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

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 o, MD, PhD, and Min Chen, MD, PhD 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 (P1⁄4 0.02 and 0.04), pulmonary interstitial fibrosis (P1⁄4 .04 and .05), pulmonary nodule or cavity (P1⁄4 0.002 and .002), CD4 count (P< 0.001) or TLC (P1⁄4 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)CD4 count (62.8–70.2%) was almost always higher than AUC(t)TLC (55.2– 58.1%) during the first 2 years of immunosuppressive therapy (P1⁄4 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. (Medicine 94(18):e843) Abbreviations: AAV = ANCA-associated vasculitis, ANCA = antineutrophil cytoplasmic antibody, AUC = area under the ROC curve, BVAS = Birmingham Vasculitis Activity Score, CCr = creatinine clearance ratio, CD4 count = CD4 positive T lymphocyte count in the peripheral blood, CI = confidence interval, EGPA = eosinophilic granulomatosis with polyangiitis, ELISA = enzymelinked immunosorbent assay, GPA = granulomatosis with polyangiitis, IIF = indirect immunofluorescence, MPA = microscopic polyangiitis, MPO = myeloperoxidase, PR3 = proteinase 3, ROC = receiver operator characteristics, SD = standard deviation, SE = standard error, SMZ/TMP = trimethoprim-sulfamethoxazole, TLC = total lymphocyte count in the peripheral blood. INTRODUCTION A ntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal-limited vasculitis (RLV). AAV is characterized by pauci-immune necrotizing small-vessel vasculitis and glomerulonephritis, combined with granulomatous inflammation in the airways he presence of ANCA is a hallmark of t antigens of ANCAs in the AAV are myeloperoxidase (MPO). www.md-journal.com | 1 Medicine Volume 94, Number 18, May 2015 Untreated AAV has a poor prognosis, with a mortality of approximately 80% in the first year. The introduction of cyclophosphamide and corticosteroids substantially improves the prognosis, with cumulative survival rates at 1 and 5 years of approximately 82% and 76%, respectively. Nevertheless, secondary infections, rather than active vasculitis, have become the main cause of early mortality. Therefore, identifying risk factors for infection is of great clinical significance. A variety of markers, including serum IgG concentration, leukocyte count, neutrophil count, total lymphocyte count (TLC), lymphocyte subsets count and cytokine release, have been investigated to evaluate the immune status and infection risk of the immunocompromised population with different conditions. Among them, the TLC and CD4 count are commonly used as markers of immune status in predicting opportunistic infections in HIV-infected patients and Pneumocystis pneumonia infection in other immunocompromised populations. The CD4 count has been confirmed to be superior to the TLC in HIV-infected patients. Whether this finding is also the case for predicting the overall infectious complications in AAV was unclear, although lymphopenia has been identified to be an important risk factor for infection in AAV patients. Therefore, the current study aimed to investigate the role of the CD4 count in predicting infections in AAV and to compare its predictive value with that of the TLC.