Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune disease that can cause systemic organ damage, characterized with the presence of abnormal antibodies (ANCAs) in the circulation and the small- and medium-vessel vasculitis[1].However,the etiology of AAV remained unclear. Several observations have showed that the breakdown of immune tolerance caused by many complex interactions was involved in the pathogenesis of AAV[2].It has been confirmed that the disorder of the CD4+T cell,especially the imbalance of Th17 and Treg cells can destroy the immune tolerance and cause many autoimmune disease[3]. But the relationship between the Th17/Treg and AAV is unknown.Objectives:We investigated the absolute numbers of CD4+T subsets cells in peripheral blood of patients with AAV and healthy adults,and then compared them in different disease activity of AAV to explore the role of CD4+T subsets cells in the pathogenesis and development of AAV.Methods:49 patients with AAV,hospitalized at the Second Hospital of Shanxi Medical University from the May 2016 to the November 2019 were enrolled, and 31 age and gender-matched healthy adults were anticipated as controls.According to BVAS, the patients were divided into disease-activity group (BVAS≥15, n=27) and non-disease-activity group (BVAS<15, n=22). The absolute numbers of CD4+T subsets cells including Th17 and Tregs in peripheral blood of these individuals were detected by flow cytometry.We analyzed whether there was difference of CD4+T subsets between the patients and healthy controls,and between disease-activity group and non-disease-activity group.Results:There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls,especially in the disease-activity group. The absolute numbers of Treg cells was decreased in the patients with AAV compared with healthy controls (P<0.001) leading to a higher Th17/Treg ratio in the patients (P<0.01).Similarly,the absolute number of Treg cells was decreased in the disease- activity group (P<0.01) compared with the non-disease-activity group, and the absolute number of Treg cells was significant negative correlation with the disease activity indexes such as BVAS (r=-0.342,P=0.016), erythrocyte sedimentation rate(ESR) (r=-0.315,P=0.027) and C-reactive protein(CRP) (r=-0.305,P=0.033). But there was no statistically significant in the absolute number of Th17 cells between the patients and healthy controls, and between disease-activity group and non-disease-activity group.Conclusion:The results we investigated here suggested that the decreased number of Treg cells failed to control autoimmune inflammatory response and maintain immune tolerance, and the disease activity of AAV was associated with the reduced number of Treg cells.Figure 1.(A-C) Characteristics of the absolute number of Th17 cells and Treg cells in peripheral blood of healthy controls (n=31) and the patients with AAV (n=49). There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls leading to a higher Th17/Treg ratio in the patients with AAV. (D-F) The absolute number of Treg cells was decreased in the disease- activity group (n=27) compared with the non-disease-activity group (n=21). The absolute number of Th17 cells and Treg cells was detected by flow cytometry. Statistical analyses were performed by the Mann-Whitney U test. *p<0.05,**p<0.01, ***p<0.001.References:[1]Cosmi, L., Th17 and Treg lymphocytes as cellular biomarkers of disease activity in Granulomatosis with Polyangiitis. Eur J Immunol, 2017.47(4): p. 633-636.[2]Pagnoux, C.,Updates in ANCA-associated vasculitis.Eur J Rheumatol, 2016.3: p. 122-133.[3]Diller, M.L., et al., Balancing Inflammation: The Link between Th17 and Regulatory T Cells. Mediators Inflamm, 2016.2016: p. 6309219.Disclosure of Interests:None declared
BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease that results in destruction of joint cartilage and bone. However, many patients do not achieve satisfactory disease control by current therapy with high risk of adverse reactions. We have reported that absolute number of peripheral regulatory T (Treg) cells reduced in RA patients (EULAR Abstract). Moreover, rapamycin has been reported to inhibit differentiation of Th17 and promote growth of FoxP3 +Treg cells by inhibiting mTOR pathway [1].ObjectivesTo observe the therapeutic efficacy of rapamycin on the reduction of disease activity, increase in Tregs and decrease in Th17 to restore balance of Th17/Treg cells in RA patients with high disease activity (DAS28 ≥2.6).MethodsFifty RA patients who treated with two kinds of DMARDs for more than half a year did not achieve remission (DAS28 ≥2.6) were enrolled and were treated with rapamycin at a dose of 0.5 mg every 2 days for 24 weeks. The absolute number of CD4 +T cell subsets in peripheral blood from these patients were assessed by flow cytometry combined with internal standard beads before the treatment as baseline and at week 24 after treatment. Meantime, the DAS28, the dosage of corticosteroids and immunosuppressant were