| BACKGROUND ANCA associated vasculitis(Antineutrophil cytoplasmic autoantibody associated vasculitis,AAV)was a kind of autoimmune vasculitis involving almost all the small blood vessels,and it included Microscopic polyangiitis(MPA),Granulomatosis with polyangiitis(GPA)and Eosinophilic Granulomatosis with polyangiitis(EGPA).ANCA was the serological hallmarker of these diseases and the main specific antigens of ANCA included myeloperoxidase(MPO)and protease-3(PR-3).Unlike that in Europe or the United States,MPO-AAV was more common than PR3-AAV in our country.Because of hiding onset,rapid progression,widely affected organs and the high mortality of the disease,the research on the pathogenesis of AAV was necessary.The exact pathogenesis of MPO-AAV remained unclear,studies had found that MPO-ANCA might play a key role in this desease.MPO ANCA,as a kind of autoantibody,was produced by plasma cells,which was regulated by many mechanisms of the immune system.In recent years,a new type of T cell subgroup positioning in lymphoid follicles,named Follicular helper T cells(Tfh),came to be known.The cell specifically expressed CXC chemokine receptor 5(CXCR5),inducible stimulating molecules(ICOS),programmed cell death protein 1(PD-1),and etc.and it also secreted interleukin – 21(IL-21).The main role of Tfh was known to help B cell differentiate and secrete antibodies.Studies had found that Tfh cells may be associated with a variety of autoimmune diseases,however,the exact role of Tfh in the MPO-AAV had not been investigated.OBJECTIVE To investigate the changes of Tfh and IL-21 in the peripheral blood from patients with MPO-AAV and explore the relationship between c Tfh and disease activity,as well as clinical damagesMETHODS 40 patients with incipient,untreated MPO-AAV patients and 30 cases healthy people were selected firstly to make the peripheral blood mononuclear cells(PBMCs).Defining CD4+CXCR5+T cells as c Tfh,and then we detected the expression of Tfh,inclouding the MFI of ICOS and PD-1 in the peripheral blood from MPO-ANCA positive vasculitis patients and healthy people with flow cytometry(FCM).The IL-21 and MPO-ANCA level in sera were detected by enzyme-linked immunosorbent assay(enzyme-linked immunosorbent assay,ELISA).Clinical data including Birmingham Vasculitis Activity Score-version 3(BVAS-V3)were collected.At last,we compared the expression differences of the various indicators between the two groups,and analyzed the correlation between these indexes in MPO-AAV patients,and detected the relationships between Tfh,IL-21 and the clinical damages.RESULTS1.The demographic characteristics: 40 people were selected in MPO-AAV group,including 17 male and 23 female,their age ranged from 23 to 85(64.43±13.36),the disease course was from 0.5 to 240(3[1,48])months,ESR was from 7 to 140(69.31±36.33)mm/h,c-reactive protein(CRP)was from 0.50 to 176.92(59.33±49.32)mg/L,and BVAS value was from 5 to 37(18.93±5.89);30 people were selected in control group,including 13 male and 17 female,their age ranged from 38 to 79(62.70±11.30).The difference of the gender and age between two groups was not statistically significant(p > 0.05);2.FCM results: the percentage of c Tfh,ICOS+c Tfh and PD-1+cTfh in MPO-AAV group were significantly higher than that in control group(25.79% ± 3.72% vs19.98%±4.72%,p<0.001;1.83%±1.06% vs 0.82%±0.60%,p<0.001;10.10%±2.85 vs 8.17%±2.66%,p=0.018).Compared with control group,the MFI of ICOS and PD-1 on c Tfh in MPO-AAV group were significantly higher(59.16±10.12 vs48.88±7.36,p<0.001;532.71±81.14 vs 449.15±65.99,p<0.001);3.ELISA results: the IL-21 level in sera was significantly higher in MPO-AAV group than that in control group(Z=4.12,p=4.12);the MPO-ANCA level(OD value)in sera from patients with MPO-AAV was 0.352 [0.248,0.433];4.The correlation analysis among test indexes in MPO-AAV group: the percentage of c Tfh was positively correlated with the serum IL-21 level and the serum MPO-ANCA level(r=0.497,p<0.01;r=0.736,p<0.01)respectively.The MFI of ICOS was significantly positive correlated with the serum IL-21 level and MPO-ANCA level(r=0.586,p<0.01;r=0.607,p<0.01)respectively.The serum IL-21 level was positively associated with the serum MPO-ANCA level(r=0.668,p<0.01);5.The correlation analysis between test indicators and clinical indicators in MPO-AAV group: the BVAS was positively associated with the percentage of c Tfh,the MFI of ICOS and the serum MPO-ANCA level(r=0.564,p<0.01;r=0.513,p<0.01;r=0.358,p<0.05)respectively;6.In MPO-AAV group,the percentage of c Tfh and the MFI of ICOS in patients with kidney damage were higher than that in patients without kidney damage,the difference was statistically significant(p<0.05).There was no significant difference between patients with pulmonary damage and patients without pulmonary damage;7.The kidney BVAS was positively correlated with the percentage of c Tfh,the MFI of ICOS(r=0.393,p<0.05;r=0.389,p<0.05)from patients with MPO-AAV,and there was no correlation between pulmonary BVAS and all the indexes.CONCLUTION1.The percentage of c Tfh,the expression level of ICOS and PD-1 on c Tfh,and the serum IL-21 level were higher in MPO-AAV group than that in control group,implying there was a disorder of c Tfh in quantity and function in MPO-AAV patients;2.There was a positive correlation between the two of the percentage of c Tfh,the serum IL-21 level and the serum MPO-ANCA level in MPO-AAV patients,suggesting that c Tfh may participate in the pathogenesis of MPO-AAV by assisting B cells to produce pathogenic antibody MPO-ANCA,and this process may be achieved by IL-21;3.The BVAS was positively correlated with the percentage of c Tfh and the MFI of ICOS on c Tfh respectively in MPO-AAV patients,implying that the quantity and function of c Tfh may participate in the occurrence and development of MPO-AAV;4.The results that involved c Tfh and kidney damage in MPO-AAV patients prompted that c Tfh may be associated with the occurrence and development of kidney damage. |
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