Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
It is increasingly appreciated that circulating B cells are functionally altered and are involved in pathogenic process in patients with systemic lupus erythematosus (SLE). We previously reported that anti-dsDNA antibody-secreting B cells and plasma cells were recruited into circulation in active disease phase in SLE patients. In this study, we evaluated roles of circulating B cells in pathogenic process of SLE by focusing on chemokines.
Methods
We studied peripheral blood samples from 38 patients with SLE and 13 healthy donors. We recorded the disease activity index (SLEDAI) at blood sampling by a retrospective chart review. According to the previous report, active disease was defined as SLEDAI ≥ 5. Peripheral blood mononuclear cells (PBMCs) were obtained by density gradient centrifugation and analyzed by flow cytometry for expression or mean fluorescence intensity of CXCR4, CXCR5 and CCR7 on CD19+ B cells. The concentration of serum CXCL12, which is a ligand for CXCR4, was also measured by enzyme immunoassay. Chemotaxis assay was conducted to test the chemotactic responsiveness of B cells toward the CXCL12. Infiltration of CD19+ B cells with expression of CXCR4 in renal tissue from patients with lupus nephritis ISN/RPS class IV was semi-quantitatively assessed by immunohistochemistry. In this experiment, renal specimens from patients with IgA nephropathy were used as a disease control.
Results
Seventeen active and 21 inactive patients with SLE were enrolled. Flow cytometric analysis revealed that expression of CXCR4 was higher in patients with SLE than normal healthy controls (p = 0.035). In patients with SLE, the expression of CXCR4 was higher in those with active disease than in those with inactive (p = 0.001). The expression levels of CXCR5 and CXCR7 were not different between patients with SLE and normal healthy controls. In contrast, there was no difference in circulating concentration of CXCL12 between patients with active and inactive disease (2113 vs 2201 pg/ml, p = 0.263). Migration ability of B cells toward CXCL12 was enhanced in SLE patients compared with normal healthy controls (33.9 vs 19.4 %, p = 0.005). Moreover, SLE patients with active disease represented more prominent chemotaxis towards CXCL12 than did those with inactive disease (52.9 vs 27.6 %, p = 0.004). Finally, infiltration of CXCR4-expressing CD19+ B cells into the renal interstitium was more prominent in lupus nephritis than IgA nephropathy (p = 0.003).
Conclusion
In SLE patients with active disease, B cells with up-regulated expression of CXCR4 and enhanced chemotaxic responsiveness towards CXCL12 were increased in circulation. These aberrant B cells may be involved in the pathogenic process of SLE by infiltrating into the inflamed organs such as kidneys.
Disclosure:
H. Hanaoka,
None;
Y. Okazaki,
None;
A. Hashiguchi,
None;
H. Yasuoka,
None;
T. Takeuchi,
Abbott Japan Co., Ltd., Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Sanofi–Aventis K.K., Santen Pharmaceutica,
2,
Abbott Japan Co., Ltd., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Diaichi Sankyo Co.,Ltd.,
8,
Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., Abbivie GK, Daiichi Sankyo Co.,Ltd.,
5;
M. Kuwana,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/up-regulated-expression-of-cxcr4-on-circulating-b-cells-in-patients-with-systemic-lupus-erythematosus/