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Abstract Number: 2861

Proportions of Circulating Follicular Helper T Cells and Complement Levels, White Blood Cell Counts, and Skin Manifestations in Patients with Active Systemic Lupus Erythematosus

Jun Kikuchi1, Masaru Takeshita1, Katsuya Suzuki2, Yoshiaki Kassai3, Takahiro Miyazaki3 and Tsutomu Takeuchi2, 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2Keio University School of Medcine, Division of Rheumatology, Department of Internal Medicine, Tokyo, Japan, 3Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Kanagawa, Japan

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: B cells, Plasmablasts, SLE and T cells

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Session Information

Date: Tuesday, November 15, 2016

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis - Poster II

Session Type: ACR Poster Session C

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

Background/Purpose:  Although circulating B cells and T cells, including follicular helper T (Tfh) cells, are reported to be involved in systemic lupus erythematosus (SLE) 1,2), relations between subpopulations and clinical manifestations have not been clearly determined. The aim of this study was to identify abnormalities of the subpopulations in correlation with clinical manifestations in active SLE patients.

Methods:  Subsets of peripheral immune cells were quantified using a whole blood flow cytometry in total 51 subjects including 13 active SLE patients who all fulfilled ACR classification criteria and 38 normal healthy controls (NHCs). We compared the proportions of the subsets in SLE patients with those in NHCs and analyzed relations with the clinical parameters.

Results:  Mean age of the SLE patients and NHCs was 44.1 and 39.8 years, respectively. All candidates were female. Mean SLE Disease Activity Index was 12. Blood samples of all SLE patients were collected before they received induction therapy. Eight patients were treatment-naïve, while the other patients had treatment with low-dose prednisolone and/or immunosuppressants. Among CD19+ B cells, the proportions of CD38-IgD+ B cells, Bm1 and CD38+IgD+ B cells (Bm2 cells), were lower in SLE patients than in NHCs (p=0.003 and p=0.001). The proportions of CD38++IgD- B cells (Bm3+Bm4 cells) and CD38+CD24- plasmablasts were higher in SLE patients (both p<0.001). Among CD4+ T cells, the proportions of effector memory T cells and HLA-DR+ cells were higher in SLE patients (p<0.001 and p=0.010). Among CXCR5+ Tfh cells, the proportion of CXCR3-CCR6+ Tfh17 cells was lower in SLE patients (p=0.001). In particular, the proportion of CXCR3-CCR6- Tfh2 negatively correlated with the titers of serum complement C3, C4 and white blood cell counts (ρ=-0.66, p=0.021, ρ=-0.77, p=0.003 and ρ=-0.75, p=0.003, respectively), and was higher in SLE patients with skin rash and leukopenia than in patients without them (both p=0.022). The correlations of Tfh2 to clinical parameters were similar to those of plasmablasts but opposite to those of Tfh17. (Fig.1) These results support a report in a lupus model mouse in which Tfh2 contributed to the hypocomplementemia-associated pathogenesis 3).

Conclusion:  Proportions of circulating differentiated B cells and T cells were higher in active SLE patients. Tfh2 and plasmablasts negatively correlated with titers of serum complements and were associated with skin rash and leukopenia. Reference 1) Choi J, et al. Curr Opin Immunol. 2012; 24: 651–7. 2) Le Coz C, et al. PLoS One. 2013. 8: e75319. 3) Futatsugi-Yukimura S, et al. Int Immunol. 2014. 26: 221–31.


Disclosure: J. Kikuchi, None; M. Takeshita, None; K. Suzuki, None; Y. Kassai, Takeda Pharmaceutical Co, Ltd., 3; T. Miyazaki, Takeda Pharmaceutical Co, Ltd., 3; T. Takeuchi, None.

To cite this abstract in AMA style:

Kikuchi J, Takeshita M, Suzuki K, Kassai Y, Miyazaki T, Takeuchi T. Proportions of Circulating Follicular Helper T Cells and Complement Levels, White Blood Cell Counts, and Skin Manifestations in Patients with Active Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/proportions-of-circulating-follicular-helper-t-cells-and-complement-levels-white-blood-cell-counts-and-skin-manifestations-in-patients-with-active-systemic-lupus-erythematosus/. Accessed .
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