| Objective:To compare the absolute counting of lymphocyte subtypes of healthy control and that of patients with refractory rheumatoid arthritis(RRA);to explore the effect of DMARDS and low-dose IL-2 on the absolute counting of these lymphocyte subtypes;to evaluate clinical efficacy and safety of low dose IL-2 in patients with RRA.Methods:Patients with RRA(n = 41)and healthy controls(n = 40)were included in our study.Absolute number of lymphocyte subsets in peripheral blood mononuclear cells(PBMC)from these participations were characterized by multicolor flow cytometry(FCM).The patients were divided randomly into two groups: Non-IL-2 group(n=15)who were still given conventional glucocorticoids and DMARDs treatment and IL-2 group(n=26)who were not only given same conventional treatment but also injected subcutaneously IL-2at 0.5 million IU per day for 5 consecutive days.Before and after the treatment,peripheral lymphocyte subpopulation and the CD4+T subgroups of the patients were measured by FCM.The absolute number of those cells were compared between Non-IL-2 and IL-2 groups as well as between before and after treatment.The disease activity measures such as the 28-joint Disease Activity Score,tender joint count(TJC),swollen joint count(SJC),erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)were recorded and compared between Non-IL-2 and IL-2 groups.The incidence and severity of all adverse events were recorded.The blood routine,Liver andrenal function were detected before and after the treatment.Results:No significant difference observed in age(55.1±13.83 vs.50.9±9.495)and sex(female percentage 68.3% vs.67.5%)compared between RA patients and health donors(P > 0.05).The absolute counting of B cells,NK cells and Treg cells were significantly lower in RRA patients compared with that in health donors(P < 0.05),the ratio of Th17 and Tregs was significantly higher in patients compared with that in health controls(P < 0.01).Before IL-2 treatment,there were no significant differences in the numbers of CD4+T cell subsets between IL-2 group and non-IL-2 group(P > 0.05).After IL-2treatment,compared with before-treatment as well as with non-IL-2 control,there was a significant increase in T cells [990(799,1301)vs.1227(954,2026),P = 0.015],B cells[144(80,213)vs.218(149,445),P = 0.005] and CD4+T cells [564(417,832)vs.823(597,1334),P = 0.003].There was also an increase in Th17 cells [9(4,16)vs.17(9,29),P = 0.008] and Treg cells [23(14,30)vs.65(48,102),P < 0.001].However,it is noteworthy that the Treg cells were increased much more dramatically than the Th17 cells,leading to a decrease in their ratio [0.40(0.23,0.76)vs.0.23(0.12,0.44),P =0.010].Before the treatment,there was no difference in disease activity measures between IL-2 group and Non-IL-2 group(P > 0.05).But after IL-2 subcutaneous injection combined with same conventional antirheumatic drugs,there was a significant decrease in DAS28 score(3.60 ± 0.96 vs.2.85 ± 0.67,P = 0.005),28 tender joint count(3.73 ±2.79 vs.0.94 ± 1.00,P = 0.001)and swollen joint count(1.40 ± 1.64 vs.0.42 ± 0.70,P =0.011)in IL-2 group,compared with non-IL-2 treatment individuals.There were no differences in blood routine,serum Alanine transaminase(ALT),aspartate aminortransferase(AST),Blood urea nitrogen(BUN),serum creatinine(Scr)between two groups before the treatment(P > 0.05).After the treatment,thesemeasurements were also comparable in these two groups(P > 0.05)).Except for mild reactions at the site of injection in some subjects(2 of 26 patients)there were no other side effects observed.Conclusion:Patients with RRA had an autoimmune disorder by abnormalities the peripheral lymphocyte subsets,especially the absolute decrease of Treg cells.Low-dose IL-2,a potential therapeutic candidate,restored decreased Treg cells and promoted rapidly remission of patients with RRA without over-treatment and evaluated side effects. |
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