1. Lack of elevated pre-ART elastase-ANCA levels in patients developing TB-IRIS
- Author
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Goovaerts, Odin, Massinga-Loembé, Marguerite, Ondoa, Pascale, Ceulemans, Ann, Worodria, William, Mayanja-Kizza, Harriet, Colebunders, Robert, Kestens, Luc, Loembé, Marguerite Massinga, Mayanja, Harriet, Mascart, Francoise, van den Bergh, Rafael, Locht, Camille, Reiss, Peter, Cobelens, Frank, Pakker, Nadine, Mugerwa, Roy, Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, APH - Methodology, and TB-IRIS Study Group
- Subjects
0301 basic medicine ,Male ,Bacterial Diseases ,Neutrophils ,Physiology ,HIV Infections ,Biochemistry ,White Blood Cells ,Medical Conditions ,Proteinase 3 ,Immune Reconstitution Inflammatory Syndrome ,Animal Cells ,Immune Physiology ,Blood plasma ,Immunologie ,Medicine and Health Sciences ,Medicine ,Public and Occupational Health ,Immune Response ,Multidisciplinary ,Immune System Proteins ,biology ,Pancreatic Elastase ,Lactoferrin ,Elastase ,Vaccination and Immunization ,Body Fluids ,Infectious Diseases ,Blood ,Anti-Retroviral Agents ,Myeloperoxidase ,Female ,Antibody ,Cellular Types ,Anatomy ,Engineering sciences. Technology ,Research Article ,Adult ,Tuberculosis ,Science ,Immune Cells ,030106 microbiology ,Immunology ,Antiretroviral Therapy ,Blood Plasma ,Antibodies ,Antibodies, Antineutrophil Cytoplasmic ,03 medical and health sciences ,Signs and Symptoms ,Immune reconstitution inflammatory syndrome ,Antiviral Therapy ,Humans ,cardiovascular diseases ,Inflammation ,Blood Cells ,business.industry ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,Tropical Diseases ,030112 virology ,Sciences biomédicales ,Co-Infections ,biology.protein ,Preventive Medicine ,Clinical Medicine ,business - Abstract
Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV-TB co-infected patients receiving antiretroviral therapy (ART) has been linked to neutrophil activation. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also associated with neutrophil activation. Since ANCAs are reportedly skewed in TB and HIV infections, we investigated plasma levels of 7 ANCAs in TB-IRIS patients. Methods We retrospectively compared 17 HIV-TB patients who developed TB-IRIS with controls of similar CD4 count, age and gender who did not (HIV+TB+ n = 17), HIV-infected patients without TB (HIV+TB-, n = 17) and 10 HIV-negative (HIV-TB-) controls. Frozen plasma was collected before ART, at 3 and 9 months of ART, and examined by ELISA for levels of 7 ANCAs directed against; Proteinase 3 (PR3), Myeloperoxidase (MPO), Permeability-increasing protein (BPI), Elastase, Cathepsin, Lysozyme, and Lactoferrin. Results Compared to HIV+TB+ controls, pre-ART anti-elastase levels were lower in TB-IRIS patients (p = 0.026) and HIV-TB- controls (p = 0.044), whereas other ANCAs did not show significant differences between groups at any time point. A significant decrease over time could be observed in TB-IRIS patients during ART for anti -PR3 (p = 0.027), -lysozyme (p = 0.011), and -lactoferrin (p = 0.019). Conversely, HIV+TB+ controls showed a significant decrease over time for anti -MPO (p = 0.002), -lyzosyme (p = 0.002) and -elastase (p < 0.001). Conclusion The lack of elevated anti-elastase levels in TB-IRIS patients as opposed to HIV+TB+ controls correspond to previous findings of lowered immune capacity in patients that will develop TB-IRIS. This may suggest a specific role for anti-elastase, elastase or even matrix-metalloproteinases in TB-IRIS. The precise dynamics of neutrophil activation in HIV-TB merits further investigation and could provide more insight in the early mechanisms leading up to TB-IRIS., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2020