Kapembwa, MS; Batman, PA; Fleming, SC; Griffin, GE
(2023)
HIV enteropathy and 'Slim disease': Historical and current perspectives.
Int J Infect Dis, 139.
pp. 86-91.
ISSN 1878-3511
https://doi.org/10.1016/j.ijid.2023.11.037
SGUL Authors: Griffin, George Edward
Abstract
OBJECTIVES: Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. METHODS: Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings 'HIVE', 'SD', and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. RESULTS: Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. CONCLUSION: Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies.
Item Type: |
Article
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Additional Information: |
© 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: |
HIV enteropathy, Highly active antiretroviral therapy, Immunopathogenesis, Slim disease, Animals, Humans, HIV Wasting Syndrome, HIV Infections, Fibroblast Growth Factor 7, HIV Enteropathy, Intestinal Mucosa, Diarrhea, CD4-Positive T-Lymphocytes, Intestinal Mucosa, CD4-Positive T-Lymphocytes, Animals, Humans, HIV Infections, HIV Enteropathy, HIV Wasting Syndrome, Diarrhea, Fibroblast Growth Factor 7, HIV enteropathy, Slim disease, Immunopathogenesis, Highly active antiretroviral therapy, 0605 Microbiology, 1108 Medical Microbiology, 1117 Public Health and Health Services, Microbiology |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Int J Infect Dis |
ISSN: |
1878-3511 |
Language: |
eng |
Dates: |
Date | Event |
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17 December 2023 | Published | 4 December 2023 | Published Online | 28 November 2023 | Accepted |
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Publisher License: |
Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 |
PubMed ID: |
38052315 |
Web of Science ID: |
WOS:001139603700001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/116047 |
Publisher's version: |
https://doi.org/10.1016/j.ijid.2023.11.037 |
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