binding and recognition proteins, suggests that Sp17 may function in cell-cell recognition and signaling in the RA synoviocyte. Further, Sp17 could have a significant regulatory role in RA synoviocyte gene transcription and/or signal transduction. Thus, Sp17 could have an important role in RA synoviocyte proliferation or defective apoptosis. Finally, the presence of Sp17 in synoviocytes has interesting developmental considerations.

Highlights

Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovial tissue, including proliferating synoviocytes and subsynovial tissue infiltrated with lymphoid and other immune cells
We initially found the differential expression of sperm protein 17 (Sp17) mRNA using differential display and confirmed by library subtraction between a female RA patient’s and an OA patient’s synoviocytes
We designed specific 50 and coding region primers to amplify the remainder of the Sp17 gene from the RA synoviocytes

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovial tissue, including proliferating synoviocytes and subsynovial tissue infiltrated with lymphoid and other immune cells. T cells, B cells, macrophages, cytokines, MHC antigens and other gene products are important in RA as is synoviocyte proliferation and the subsequent destruction of articular cartilage and bone (Goronzy and Weyand, 1997; Imamura et al, 1998). Understanding the mechanisms responsible for synoviocyte hyperplasia, e.g. proliferation versus defective apoptosis, is necessary to better understand RA. Sperm protein (Sp17) is a highly conserved and autoantigenic protein that was originally cloned, sequenced and characterized as the 17 kD member of the rabbit sperm autoantigen family of Sp (O’Rand et al, 1988; Richardson et al, 1994). Recently Sp17 has been found in some lymphoid tissue and certain malignancies (Dong et al, 1997), suggesting that Sp17 belongs to a new family of molecules, the cancer-testes antigen (CTS)

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