The CD4+CD52low T Cell Contributes to Disease Activity and Autoantybody Production in Systemic Lupus Erythematosus

Masataka Umeda¹, Tomohiro Koga¹, Kunihiro Ichinose², Toru Michitsuji¹, Toshimasa Shimizu², Shoichi Fukui³, Ayako Nishino³, Yoshikazu Nakashima⁴, Yoshiro Horai¹, Takahisa Suzuki¹, Shin-ya Kawashiri³, Naoki Iwamoto¹, Toshiyuki Aramaki⁵, Mami Tamai¹, Yasuko Hirai¹, Hideki Nakamura¹, Kazuo Yamamoto⁶, Tomoki Origuchi^7,8, Yukitaka Ueki⁹ and Atsushi Kawakami¹, ¹Department of Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan, ²Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ³Department of Immunology and Rheumatology, Nagasaki University, Nagasaki, Japan, ⁴Department of Rheumatology, Nagasaki University, Nagasaki, Japan, ⁵Department of Rheumatology, Sasebo Chuo Hospital, Sasebo, Japan, ⁶Biomedical Research Support Center, Nagasaki University School of Medicine, Nagasaki, Japan, ⁷Department of Rehabilitation Sciences, Nagasaki University, Nagasaki, Japan, ⁸Department of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁹Kyushu multicenter rheumatoid arthritis ultrasound prospective observational cohort study group, Nagasaki, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: T cells and systemic lupus erythematosus (SLE)

Session Information

Date: Tuesday, November 10, 2015

Title: T cell Biology and Targets in Autoimmune Disease Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: CD52
is a cell-surface glycoprotein that is widely expressed in lymphocytes,
monocytes and eosinophils. The anti-CD52 antibody has been used to treat
multiple autoimmune diseases, and its effectiveness has been reported. CD4⁺CD52^high
T cells inhibit the activation of CD4⁺CD52^low T cells
through the release of cell-surface CD52. Soluble CD52, which is cleaved from
CD4⁺CD52^high T cells, works as a ligand of siglec-10 on
CD4⁺CD52^low T cells (Nat Immunol. 2013 Jul;14(7):741-8.).
CD4⁺CD52^high T cells were reported as distinct population
from conventional regulatory T cells. The role of the immune regulation of CD4⁺CD52^high
T cells in systemic lupus erythematosus (SLE) is unknown.
We evaluated the CD4⁺CD52^high and CD4⁺CD52^low
T cells in the human peripheral blood mononuclear cells (PBMCs) of SLE patients
and clarified their roles in the pathogenesis of SLE.

Methods: We isolated the PBMCs of 40 SLE
patients, 14 non-SLE patients (11 with rheumatoid arthritis, 3 with mixed
connective-tissue disease) and 22 healthy controls (HCs). The expressions of
CD4⁺CD25⁺CD127^– T cells (Tregs), CD4⁺CD52^high
T cells and CD4⁺CD52^low T cells were analyzed by flow
cytometry. We also analyzed the correlations with clinical parameters including
SLEDAI, anti-ds-DNA antibody titer and complement titer. The soluble CD52 was
also analyzed in an ELISA among the SLE and non-SLE patients and HCs.

Results: We found that the expression of CD4⁺CD52^low
T cells in the SLE patients was significantly higher than HC (p=0.003) and
non-SLE (p=0.003) (Figure). The expression of CD4⁺CD52^low
T cells of the SLE group were significantly correlated with SLEDAI
(p-value=0.002, r=0.481803), anti-ds-DNA antibody (p-value=0.01, r=0.420842)
and IgG (p-value=0.018, r=0.392004). Soluble CD52 measured by ELISA was found
to be decreased in the SLE group versus the other groups (vs. HC: p=0.001; vs.
non-SLE: p=0.014). No significant difference
was found in the population of CD4⁺CD25⁺ CD127^–
cells among the groups. There was no correlation between Tregs and CD4⁺CD52^high
T cells in SLE.

Conclusion: Collectively, our data suggest
that increased CD4⁺CD52^low T cells along with decreased
soluble CD52 are involved in the pathogenic autoantibodies production
highlighting its potential as a therapeutic
target for SLE.

Disclosure: M. Umeda, None; T. Koga, None; K. Ichinose, None; T. Michitsuji, None; T. Shimizu, None; S. Fukui, None; A. Nishino, None; Y. Nakashima, None; Y. Horai, None; T. Suzuki, None; S. Y. Kawashiri, None; N. Iwamoto, None; T. Aramaki, None; M. Tamai, None; Y. Hirai, None; H. Nakamura, None; K. Yamamoto, None; T. Origuchi, None; Y. Ueki, None; A. Kawakami, None.

To cite this abstract in AMA style:

Umeda M, Koga T, Ichinose K, Michitsuji T, Shimizu T, Fukui S, Nishino A, Nakashima Y, Horai Y, Suzuki T, Kawashiri SY, Iwamoto N, Aramaki T, Tamai M, Hirai Y, Nakamura H, Yamamoto K, Origuchi T, Ueki Y, Kawakami A. The CD4+CD52low T Cell Contributes to Disease Activity and Autoantybody Production in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-cd4cd52low-t-cell-contributes-to-disease-activity-and-autoantybody-production-in-systemic-lupus-erythematosus/. Accessed .

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