title: The CD4 Lymphocyte Count is a Better Predictor of Overall Infection Than the Total Lymphocyte Count in ANCA-Associated Vasculitis Under a Corticosteroid and Cyclophosphamide Regimen: A Retrospective Cohort.
abstract: Patients with antineutrophil cytoplasmic autoantibody associated vasculitis (AAV) have a high prevalence of infection during immunosuppressive therapy, and the total lymphocyte count (TLC) has been demonstrated to be an independent predictor of infection. The current study investigated the value of the TLC and its subsets, particularly the CD4 count, for predicting infections of AAV in a single Chinese cohort.A total of 124 AAV patients were retrospectively recruited in our department from December 1997 to October 2013. Multivariate Cox models with the CD4 count or TLC measured at three typical time points, that is, at baseline, at the beginning of immunosuppressant dose reduction, and at the last visit before infection or censoring, or with the measurements included as time-varying covariates, were compared to select the most predictive time point for infection. A time-dependent area under the receiver operating characteristic curve (AUC(t)) for the TLC (AUC(t)TLC) and the CD4 count (AUC(t)CD4count) measured at the most predictive time point were calculated and compared.During an average follow-up of 11.5 (range 0.5-142) months, 55 of the 124 patients (44.3%) experienced a microbiologically confirmed infection. Independent predictors of overall infection were initial creatinine clearance (P = 0.02 and 0.04), pulmonary interstitial fibrosis (P = .04 and .05), pulmonary nodule or cavity (P = 0.002 and .002), CD4 count (P < 0.001) or TLC (P = 0.05) from the last visit. The comparison of Cox models fitted at different time points confirmed the last visit to be the most predictive one for overall infection. The predictive value of the CD4 count or TLC from the last visit measured by AUC showed that the AUC(t)CD4count (62.8-70.2%) was almost always higher than AUC(t)TLC (55.2-58.1%) during the first 2 years of immunosuppressive therapy (P = 0.01-0.2). In terms of different pathogens, both the CD4 count and TLC performed well for non-bacterial infection (AUC(t) 69.2-82.7%), and the difference between them was not significant (P > 0.1).The TLC and CD4 count were both independent risk factors of overall infection and non-bacterial infection in AAV patients. The CD4 count had a higher predictive value than the TLC for overall infections, particularly during the first 2 years of immunosuppressive therapy.
authors.affiliation: From the Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education.
authors.forename: Yi-Yun
authors.initials: YY
authors.lastname: Shi
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Li
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D018791:CD4 Lymphocyte Count; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007239:Infections / Q000175:diagnosis / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide