| Background:Systemic lupus erythematosus(SLE)is an autoimmune disease involving multiple organs,multisystems with the appearance of several autoantibodies,and the underlying pathological change is immune complex mediated vasculitis,characterized by the breakdown of immune tolerance,leading to autoimmune reactions and corresponding tissue and organ damage.The imbalance between T helper 17(Th 17)and regulatory T cells(Treg)is one of the bases of the pathogenesis of SLE.Th 17 cells have a proinflammatory role,whereas Treg have immunosuppressive functions and play an important role in the induction and maintenance of self tolerance.The decrease and dysfunction of Treg content are closely related to the occurrence and development of SLE.Therefore,regulating the Th 17/Treg balance becomes a new direction for the treatment of SLE.Studies have shown that low-dose interleukin-2(IL-2)therapy can selectively promote Treg cells and suppress Th 17 cells and follicular helper T cells(Tfh),while it can significantly reduce disease activity in SLE patients.In clinical practice,abnormal hematological parameters are the most common manifestation in SLE patients,with the incidence of lymphopenia being second only to anemia,and lymphopenia is an important immune subtype of SLE,so to explore the effect of lymphopenia on the balance of Th 17/Treg in SLE patients,and whether low-dose IL-2 treatment can regulate the Th 1 7/Treg balance,thereby controlling disease progression and maintaining disease stability,can provide new ideas for the treatment of SLE with lymphopenia.Objective:1.To investigate whether there are differences in Tfh cells as well as the typing of Treg cells between SLE patients with lymphopenia and those with normal lymphocytes,and their correlation with absolute lymphocyte values,thereby demonstrating the impact of lymphopenia on immune function in SLE patients.2.To explore whether there are differences in the absolute Th 17 and Treg cell counts,Th 17/Treg balance,and related cytokines between SLE patients with lymphopenia and normal lymphocytes,and whether low-dose IL-2 treatment can modulate the Th 17/Tregbalance,thereby controlling disease progression and maintaining disease stability,and to provide new insights into the treatment of SLE with lymphopenia.Methods:A total of 70 patients with SLE who were recruited from the rheumatology clinic of The Second Hospital of Shanxi Medical University from September 2022 to March 2023were divided into low lymphocyte(n=3 8)and normal lymphocyte(n=32)groups according to whether the absolute value of lymphocytes was lower than 1.5×10~9/L.The percentages and absolute counts of each subtype of Tfh and Treg cells were compared between the two groups,and the percentages and absolute counts of each subtype of Tfh and Treg cells were compared between the two groups to investigate whether the absolute counts of Tfh and Treg cells were correlated with the absolute numbers of lymphocytes.A total of 131 SLE patients who were hospitalized in the rheumatology department of The Second Hospital of Shanxi Medical University from September 2018 to September 2021 were selected and divided into a low lymphocyte group(n=96)and a normal lymphocyte group(n=35)based on whether the absolute value of peripheral lymphocytes was lower than 1.5×10~9/L,while the other 30 healthy controls were selected.The clinical characteristics,laboratory tests and other data of the patients were collected.The absolute number and percentage of peripheral blood lymphocyte subpopulations and CD4~+T cell subpopulations in the lymphopenic group,the normal lymphocyte group,and the healthy control group were detected by flow cytometry,and the serum cytokine level was detected by flow cytometry bead array(CBA).Compare the differences among peripheral blood lymphocyte subsets,CD4~+T subsets,and cytokines in each group.Patients were divided into low-dose IL-2 treatment group(30 cases)and non low-dose IL-2 treatment group(101 cases)based on whether they received low-dose IL-2treatment.The above indicators were measured before and after treatment in the two groups,and the differences were analyzed.The Spearman correlation coefficient was used to analyze the correlation between the absolute counts of Th 17,Treg,and the ratio of Th 17/Treg with the absolute values of lymphocytes and cytokines.Results:1.The absolute counts of