| ObjectiveTo dynamically monitor the changes of lymphocyte subsets in patients with lupus nephritis(LN)and antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)throughout the treatment process,and to discover and evaluate their different clinical values and significance at the different treatment nodes in order to precisely guide the diagnosis and treatment.MethodsRetrospective analysis of clinical data of 65 patients with primary LN who had tested for lymphocyte subsets hospitalized from 2015 to 2021 and 61 patients with primary AAV who had tested for lymphocyte subsets hospitalized from 2015 to 2022 at the Affiliated Hospital of Qingdao University.According to the stage of disease progression and SLEDAI score,LN patients were classified into primary active phase,post-induction therapy,and maintenance therapy phase.BVAS score were analyzed according to the BVAS score,which was divided into active and relatively remission periods.The patterns of changes in lymphocyte subsets at different treatment nodes were monitored,and the relationship between the characteristics of changes in lymphocyte subsets,and disease activity and infection events was evaluated,and one-way and multi-way logistic regression models were applied to explore the influencing factors for the occurrence of infection Statistical analysis was performed using SPSS 25.0 statistical software,and differences were considered statistically significant if P<0.05.Results(1)Blood CD4~+T lymphocyte count and NK cell ratio decreased in LN patients at initial activity and increased after induction therapy,and were significantly negatively correlated with SLEDAI-2000 scores(P<0.05);B cell and CD8~+T lymphocyte ratio increased at initial activity and decreased significantly after induction therapy,were significantly and positively correlated(P<0.05).Blood lymphocyte count,D-dimer,C3,C4,and 24-h urine protein quantification were significantly improved in LN patients after induction therapy compared with the initial active period(P<0.05).(2)Patients with LN who had type III or IV renal puncture biopsies at the time of initial presentation had lower blood CD4~+T lymphocyte counts than patients with type V.(3)The blood CD4~+T lymphocyte count and ratio and NK cell ratio decreased again during the maintenance treatment period,when the incidence of infection was highest(47.2%);when the blood CD4~+T lymphocyte count decreased to the critical value of 247.5cells/ul,the area under the ROC curve(AUC)was 0.894,and the sensitivity and specificity for predicting the occurrence of infection were 81.25%,respectively.87.50%;focusing on CRP/CD4~+T lymphocytes increased the sensitivity of infection to 94.12%,and focusing on both CRP and CD4~+T lymphocyte counts increased the predictive specificity of infection to 95%.(4)A combination of low CD4~+T lymphocyte count with low NK cell ratio and high B lymphocyte ratio suggests a highly active SLE;a combination of low CD4~+T lymphocyte count with low NK cell ratio and low B lymphocyte ratio suggests a state of severe immunosuppression.(5)BVAS score,B lymphocyte ratio and CD8~+T lymphocytes were significantly higher in AAV patients during the active phase,and B lymphocyte ratio was significantly positively correlated with BVAS score(P<0.05),while blood CD4~+T lymphocyte count and NK cell ratio were decreased,and were both significantly negatively correlated with BVAS score(P<0.05).(6)The incidence of infection was higher in the active phase than in relative remission(46.75%vs 31.78%,P=0.039);lungs were the main site of infection in AAV patients(87.14%).Multifactorial logistic regression analysis suggested that age(OR=1.131,95%CI 1.015 to 1.260,P=0.025)and blood CD4~+T lymphocyte count(OR=0.783,95%CI0.626 to 0.979,P=0.032)were independent risk factors for the development of infection in patients with AAV.(7)The combination image of low CD4~+T lymphocyte count,low NK cell ratio,high B lymphocyte ratio,high ESR,and high CRP suggests that AAV is highly active,with the most imbalanced immunity and patients most susceptible to infection;the combination image of high CD4~+T lymphocyte count,high NK cell ratio,low B lymphocyte ratio,low ESR,and low CRP suggests that AAV patients have the most stable disease and the lowest incidence of infection.Patients presenting with tn BCE in the initial phase of the disease had lower cumulative renal survival than the TNbce group(Log-rank test,χ2=4.13,P=0.042).Conclusions(1)Lymphocyte subsets can be used as a tool to determine the activity of LN and AAV.When the blood CD4~+T lymphocyte count and NK cell level are lower and the B lymphocyte level is higher,it indicates a high degree of disease activity and prompt immunosuppressive therapy should be administered.(2)Lymphocyte subpopulation is a favorable aid to judge LN and AAV infection.Considering lymphocyte subpopulation and disease activity together,the incidence of infection can be judged:when LN disease activity is low,while blood CD4~+T lymphocyte count and NK cell level are significantly lower than before,infection is most likely to occur;while in AAV,when blood CD4~+T lymphocyte count and NK cell level are significantly lower than before,and AAV is highly active,infection is most likely to occur.(3)Lymphocyte subsets can be used as a tool to predict infection:in LN patients,when blood CD4~+T lymphocyte counts decreased to 247.5cell/ul,the sensitivity and specificity to predict infection were 81.25%and 87.50%,focusing on CRP/CD4~+T lymphocytes increased the sensitivity of infection to 94.12%,and focusing on both CRP and CD4~+T lymphocyte count could increase the predictive specificity of infection to 95%;while in AAV,blood CD4~+T lymphocytes and age were independent risk factors for the development of infection.(4)Blood CD4~+T lymphocytes are more significantly decreased in primary active proliferative LN than in membranous LN.(5)The combination of each cell linkage of lymphocyte subpopulation can precisely determine the disease status:in LN,the combined phase of low CD4~+T lymphocyte count,low NK cell ratio,and high B lymphocyte ratio suggests a highly active LN,and the combined phase of low CD4~+T lymphocyte count,low NK cell ratio,and low B lymphocyte ratio suggests a state of severe immunosuppression in LN,when infection is most likely to occur;in AAV In AAV,the combination of lymphocyte subpopulation with ESR and CRP,the combination of low CD4~+T lymphocyte count,low NK cell ratio,high B lymphocyte ratio,high CRP,and high ESR suggests a highly active AAV,when infection is most likely to occur,while the combination of high CD4~+T lymphocyte count,high NK cell ratio,low B lymphocyte ratio,low ESR,and low CRP suggests a highly active AAV,when infection is most likely to occur.The combination of high CD4~+T lymphocyte count,high NK cell ratio,low B lymphocyte ratio,low ESR,and low CRP suggests that AAV patients are most stable and have the lowest incidence of infection.(6)The combination of each cell linkage of lymphocyte subpopulation can be used as a tool to determine the prognosis of AAV.The lower the blood CD4~+T lymphocyte count and NK cell level at the initial diagnosis,and the higher the level of B cells,CRP and ESR,the worse the renal prognosis. |
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