also recorded.ResultsRapamycin treatment reduced the disease activity and induced remission (DAS28<2.6) in 44.9% of active RA patients. Their DAS28 was reduced from a median 2.9 (at week 0) to 1.9 (at week 24) (P<0.001) and the absolute number of peripheral Treg cells was increased from 27.14±15.11 cells/µl (at week 0) to 36.59±17.23 cells/µl (at week 24) (p=0.002). The ratios of Th17/Treg cells also had a significant decrease from 0.36±0.29 at baseline to 0.27±0.20 at week 24 (P<0.041). In contrast, the decrease in the absolute number of Th17 cells was not statistically significant (p=0.846). After the treatment, the proportion of patients taking glucocorticoids decreased from 66.0% to 64.0% and the mean dosage of prednisone decreased from 9.89 mg/d to 7.70 mg/d. And the usages of DMARDs were also reduced (P<0.001).ConclusionsRapamycin combined with low level of conventional therapy effectively reduced disease activity and induced remission among RA patients who received long-term conventional treatment without remission (DAS28 ≥2.6) by increasing the absolute number of Treg cells and restoring the balance of Th17 cells and Treg cells. As the research progresses, rapamycin is likely to become a promising therapeutic candidate.Reference[1] Shan J, Feng L, Sun G, et al. Interplay between mTOR and STAT5 signaling modulates the balance between regulatory and effective T cells. Immunobiology2015;220(4):510–517.Disclosure of InterestNone declared
Background:Secondary Sjogren’s Syndrome (sSS) is diagnosed when symptoms of SS coexist with other systemic connective tissue disease, often secondary to rheumatoid arthritis(RA).The occurrence of SS secondary with RA will worsen the course of disease and increase the high incidence and mortality of RA. At present, the immune characteristics of peripheral blood of sSS with RA are not clear.Objectives:To observe the difference of immune Immune characteristics in peripheral blood between sSS secondary to RA, primary Sjogren’s syndrome(pSS) and RA patients.Methods:20 sSS with RA patients, 20 pSS paients and 20 RA pateints hospitalized in ShanXi medical university the second Hospital were enrolled. The percentage and absolute numbers of lymphocyte phenotypes and CD4+ T subsets in peripheral blood were examined by flow cytometry.Results:As for the percentage and absolute number of total T, B, NK, CD4+T,CD8+ T and the ratio of CD4 + T to CD8+ T cells, there was no significant difference between the sSS with RA, RA, and SS group. There was also no statistical difference in the percentage of CD4+T subsets(Th1,Th2,Th17 and Treg) between the three groups. But the ratio of Th17 and Treg in sSS with RA group was increased than pSS group.About comparison of absolute number of CD4+T subsets, there was no statistical difference among the three groups except that the Th1 cells in RA group was significantly higher than SS group.Conclusion:Elevated Th17/Treg may be an immunological feature that differentiates sSS with RA patients from pSS patients. In addition, in general, peripheral blood of patients with RA and SS have similar immune characteristics.References:[1]Wei W,Ahmad S S, Chi S. From Molecular Mechanism to the Etiology of Sjogren Syndrome.Curr Pharm Des. 2018;24(35):4177-4185.[2]Hajiabbasi A, Masooleh I S,Alizadeh Y, Secondary Sjogren’s Syndrome in 83 Patients With Rheumatoid Arthritis.Acta Med Iran.2016;54(7):448-53.Figure 1.The comparsion about the lymphocyte phenotypes and CD4+ T subsets in peripheral blood of sSS with RA(n=20), pSS(n=20) and RA patients(n=20).(*p<0.05,**p<0.001,*p<0.0001)Disclosure of Interests:None declared
Background:Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disease with chronic systemic inflammation and fibrosis. The main feature of the disease was diffuse swell of the affected organs, and the serum IgG4 level was increased. Histopathology of the lesions showed infiltration of IgG4+ plasma cells. However, the pathogenesis of IgG4-RD is still unclear[1].Objectives:To explore the clinical characteristic of lymphocyte subsets of IgG4-related disease patients, and make comparisons with healthy controls.Methods:A total of 31 patients with IgG4-RD who were admitted to the Rheumatic Immunology Department of the Second Hospital of Shanxi Medical University from January 2016 to June 2020 were included. We collected their Clinical and laboratory data, and selected 30 age and sex matched healthy people as the control group. Flow cytometry was used to detect the percentage and absolute number of lymphocyte subsets (T, B, NK, CD4+T, CD8+T) and CD4+T subsets (Th1, Th2, Th17, CD4+CD25+Foxp3+Treg) in peripheral blood of IgG4-RD patients and healthy controls.Results:(1)The percentage of CD4+T cells in peripheral blood of IgG4-RD patients was higher than that of healthy controls [45.00(33.97-51.48) vs. 39.36(33.78-43.30), P<0.05]. (2)The percentage and absolute number of Th17 cells was increased in IgG4-RD patients [1.13(0.70-1.55) vs. 0.77(0.43-1.07), P<0.05; 7.90(5.20-12.23) vs. 