Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Circulating T Helper Cells in Patients with Systemic Lupus Erythematosus Share the Phenotypic Property with Lymphoid T Follicular Helper Cells.
Lindwall1, Elvira, Gauthier1, Carl, Alarakhia1, Anika, Menga1, Gwendoline, Zakem1, Jerald M., Davis1, William E., Webb-Detiege1, Tamika A.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoreactive B cells and autoantibody (autoAb) production. These autoAbs bind to self-antigens, leading to multisystem disease. T follicular helper (TFH) cells, a T cell subset located in germinal center in secondary lymphoid organs, have emerged as a key participant that controls B cell peripheral tolerance and Ab production. Previously we have found that circulating TFH (cTFH) cells are expanded in SLE patients. To identify the origin and the role of cTFH cells in SLE, we compared the phenotypic property of cTFH cells in SLE patients with lymphoid TFH cells in the secondary lymphoid organ (tonsil), and correlated the percentage of cTFH cells with autoAb production and disease activity in SLE patients.
Eighteen SLE patients diagnosed according to the ACR criteria were recruited. The disease activity was determined by SLEDAI. Blood from these lupus patients and eighteen age, gender-matched healthy controls was obtained. Mononuclear cells were isolated by Ficoll density-gradient centrifuge, and stained with fluorescent-conjugated Abs. TFH cells were defined by their signature surface markers (CD4+CXCR5+ICOS+CD57+) via flow cytometry and analyzed using FlowJo software. The cTFH cells, non- cTFH cells from SLE patients, and lymphoid TFH cells from tonsils were purified by MACS columns, and the purities were above 90%. The expression levels of cytokines of these cells were measured by RT-PCR and intracellular staining. Plasmablasts were identified by surface CD20loCD38hiexpression. Levels of anti-dsDNA Ab, anti-nuclear Ab (ANA), C3 and C4 were also collected. Statistical analysis was carried out using GraphPad Prism software and the significance was evaluated by t test. Correlation analysis was determined by Spearman's rank correlation test as r value.
The frequency of cTFH cells was significantly increased in SLE patients compared to healthy controls (P<0.01). This elevated frequency of cTFH cells had a positive correlation with levels of circulating plasmablasts, serum anti-dsDNA Ab and ANA, but no correlation with serum C3 and C4. In addition, cTFH cells from SLE patients shared similar phenotype and frequency with lymphoid TFH cells, with less intense expression of co-stimulatory molecules CXCR5, CD57, and ICOS. Both the cTFH cells from SLE patient and lymphoid TFH cells expressed significant higher amounts of IL-21, IL-6 and IL-10 than non-TFH cells in lupus patients and T helper cells from healthy donors. These cytokines are known to drive B cells to differentiate into IgG-secreting plasma cells in vitro.
The increased frequency of ectopically located cTFH cells in SLE patients share a similar phenotype with lymphoid TFH, and may derive from lymphoid organs. By secreting plasma cell driving cytokines (IL-21, IL-10, and IL-6), these accumulated cTFH cells may ensure that self-reactive B cell clones further differentiate to plasmablasts producing autoAbs in the periphery, thus serve as perpetrators in the pathogenesis in SLE patients and a possible mechanism for treatment.
To cite this abstract, please use the following information:
Lindwall, Elvira, Gauthier, Carl, Alarakhia, Anika, Menga, Gwendoline, Zakem, Jerald M., Davis, William E., et al; Circulating T Helper Cells in Patients with Systemic Lupus Erythematosus Share the Phenotypic Property with Lymphoid T Follicular Helper Cells. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :646