Reduced numbers of regulatory B cells are negatively correlated with disease activity in patients with new-onset rheumatoid arthritis.
This study is aimed at determining the numbers of circulating Treg and Breg cells in patients with new-onset rheumatoid arthritis and during subsequent drug therapies. Patients were treated orally with 10 mg methotrexate weekly, and 20 mg leflunomide and 60 mg common threewingnut root daily (Lei Gong Teng) for 12 weeks, but received no steroid therapy. Basal measurements were performed of serum C-reactive protein, anticyclic citrullinated peptide antibody, and erythrocyte sedimentation rate, and the numbers of cluster of differentiation CD4(+)CD25(+)Foxp3(+) T cells, interleukin 10 (IL10)-expressing on CD5(+)CD1d(+) and TIM1(+) B cells. Compared with the healthy controls, patients exhibited significantly less numbers of circulating CD19(+)TIM1(+)IL10(+), CD19(+)CD5(+)CD1d(+)IL10(+) B cells and CD4(+)CD25(+)Foxp3(+) T cells (P < 0.001, all). Drug therapy modulated the balance of different subsets of Breg and Treg cells. The numbers of CD19(+)TIM1(+)IL10(+) and CD19(+)CD5(+)CD1d(+)IL10(+) B cells correlated positively with the numbers of CD4(+)CD25(+)Foxp3(+) T cells in these patients (r = 0.707, P = 0.001; r = 0.481, P = 0.007, respectively). The values of DAS28 were negatively correlated with the numbers of CD19(+)TIM1(+)IL10(+) and CD19(+)CD5(+)CD1d(+)IL10(+) B cells, and CD4(+)CD25(+)Foxp3(+) T cells (r = -0.533, P = 0.023; r = -0.442, P = 0.016; and r = -0.444, P = 0.014, respectively). Of note, TIM1(+) B cells identified more circulating IL10(+) B cells than CD5(+)CD1d(+) B cells. Our data indicate that Breg and Treg cells have a potentially crucial role in controlling disease activity in rheumatoid arthritis patients, and TIM1(+) Breg cells may be a viable therapeutic target for these patients.
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Changchun, 130032, China, maliang212@126.com.
Liang
L
Ma
Bin
B
Liu
Zhenyu
Z
Jiang
Yanfang
Y
Jiang
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D055610:Antigens, CD1d / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000166:cytology*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007555:Isoxazoles / Q000008:administration & dosage; D000077339:Leflunomide; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010936:Plant Extracts / Q000008:administration & dosage; D011991:Receptors, Virus / Q000378:metabolism
D000906:Antibodies; D055610:Antigens, CD1d; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C508609:IL10 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D007555:Isoxazoles; D008562:Membrane Glycoproteins; D010456:Peptides, Cyclic; D010936:Plant Extracts; D011991:Receptors, Virus; C487763:cyclic citrullinated peptide; C041579:lei gong teng; D016753:Interleukin-10; D002097:C-Reactive Protein; D000077339:Leflunomide; D008727:Methotrexate