Background/Purpose:  Peripheral CD4+CD28null T-cells constitute a subset of long-lived cytotoxic CD4+ T-cell with pro-inflammatory functions. This T-cell subpopulation has been reported to be associated with damage in SLE patients, but whether it may be predictive of such occurrence has not previously been reported. The aim of this study was to determine whether this T-cell subset predicts the occurrence of new damage in these patients.

Methods:  This longitudinal study was conducted in consecutive SLE patients seen every six months in our Rheumatology Department since 2013. For the purpose of this study, patients in whom CD4+CD28null T-cells had been measured and who had at least one subsequent visit thereafter were included. Variables were evaluated during the same visit in which CD4+CD28null cells were measured (interview, medical records review, physical examination and laboratory tests) with the exception of damage which was evaluated in the subsequent visits. SLE was defined by the 1997 revised and updated ACR criteria. Disease activity was ascertained using the SLEDAI and disease damage with the SLICC/ACR damage index (SDI). Use of prednisone was recorded as current dose and total time of exposure. Use of antimalarials and immunosuppressives was recorded as current, past or never. CD4+CD28null T-cells frequencies were analyzed by flow-cytometry. Survival analyses using univariable and multivariable Cox-regression models were performed to determine the risk of overall damage and per each SDI domain individually as a function of the frequency of this T-cell subpopulation. The multivariable model was adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, use of prednisone, antimalarials and immunosuppressive drugs at the intake visit. All analyses were performed using SPSS 21.0.

Results:  One hundred and nineteen patients were evaluated; their mean (SD) age was 43.5 (11.9) years, 113 (95.0%) were female; all patients were Mestizo (mixed Caucasian and Amerindian ancestry). Socioeconomic level was low in 50 (42.0%), medium in 48 (40.3%) and high in 21 (17.6%) patients. Disease duration was 7.8 (7.0) years. The SLEDAI was 5.3 (4.1) and the SDI 1.0 (1.4). At baseline, the dose of prednisone was 6.9 (5.1) mg/day and the total time of exposure to prednisone was 7.3 (6.8) years; 93 (78.2%) and 13 (10.9%) patients were current and former users of antimalarials. Fifty-six (47.1%) and 28 (23.5%) patients were current and former users of immunosuppressive drugs. The percentage of CD4+CD28null T-cells was 17.4 (14.0). Forty-six (38.7%) patients increase at least one point in the SDI. In the univariable and multivariable analyses, the percentage of CD4+CD28null predicted the occurrence of lung damage [HR: 1.042 (CI95%: 1.001-1.085); p=0.047 and HR: 1.099 (CI95%1.020-1.184); p=0.013, respectively] but neither the total SDI score nor all other SDI domain scores were predicted by the percentage of CD4+CD28null cells.

Conclusion:  In SLE patients, CD4+CD28null T-cells predict the occurrence of new lung damage, independently of other risk factors.

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-cd4cd28null-t-cells-predict-the-occurrence-of-new-lung-damage-in-systemic-lupus-erythematosus-sle-patients/