Association of Antibody Immunity With Cryptococcal Antigenemia and Mortality in a South African Cohort With Advanced Human Immunodeficiency Virus Disease
Year: 2022
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Asymptomatic cryptococcal antigenemia (positive blood cryptococcal antigen [CrAg]) is associated with increased mortality in individuals with human immunodeficiency virus (HIV) even after adjusting for CD4 count and despite receiving antifungal treatment. The association of antibody immunity with mortality in adults with HIV with cryptococcal antigenemia is unknown. METHODS: Cryptococcal capsular glucuronoxylomannan (GXM)- and naturally occurring β-glucans (laminarin, curdlan)-binding antibodies were measured in blood samples of 197 South Africans with HIV who underwent CrAg screening and were followed up to 6 months. Associations between antibody titers, CrAg status, and all-cause mortality were sought using logistic and Cox regression, respectively. RESULTS: Compared with CrAg-negative individuals (n = 130), CrAg-positive individuals (n = 67) had significantly higher IgG1 (median, 6672; interquartile range [IQR], 4696-10 414 vs 5343, 3808-7722 μg/mL; P = .007), IgG2 (1467, 813-2607 vs 1036, 519-2012 μg/mL; P = .01), and GXM-IgG (1:170, 61-412 vs 1:117, 47-176; P = .0009) and lower curdlan-IgG (1:47, 11-133 vs 1:93, 40-206; P = .01) titers. GXM-IgG was associated directly with cryptococcal antigenemia adjusted for CD4 count and antiretroviral therapy use (odds ratio, 1.64; 95% confidence interval [CI], 1.21 to 2.22). Among CrAg-positive individuals, GXM-IgG was inversely associated with mortality at 6 months adjusted for CD4 count and tuberculosis (hazard ratio, 0.50; 95% CI, .33 to .77). CONCLUSIONS: The inverse association of GXM-IgG with mortality in CrAg-positive individuals suggests that GXM-IgG titer may have prognostic value in those individuals. Prospective longitudinal studies to investigate this hypothesis and identify mechanisms by which antibody may protect against mortality are warranted.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciac633
Institutions: Albert Einstein College of Medicine, Montefiore Medical Center, National Health Laboratory Service, St George's Hospital, St George’s University Hospitals NHS Foundation Trust, National Institute for Communicable Diseases, University of the Witwatersrand, University of Cape Town, University of Exeter, MRC Centre for Medical Mycology, London School of Hygiene & Tropical Medicine, Botswana Harvard AIDS Institute Partnership
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Bill and Melinda Gates Foundation, Pfizer, Gilead Sciences, City University of New York, Government of the United Kingdom, Georgia Clinical and Translational Science Alliance, National Institute for Health and Care Research, Department of Health and Social Care, Meningitis Research Foundation, National Research Foundation, National Health Laboratory Service, National Institutes of Health, Centers for Disease Control and Prevention, Center for AIDS Research, University of Washington, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Einstein-Rockefeller-CUNY Center for AIDS Research, Albert Einstein College of Medicine, European and Developing Countries Clinical Trials Partnership
Awards: G144555574, G27772751, G2874871036, G3786241263, G4517903627, G4769057925, G5481562151, G5610546566, G5955858001, Antibodies, B cells and resistance to human cryptococcosis, G6112613950, G6476391617, G6691054050, Phased Implementation of a Public Health Programme: Cryptococcal Screening and Treatment in South Africa, G8906178588, ERC Einstein-Rockefeller-CUNY Center for AIDS research, G954115541
OpenAlex ID: W4289522198