5.60(3.12-8.47), P<0.05], while the percentage of Treg cells was decreased [3.37(2.82-5.65) vs. 4.96(4.18-6.34), P<0.01]. But Treg cells number showed no difference between the two groups. (3) Th17/Treg ratio was significantly increased in IgG4-RD patients [0.29(0.16-0.46) vs. 0.15(0.08-0.23), P<0.01], and it was positively correlated with IgG4-RD response index score(r=0.491, P<0.01). (Table 1).Table 1.Comparation of absolute number and percentage of peripheral blood lymphocyte subsets between IgG4-RD patients(n=31) and healthy controls (n=30).cell subsetsIgG4-RD (n=31)HC(n=30)P valueB150.59(120.14-212.38)203.27(152.90-244.27)0.089B%8.74(6.46-11.45)10.03(8.26-13.21)0.059NK261.98(178.82-303.08)290.83(179.93-451.45)0.175NK%13.14(9.92-18.10)16.50(11.24-21.75)0.105CD3+T1357.44(992.00-1844.82)1305.81(978.24-1597.94)0.708 CD3+T%72.62(69.32-76.96)71.62(64.97-75.25)0.135CD8+T436.40(342.71-596.86)513.50(359.73-620.53)0.665CD8+T%24.26(19.48-31.27)26.50(20.67-32.90)0.535CD4+T741.00(562.78-1095.52)664.50(585.52-789.97)0.428CD4+T%45.00(33.97-51.48)39.36(33.78-43.30)0.032Th1162.32(108.11-216.61)144.27(81.52-161.66)0.094Th1%19.00(15.24-25.54)18.46(14.86-24.27)0.644Th27.82(5.35-11.78)8.25(5.32-10.87)0.817Th2%1.00(0.76-1.27)1.24(0.89-1.64)0.399Th177.90(5.20-12.23)5.60(3.12-8.47)0.010Th17%1.13(0.70-1.55)0.77(0.43-1.07)0.026Treg24.45(19.76-44.79)34.55(27.29-46.57)0.076Treg%3.37(2.82-5.65)4.96(4.18-6.34)0.003Th1/Th220.00(13.78-36.36)14.97(10.31-21.58)0.135Th1/Treg5.72(2.92-8.86)3.68(2.53-4.77)0.021Th2/Treg0.27(0.16-0.52)0.22(0.15-0.32)0.199Th17/Treg0.29(0.16-0.46)0.15(0.08-0.23)0.002Conclusion:Th17/Treg immune disorder exists in IgG4-RD patients, and it is related to the disease activity, indicating that Th17/Treg imbalance may be an important pathogenesis of IgG4-RD.References:[1]Kamisawa T, Zen Y, Pillai S, et al. IgG4-related disease[J]. Lancet, 2015, 385(9976): 1460-1471.Disclosure of Interests:None declared
Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune disease that can cause systemic organ damage, including granulomatosis with polyangiitis(GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis(EGPA)[1]. Several observations have showed that the breakdown of immune tolerance was involved in the pathogenesis of AAV [2], furthermore, a single, open and clinical trial demonstrates that IL-2 can be used to treat patients with GPA [3]. But there is still a lack of understanding of the relationship between Th17 / Treg and AAV and evidence for the therapeutic effect of IL-2 on AAV, which needs further exploration.Objectives:We first measured the absolute number of CD4+T subsets in peripheral blood of patients to explore the pathogenesis of AAV, and then investigated the effects of short-term and low-dose recombinant human IL-2 (rhIL-2) on CD4+T subsets of patients to analyze the regulatory effect of IL-2 on AAV.Methods:49 patients with AAV, hospitalized at the Second Hospital of Shanxi Medical University from the May 2016 to the November 2019 were enrolled, including 36 patients who were only received conventional glucocorticoids and DMARDs, and other 13 patients who were not only received these treatments but were also injected subcutaneously rhIL-2(50WIU/day for a 5-day course). 31 age and gender-matched healthy adults were selected as controls. The absolute number of Th17 and Treg cells in peripheral blood of health controls and the patients before and after treatment was detected by flow cytometry.Results:There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls (P<0.001) leading to a higher Th17/Treg ratio in the patients with AAV, but there was no statistically significant in the absolute number of Th17 cells between the patients and healthy controls. After the treatment of short-term and low-dose IL-2, there was a significant increase in the absolute number of Treg cells (P<0.01) leading to a decrease in the ratio of Th17 and Treg (p<0.05).The absolute number of Th17 had a trend towards higher values but was not statistical significance.Conclusion:The difference of Treg cells between the patients and healthy controls suggested that the decreased number of Treg cells failed to control autoimmune inflammatory response contributing to the pathogenesis of AAV. After the treatment of short-term and low-dose rhIL-2, there was a more significant increase in the absolute number of Treg cells showing that IL-2 could selectively stimulate the growth of Treg cells and restore the Treg-mediated immune tolerance in patients with AAV to achieve disease remission.References:[1]Cosmi, L.,Th17 and Treg lymphocytes as cellular biomarkers of disease activity in Granulomatosis with Polyangiitis.Eur J Immunol, 2017.47(4): p. 633-636.[2]Pagnoux, C.,Updates in ANCA-associated vasculitis.Eur J Rheumatol, 2016.3: p. 122-133.[3]Rosenzwajg, M., et al.,Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial.Annals of the Rheumatic Diseases, 2019.78(2): p. 209-217.Disclosure of Interests:None declared
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