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IGHG3 hinge length variation was associated with the risk of critical disease and death in a Spanish COVID-19 cohort. | LitMetric

AI Article Synopsis

  • IgG3 plays a key role in the immune response to SARS-CoV-2, with low levels possibly leading to worse outcomes in COVID-19 cases.
  • The study found that a specific genetic variation in the IgG3 hinge region, which results in shorter or longer forms, affects immune functions like neutralization and phagocytosis.
  • Individuals with shorter IgG3 (S allele) faced a higher risk of severe COVID-19 and mortality, highlighting the potential of this genetic marker for predicting outcomes, though further research is needed.

Article Abstract

IgG3 would play an important role in the immune adaptive response against SARS-CoV-2, and low plasma levels might increase the risk of COVID-19 severity and mortality. The IgG3 hinge sequence has a variable repeat of a 15 amino acid exon with common 4-repeats (M) and 3-repeats (S). This length IGHG3 polymorphism might affect the IgG3 effector functions. The short hinge length would reduce the IgG3 flexibility and impairs the neutralization and phagocytosis compared to larger length-isoforms. We genotyped the IGHG3 length polymorphism in patients with critical COVID-19 (N = 516; 107 death) and 152 moderate-severe but no-critical cases. Carriers of the S allele had an increased risk of critical ICU and mortality (p < 0.001, OR = 2.79, 95% CI = 1.66-4.65). This adverse effect might be explained by a less flexibility and reduced ability to induce phagocytosis or viral neutralization for the short length allele. We concluded that the IgG3 hinge length polymorphism could be a predictor of critical COVID-19 and the risk of death. This study was based on a limited number of patients from a single population, and requires validation in larger cohorts.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463670PMC
http://dx.doi.org/10.1038/s41435-022-00179-3DOI Listing

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