Effects Of Hydroxychloroquine On Intestinal Homing (CCR9~+β7~+)B Lymphocytes And Baff In Peripheral Blood Of IgA Nephropathy

【Objective】IgA nephropathy(IgAN)is one of the most common primary glomerulonephritis and lacks specific treatment.Hydroxychloroquine(HCQ)is an immunomodulator that has shown promising results in the treatment of IgAN,and the 2021 KDIGO guidelines mention that HCQ can be used in IgAN patients at higher risk of progression.However,the specific therapeutic mechanism of HCQ in treating IgAN remains unclear.This study intends to detect the abnormal expression of four subpopulations of peripheral blood intestinal homing(CCR9~+β7~+)B lymphocytes(naive B cells,memory B cells,plasmablasts and Bregs)and B-cell activating factor(BAFF)during HCQ treatment in IgAN patients.This study was conducted to analyse some of the mechanisms of intervention of HCQ on the abnormal immune response associated with IgAN intestinal mucosa.【Methods】A total of 35 patients admitted to the Department of Nephrology,Subei People’s Hospital from December 2021 to December 2022 and diagnosed as primary IgAN for the first time by renal puncture biopsy were selected.And according to different treatment regimens at enrollment,they were divided into three groups:HCQ group(12cases),HCQ+hormone group(11 cases)and renin-angiotensin-aldosterone system inhibitors(RAASi)group(12 cases).General data,clinical data,pathological specimens and peripheral venous blood specimens of the three groups were collected respectively.The gut-homing(CCR9~+β7~+)B lymphocytes(naive B cells,memory B cells,plasmablasts and Bregs)in peripheral blood were detected by flow cytometry.Serum BAFF levels were detected by ELISA.Changes in the percentage of the four intestinal homing(CCR9~+β7~+)B lymphocyte subpopulations and serum BAFF levels at month 0,1 and 6 of treatment in the three groups were analysed and correlation analysis was used to explore the relationship between them and clinical indicators.【Results】1.The expression of peripheral blood intestinal homing(CCR9~+β7~+)memory B cells and(CCR9~+β7~+)plasmablasts decreased in both the HCQ and HCQ+hormone groups at the 1st and 6th month of treatment compared with pre-treatment,and the difference was statistically significant(P<0.05);2.A statistically significant(P<0.05)decrease in serum BAFF levels in the HCQ and HCQ+hormone groups at the 6th month of treatment compared with pre-treatment;3.There was no statistically significant difference(P>0.05)in urine protein levels between the three groups before treatment.The difference between the three groups was statistically significant(P<0.01).The decrease in urine protein level in the HCQ+hormone group was more significant compared with the other two groups(P<0.05).4.The difference between peripheral blood intestinal homing(CCR9~+β7~+)memory B cells at the 6th month of treatment and before treatment in the HCQ group was positively correlated with the difference in urine protein(r=0.649,P=0.031).5.A positive correlation between the difference in serum BAFF levels and the difference in urine protein at month 6 versus pre-treatment in the HCQ group(r=0.607,P=0.048).【Conclusions】1.HCQ inhibited the expression of intestinal homing(CCR9~+β7~+)memory B cells,plasmablasts and serum BAFF in patients with primary IgAN,suggesting that HCQ may be involved in reducing the high humoral immune response in the intestine.2.HCQ was effective in reducing urinary protein levels in primary IgAN patients,with more significant levels of reduction in urinary protein at the 6th month in the HCQ+hormone group compared to the HCQ alone group,but with more adverse effects.3.HCQ can reduce urinary protein levels in primary IgAN patients,and the mechanism may be achieved by reducing peripheral blood intestinal homing(CCR9~+β7~+)memory B cells and serum BAFF levels.