An Fc receptor and IgA functional signature identifies TB disease in children living with HIV.
| Title: | An Fc receptor and IgA functional signature identifies TB disease in children living with HIV. |
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| Authors: | Kang YJ; Division of Pediatric Infectious Disease, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.; Wang N; Department of Immunology and Microbiology, University of Colorado Anshutz School of Medicine, Aurora, CO, USA.; Biostatistics & Informatics PhD Program, Colorado School of Public Health, CO, USA.; Malik A; Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA.; Lu P; Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.; Njuguna I; Medical Research Department, Kenyatta National Hospital, Nairobi, Kenya.; Department of Global Health, University of Washington, Seattle, WA, USA.; Nell Hudgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA.; Maleche-Obimbo E; Department of Global Health, University of Washington, Seattle, WA, USA.; Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya.; LaCourse SM; Department of Global Health, University of Washington, Seattle, WA, USA.; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Slyker J; Department of Global Health, University of Washington, Seattle, WA, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Wamalwa D; Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya.; John-Stewart GC; Department of Global Health, University of Washington, Seattle, WA, USA.; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Department of Pediatrics, University of Washington, Seattle, WA, USA.; Wang C; Department of Immunology and Microbiology, University of Colorado Anshutz School of Medicine, Aurora, CO, USA.; Cranmer LM; Division of Infectious Diseases, Department of Pediatrics, Emory University, Atlanta, GA, USA.; Children's Healthcare of Atlanta, Atlanta, GA, USA.; Department of Epidemiology, Emory Rollins School of Public Health, Atlanta, GA, USA.; Lu LL; Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.; Parkland Health, Dallas, TX, USA. |
| Source: | MedRxiv : the preprint server for health sciences [medRxiv] 2026 Feb 10. Date of Electronic Publication: 2026 Feb 10. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Background: Tuberculosis (TB) is a leading cause of morbidity and mortality among children living with HIV (CLHIV). Poor diagnostic performance is a significant contributor. Serological assays that determine levels of Mycobacterium tuberculosis reactive antibodies inconsistently detect TB. However, antigen-specific antibody Fc receptor engagement and effector functions are promising biomarkers of TB disease.; Methods: This study evaluated serum from a well-characterized cohort of Kenyan CLHIV via two orthogonal approaches: 1) longitudinally following over the course of TB treatment and 2) assessing a cross-section with and without clinical TB disease. For each individual sample, 13 antibody functional properties against 8 Mtb and 4 non-Mtb microbial antigens were measured and analyzed via univariate and multivariate machine-learning approaches.; Findings: FcαR/CD89 immune complex formation with antibodies reactive to four Mtb antigens including ESAT-6 & CFP-10, FcγRI/CD64 associated with one Mtb antigen, and HIV gp120 IgA1 levels decreased during the intensive and continuation/consolidation phases of TB therapy. This antibody signature also highlighted treatment non-responsiveness and distinguished children with from those without TB disease with predictive capacity similar to Xpert.; Interpretation: An Mtb and HIV reactive peripheral blood antibody functional signature of FcαR/CD89, FcγRI/CD64, and IgA1 has the potential to complement current clinical tools and those in development to diagnose pulmonary TB disease in CLHIV. |
| Competing Interests: | Declaration of interests Amyn A. Malik was employed by Analysis Group, Inc from 2022-2024. |
| Grant Information: | P30 AI168386 United States AI NIAID NIH HHS; R01 AI158858 United States AI NIAID NIH HHS; R21 AI192086 United States AI NIAID NIH HHS |
| Entry Date(s): | Date Created: 20260223 Date Completed: 20260317 Latest Revision: 20260418 |
| Update Code: | 20260418 |
| PubMed Central ID: | PMC12919122 |
| DOI: | 10.64898/2026.02.08.26345833 |
| PMID: | 41728310 |
| Database: | MEDLINE |
Journal Article; Preprint