899. Association of decreased cryptococcal antibody levels with cryptococcosis-associated immune reconstitution inflammatory syndrome
Session: Oral Abstract Session: Opening the Hood and Looking at the Mechanisms
Friday, October 28, 2016: 8:30 AM
Room: 388-390

Serological biomarkers of risk for cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) in patients with human immunodeficiency virus (HIV) - associated cryptococcal meningitis (CM) have not been identified. We determined the relationship between Cryptococcus neoformans(CN) specific and non-specific antibody levels and risk for C-IRIS.


We determined CN glucuronoxylomannan (GXM) and laminarin (Lam, a β 1–3 cell wall glucan) antibody titers by ELISA and total immunoglobulin levels by a luminex-based assay in plasma samples obtained before initiation of antiretroviral therapy (ART) ~ 18 days after the start of antifungal therapy from a previously reported cohort of 89 patients with HIV-associated CM (Chang CC, et al. AIDS 2013, 27:2089-99) that included 26 patients who developed C-IRIS after ART initiation and 63 patients who did not (no-C-IRIS). Statistical analysis was performed using logistic regression models with adjustment for age, sex, HIV viral load and CD4 level.


CD4 cell counts were lower in the C-IRIS than no-C-IRIS group (medians: 14 vs. 35 cells/µL respectively; P=0.06). GXM IgM, Lam IgM, Lam IgG and total IgM were each significantly inversely associated with C-IRIS independent of each adjustment factor including CD4 level. The strongest association with C-IRIS was log2 total IgM (odds ratioadjusted=0.3; 95% confidence interval=0.2-0.6; P=0.0002).


Lower levels of pre-ART GXM IgM, Lam IgM, Lam IgG, and total IgM were each associated with development of C-IRIS independent of CD4 level. Deficiency of serum IgM and B-1 B cells has been associated with aberrant pulmonary inflammatory patterns and fungal dissemination from lungs to brain in mice. As B-1 B cells produce natural and Lam IgM in mice, reduced total and/or Lam IgM in patients could reflect a loss of IgM memory B cells. This question along with the biological function of circulating IgM and Lam antibodies are now under investigation in our laboratory. Further work to determine whether reduced IgM and/or Lam antibodies portend risk for ART-associated C-IRIS is warranted.

Hyun Ah Yoon, MD1, Mark H. Kuniholm, PhD2, Antonio Nakouzi, BA3, Christina Chang, MD, PhD4, Martyn French, MD5 and Liise-Anne Pirofski, MD, FIDSA1, (1)Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, (2)Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, (3)Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, (4)Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia, (5)Department of Clinical Immunology and Immunogenetics, University of Western Australia, Perth, Australia


H. A. Yoon, None

M. H. Kuniholm, None

A. Nakouzi, None

C. Chang, None

M. French, None

L. A. Pirofski, None

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