Tfh,Treg,n Treg,and i Treg cells in the lymphopenia group were significantly lower than those in the normal lymphocyte group(P values were<0.001,<0.001,<0.001,and 0.003,respectively).There was no statistically significant difference in the overall distribution of Treg(%),n Treg(%),i Treg(%),and Tfh cells(%)between the lymphocytopenia group and the normal lymphocyte group(P=0.976,0.289,0.263,and 0.659,respectively).The absolute value of lymphocytes was positively correlated with the absolute counts of Tfh,Treg,n Treg,and i Treg cells(r=0.603,0.594,0.467,and 0.472,respectively,P<0.001).2.The C-reactive protein,erythrocyte sedimentation rate,and anti ds DNA values of SLE patients with lymphopenia were higher than those of SLE patients with normal lymphocytes(P<0.001),while the leukocyte count and complement C3 were lower than those of SLE patients with normal lymphocytes(P<0.001,0.0037,respectively),while the difference in complement C4 was not statistically significant(P=0.465).3.The absolute value of Treg cells in peripheral blood of SLE patients with lymphopenia was lower than that of healthy controls and SLE patients with normal lymphocytes(P<0.001);in patients with normal lymphocytes,only the absolute value of Treg cells in peripheral blood decreased compared to healthy controls(P=0.005).There was no significant difference in the absolute value of peripheral blood Th 17 cells between patients with lymphopenia and healthy controls(P=0.272),but the absolute value of peripheral blood Th 1 7 cells in patients with normal lymphocytes was higher than those in patients with lymphopenia and healthy controls(P<0.001).The Th 17/Treg ratio of patients in both groups was higher than that of healthy controls(P<0.001),but there was no statistically significant difference between the two groups.The concentration of cytokines in both groups of patients,except IL-2,was higher than that in healthy controls(P<0.001),while there was no statistically significant difference between the two groups of patients(P=0.542,0.940,0.053,0.337,0.770,respectively).4.In SLE patients with lymphopenia who received low-dose IL-2 treatment,the SLEDAI score decreased compared to the previous treatment(P<0.001),the white blood cell count and the absolute value of lymphocytes increased(P<0.001),anti ds DNA decreased compared to the previous treatment,and hypocomplementaemia improved(P<0.008,<0.001,respectively).After treatment,the absolute values of total T lymphocytes,Th 1 cells,Th2 cells,Th 17 cells,and Treg cells in patients increased(P values were 0.001,0.005,<0.001,0.026,and 0.021,respectively),although there was no significant difference before and after the Th 17/Treg ratio(P=0.819).In patients with SLE who did not receive low-dose IL-2 treatment,their SLEDAI score and erythrocyte sedimentation rate decreased compared to before(P<0.001),their white blood cell count and lymphocyte absolute value also increased(P<0.002 and 0.001,respectively),their anti ds DNA decreased compared to before treatment,and their hypocomplementaemia improved(P<0.001);however,the improvement in immune function was not significant,with only an increase in total T lymphocytes,NK cells,and Th2 cells(P values were0.037,0.006,and 0.021,respectively).There was no statistical difference in the absolute values of total B lymphocytes,Th cells,Th 1 cells,Th 17 cells,Treg cells,and the Th 17/Treg ratio before and after treatment(P values were 0.122,0.176,0.122,0.624,0.343,and 0.206,respectively).5.The absolute counts of Th 17 and Treg were positively correlated with the absolute values of lymphocytes(r=0.640,0.619,P<0.001),but the correlation between the Th 17/Treg ratio and the absolute values of lymphocytes was not significant(r=0.122,P=0.169).The Th 17/Treg ratio was negatively correlated with IL-2 concentration(r=-0.292,P=0.003).Conclusion1.Treg cell typing and the absolute Tfh cell count are lower in the peripheral blood of SLE patients with lymphopenia than in SLE patients with normal lymphocytes and correlate positively with the absolute lymphocyte count2.SLE patients have Th 17/Treg imbalance and increased secretion of related cytokines,and SLE patients with reduced lymphocytes have more severe Th 17/Treg imbalance.3.Low dose IL-2 treatment can improve Th 17/Treg imbalance in SLE patients with reduced lymphocytes. |
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