title: Impaired thymic function and CD4+ T lymphopenia, but not mannose-binding lectin deficiency, are risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients.
abstract: Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in kidney transplant recipients (KTR), but risk factors remain poorly defined. CD4+ T lymphopenia and mannose-binding lectin (MBL) deficiency are common immunodeficiencies in KTR. Here, we investigated whether CD4+ T lymphopenia and/or MBL deficiency would be risk factors for PCP in KTR. Furthermore, the role of thymic function in CD4+ T lymphopenia and outcome was studied by assessing CD45RA+CD31+CD4+ T cell numbers (RTE, recent thymus emigrants). In 321 de novo KTR serial determinations of peripheral T lymphocyte subsets (n=281, mean 4.2 times between days 0-365) and/or MBL levels (n=112, mean 1.8 times between days 30-180) were performed. 22/321 patients developed a PCP episode on average at day 199 (107-398) post-Tx. Age correlated inversely with RTE, CD4+ and CD8+ T-cell counts until day 180 post-Tx. RTE correlated with CD4+ T-cell counts at all time-points pre- and post-Tx. PCP patients had more CMV infections (p=0.045) within the first 3 months compared to controls. Importantly, PCP patients were older (p=0.008), and had lower RTE (p=0.046) pretransplant, and lower CD4+ T-cell counts pretransplant (p=0.017), at day 60 (p=0.032) and for the average of all post-Tx values (p=0.027) compared to controls. Though treatment with T-cell depleting antibodies was associated with consecutive CD4+ T lymphopenia in the whole cohort, the number of patients who received T-cell depleting antibodies was comparable between PCP and control patients (p=0.754). A multivariate stepwise logistic regression model identified only pretransplant CD4+ T-cell counts (OR 0.011, p=0.010) and acute rejection (OR 4.66, p=0.023) as predictors of PCP. In contrast, MBL levels and incidence of MBL deficiency (<500 ng/ml) at days 30, 90 and 180 post-Tx were not different between PCP patients and controls. In conclusion, PCP risk was associated with higher age and related to both thymic functional impairment and long-lasting CD4+ T-lymphopenia that started already before transplantation. Despite frequent occurrences in KTR, low levels of serum MBL were not associated with increased risk for PCP. CD4+ T-cell counts and function should be addressed in prospective studies for more individualized approaches to PCP prophylaxis.
authors.affiliation: Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Mariana
authors.initials: M
authors.lastname: Schürmann
authors.forename: Dirk
authors.initials: D
authors.lastname: Schürmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Schindler
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
authors.forename: Peter
authors.initials: P
authors.lastname: Liman
authors.forename: Jan
authors.initials: J
authors.lastname: Kruse
authors.forename: Philipp
authors.initials: P
authors.lastname: Enghard
authors.forename: Julian
authors.initials: J
authors.lastname: König
authors.forename: Danilo
authors.initials: D
authors.lastname: Schmidt
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Peter
authors.initials: P
authors.lastname: Nickel
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects*; D018655:Lymphocyte Count; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000276:immunology; D008661:Metabolism, Inborn Errors / Q000276:immunology*; D008875:Middle Aged; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000453:epidemiology*; D012307:Risk Factors; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D037601:Mannose-Binding Lectin
keywords: CD4+ T-lymphopenia; Kidney transplantation; Mannose binding lectin deficiency; Pneumocystis pneumonia