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Background:Increased serum autoantibodies against interleukin-2 (anti-IL-2 autoantibodies) were reported in patients with systemic lupus erythematosus (SLE) and in patients receiving IL-2 therapy.This study aimed to explore the clinical relevance of serum anti-IL-2 autoantibodies and the interactions between low-dose IL-2 therapy and serum anti-IL-2 autoantibodies.Methods:Serum samples were collected from 152 SLE patients and 100 age-and gender-matched healthy controls (HCs).Among them,75 SLE patients were followed up for 10 weeks,and all of them were treated with corticosteroids,antimalarials,and/or immunosuppressants.Forty-six out of the 75 SLE patients received low-dose IL-2 therapy additionally.Clinical and laboratory parameters were collected at baseline and week 10.Serum anti-IL-2 autoantibodies were determined by enzyme-linked immunosorbent assay.Results:Compared with HCs,median levels and positive rates of serum anti-IL-2 autoantibodies were higher in SLE patients (32.58 [23.63,45.23] arbitrary unit [AU] vs.37.54 [27.88,60.74] AU,P =0.006,and 5.0％ vs.18.4％,P =0.002,respectively).Compared to those without the corresponding disorders,serum anti-IL-2 autoantibody was increased in patients with alopecia (49.79 [36.06,64.95] AU vs.35.06 [25.40,58.46] AU,P =0.033),but it was decreased in those with lupus nephritis (31.71 [22.60,43.25] AU vs.44.15 [31.43,68.52] AU,P =0.001).Moreover,serum anti-IL-2 autoantibody was positively correlated with serum IgA (r =0.229,P =0.005),total IgG (r =0.327,P ＜ 0.00 1),and total IgM (r 0.164,P =0.050).Treatment with exogenous IL-2 was not significantly associated with serum anti-IL-2 autoantibody.In addition,no significant difference was found in serum anti-IL-2 autoantibody between responders and nonresponders to low-dose IL-2 therapy.Conclusions:Serum anti-IL-2 autoantibody was increased and associated with disease severity in SLE.Exogenous low-dose IL-2 did not significantly induce anti-IL-2 autoantibody production.