Language
English
Publication Date
8-8-2025
DOI
10.1172/jci.insight.191951
PMID
40608426
PMCID
PMC12333951
PubMedCentral® Posted Date
7-3-2025
PubMedCentral® Full Text Version
Post-print
Abstract
MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between MICBG406A and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower airway. We identified 560 major allele homozygous patients, and 426 and 50 with 1 or 2 copies of the variant allele, respectively. MICBG406A conferred reduced odds of severe COVID-19. MICBG406A homozygous participants demonstrated 34% reduced cumulative odds for mechanical ventilation or death and 43% reduced risk for mortality. Patients with MICBG406A variant alleles had reduced soluble inflammatory mediators and differential regulation of multiple immune pathways. These findings demonstrate a potentially novel association between increasing MICBG406A variant allele copies and reduced COVID-19 severity, independent of SARS-CoV-2 viral burden and humoral immunity, suggesting the NKG2D-ligand pathway as an intervention target.
Keywords
Humans, Male, Female, COVID-19, Middle Aged, Acute Lung Injury, Respiration, Artificial, Histocompatibility Antigens Class I, SARS-CoV-2, Aged, Adult, Polymorphism, Single Nucleotide, Alleles
Published Open-Access
yes
Recommended Citation
Pickering, Harry; Alipanah-Lechner, Narges; Chen, Ernie; et al., "MICBG406A Polymorphism Reduces Risk of Mechanical Ventilation and Death During Viral Acute Lung Injury" (2025). Faculty and Staff Publications. 4646.
https://digitalcommons.library.tmc.edu/baylor_docs/4646