Abstract | BACKGROUND: METHOD: HIV-infected patients with cryptococcal meningitis who experienced C-IRIS (n = 27) were compared with CD4 T-cell count-matched counterparts without C-IRIS (n = 27), after antifungal therapy and pre-ART initiation. Flow cytometry was used to assess T-cell and monocyte phenotypes and functions. RESULTS: Proportions of IL-7R+ CD4 or CD8 T cells correlated positively with CD4 T-cell counts and proportions of central memory and naive CD4 and CD8 T-cell pre-ART (all r > 0.50 and P < 0.05); however, the former negatively correlated with CD4 T-cell counts fold-increase on ART in non-C-IRIS but not C-IRIS patients. Higher frequencies of activated monocytes (CD14CD86 or CD14+HLA-DR+; P ≤ 0.038) were also observed in C-IRIS compared with non-C-IRIS patients, and those who failed to clear cryptococci from cerebrospinal fluid before ART had higher levels of activated monocytes (CD14+HLA-DR+, P = 0.017) compared with those who cleared. In multivariate regression, CD14+HLA-DR+ monocytes were independently associated with C-IRIS [hazard ratio = 1.055 (1.013-1.098); P = 0.009]. CONCLUSION: In contrast to non-C-IRIS patients, C-IRIS patients displayed a lack of association between proportions of IL-7R+ T cells and several markers of T-cell homeostasis. They also exhibited higher monocyte activation linked to cerebrospinal fluid cryptococcal culture positivity before ART. These data suggest a role for IL-7/IL-7R signaling pathway dysregulation in the pathogenesis of C-IRIS, possibly linked to monocyte activation and residual pathogen burden before ART.
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Authors | Ngomu Akeem Akilimali, Daniel M Muema, Charles Specht, Christina C Chang, Mahomed-Yunus S Moosa, Stuart M Levitz, Sharon R Lewin, Martyn A French, Thumbi Ndungʼu |
Journal | Journal of acquired immune deficiency syndromes (1999)
(J Acquir Immune Defic Syndr)
Vol. 80
Issue 5
Pg. 596-604
(04 15 2019)
ISSN: 1944-7884 [Electronic] United States |
PMID | 30649031
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-HIV Agents
- IL7 protein, human
- Interleukin-7
- Receptors, Interleukin-7
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Topics |
- Adolescent
- Adult
- Anti-HIV Agents
(adverse effects, therapeutic use)
- CD4 Lymphocyte Count
- Case-Control Studies
- Coinfection
(immunology, microbiology, virology)
- Cryptococcosis
(complications, immunology)
- Flow Cytometry
- HIV Infections
(complications, immunology, metabolism, microbiology)
- Humans
- Immune Reconstitution Inflammatory Syndrome
(metabolism)
- Interleukin-7
(metabolism)
- Lymphocyte Activation
- Monocytes
(metabolism)
- Receptors, Interleukin-7
(metabolism)
- Retrospective Studies
- Signal Transduction
- T-Lymphocytes
(metabolism)
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