title: Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis.
abstract: Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4) cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), and cluster of differentiation 45 (CD45) cells, and lower percentages of CD8 cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non-PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis.
authors.affiliation: From the Department of Infectious Disease (LX, QH, C-YZ, S-KY, A-HZ, YL), Medical Inspection Department (D-HC), Department of Hepatology, Shanghai Public Health Clinical Center (LC); Dermatological Department, Huashan Hospital, Fudan University, Shanghai (J-RL, C-FZ); and Department of Infectious Diseases (X-HL), The Third Affiliated Hospital of Sun-Yat-Sen University, Guangzhou, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Xu
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Jin-Ran
authors.initials: JR
authors.lastname: Lin
authors.forename: Cui-Yun
authors.initials: CY
authors.lastname: Zhu
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Li
authors.forename: Shan-Ke
authors.initials: SK
authors.lastname: Ye
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Zhu
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Chen
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D016919:Meningitis, Cryptococcal / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G