Hyun Ah Yoon1, Antonio Nakouzi2, Christina C Chang3, Mark H Kuniholm4, Leandro J Carreño5, Tao Wang6, Thumbi Ndung'u7,8,9,10, Sharon R Lewin3,11, Martyn A French12, Liise-Anne Pirofski1. 1. Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York. 2. Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York. 3. Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia. 4. Department of Epidemiology and Biostatistics, University at Albany, Rensselaer, New York. 5. Millennium Institute on Immunology and Immunotherapy, Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. 6. Department of Epidemiology and Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York. 7. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal. 8. Africa Health Research Institute, Durban, South Africa. 9. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge. 10. Max Planck Institute for Infection Biology, Berlin, Germany. 11. The Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital. 12. University of Western Australia Medical School and School of Biomedical Sciences, Perth, Australia.
Abstract
Background: Initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated. Methods: We compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infected patients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS. Results: Prior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells. Discussion: Antibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.
Background: Initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated. Methods: We compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infectedpatients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS. Results: Prior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells. Discussion: Antibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.
Authors: Hyunah Yoon; Antonio Nakouzi; Peter G Pappas; Vagish S Hemmige; Liise Anne Pirofski Journal: Open Forum Infect Dis Date: 2022-04-20 Impact factor: 4.423
Authors: Samuel Okurut; David B Meya; Freddie Bwanga; Joseph Olobo; Michael A Eller; Fatim Cham-Jallow; Paul R Bohjanen; Harsh Pratap; Brent E Palmer; Katharine H Hullsiek; Yukari C Manabe; David R Boulware; Edward N Janoff Journal: Infect Immun Date: 2020-02-20 Impact factor: 3.441
Authors: Admire Hlupeni; Antonio Nakouzi; Tao Wang; Kathryn F Boyd; Tariro A Makadzange; Chiratidzo E Ndhlovu; Liise-Anne Pirofski Journal: Open Forum Infect Dis Date: 2018-12-11 Impact factor: 3.835