Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus

Abstract

Objective Juvenile-onset systemic lupus erythematosus (JSLE) is a complex and heterogeneous immune-mediated disease. Cellular components have crucial roles in disease phenotypes and outcomes. We aimed to determine the associations of lymphocyte subsets with clinical manifestations and long-term outcomes in JSLE patients. Methods A cohort of 60 JSLE patients provided blood samples during active disease, of whom 34 provided further samples during inactive disease. In a longitudinal study, blood samples were obtained from 49 of the JSLE patients at 0, 3, and 6 months. The healthy control (HC) group consisted of 42 age-matched children. Lymphocyte subsets were analyzed by flow cytometry. Results The percentages of CD4+ T, γδ T, and NK cells were significantly decreased in JSLE patients compared with HC, while the percentages of CD8+ T, NKT, and CD19+ B cells were significantly increased. The percentage of regulatory T cells (Tregs) was significantly lower in JSLE patients with lupus nephritis (LN) than in non-LN JSLE patients and HC. The patients were stratified into high and low groups by the median frequency of each lymphocyte subset. The γδ T cells high group and NK cells high group were significantly related to mucosal ulcer. The CD4+ T cells high group was significantly associated with arthritis, and the NKT cells high group was substantially linked with autoimmune hemolytic anemia. The CD8+ T cells low group was mainly related to vasculitis, and the Tregs low group was significantly associated with LN. The percentage of Tregs was significantly increased at 6 months of follow-up, and the LN JSLE group had a lower Treg percentage than the non-LN JSLE group. Predictors of remission on therapy were high Tregs, high absolute lymphocyte count, direct Coombs test positivity, and LN absence at enrollment. Conclusion JSLE patients exhibited altered lymphocyte subsets, which were strongly associated with clinical phenotypes and long-term outcomes.

CD8+ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease

“…Two studies involving 60 or more JSLE patients reported an increase in total CD8 + T cell frequency in JSLE compared to HC [ 92 , 93 ], one of which, also reported reduced frequencies of CM, EM, and TEMRA CD8 + T cells in peripheral blood of patients with JSLE [ 93 ]. Lerkvaleekul et al found the increase in total CD8 + T cell frequency in JSLE to be associated with mild disease and absence of vasculitis and LN [ 92 ].…”

“…Two studies involving 60 or more JSLE patients reported an increase in total CD8 + T cell frequency in JSLE compared to HC [ 92 , 93 ], one of which, also reported reduced frequencies of CM, EM, and TEMRA CD8 + T cells in peripheral blood of patients with JSLE [ 93 ]. Lerkvaleekul et al found the increase in total CD8 + T cell frequency in JSLE to be associated with mild disease and absence of vasculitis and LN [ 92 ]. Robinson et al, on the other hand, reported that JSLE patients with elevated CD8 + EM cells had higher disease activity over time, increased use of mycophenolate mofetil (MMF), and increased prevalence of LN, highlighting a possible role for these cells in the pathology of more severe JSLE [ 93 ].…”

“…Our literature search identified only 8 studies focused on CD8 + T cell peripheral blood profiles in juvenile CTDs (5 in JSLE and 3 in JDM). Much like in adult disease, in JSLE CD8 + T cell frequencies were either reported as increased or unchanged while absolute cell counts were decreased [ 92 , 93 , 94 , 95 ]. In JDM total CD8 + T cell frequencies or absolute counts were reduced compared to HC across all studies [ 90 , 97 , 98 ].…”

Is There a Link between the Molecular Basis of Juvenile Idiopathic Arthritis and Autoimmune Diseases? Systematic Review

“…Lerkvaleekul et al [ 36 ] analysed differences in lymphocyte subpopulations in SLE and their long-term outcomes, discovering that elevated CD4+ levels increased the likelihood of developing arthritis. An imbalance of lymphocyte subtypes altered the immune response in SLE patients, triggering an inflammatory response.…”

Association of regulatory T cells with renal outcomes in patients with proliferative lupus nephritis

“…A previous study showed that the number of Tregs in LN patients increased significantly after 6 months of immunosuppression treatment. 22 However, cyclophosphamide treatment completely suppressed Tregs proliferation in the spleen, lymph nodes, thymus, and peripheral blood, resulting in a drop in Tregs absolute numbers. 23 Another study showed that the percentage of Tregs in SLE patients decreased under immunosuppressive therapy.…”