Glucose-6-phosphate dehydrogenase deficiency and long-term risk of immune-related disorders

Front Immunol. 2023 Sep 11:14:1232560. doi: 10.3389/fimmu.2023.1232560. eCollection 2023.

Abstract

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study aimed to assess the long-term health risks associated with G6PD deficiency.

Methods: A retrospective cohort study was conducted using data from a national healthcare provider in Israel (Leumit Health Services). A total of 7,473 G6PD-deficient individuals were matched with 29,892 control subjects in a 1:4 ratio, based on age, gender, socioeconomic status, and ethnic groups. The exposure of interest was recorded G6PD diagnosis or positive G6PD diagnostic test. The main outcomes and measures included rates of infectious diseases, allergic conditions, and autoimmune disorders between 2002 and 2022.

Results: Significantly increased rates were observed for autoimmune disorders, infectious diseases, and allergic conditions in G6PD-deficient individuals compared to the control group. Specifically, notable increases were observed for rheumatoid arthritis (odds ratio [OR] 2.41, p<0.001), systemic lupus erythematosus (OR 4.56, p<0.001), scleroderma (OR 6.87, p<0.001), pernicious anemia (OR 18.70, p<0.001), fibromyalgia (OR 1.98, p<0.001), Graves' disease (OR 1.46, p=0.001), and Hashimoto's thyroiditis (OR 1.26, p=0.001). These findings were supported by elevated rates of positive autoimmune serology and higher utilization of medications commonly used to treat autoimmune conditions in the G6PD-deficient group.

Discussion: In conclusion, individuals with G6PD deficiency are at a higher risk of developing autoimmune disorders, infectious diseases, and allergic conditions. This large-scale observational study provides valuable insights into the comprehensive association between G6PD deficiency and infectious and immune-related diseases. The findings emphasize the importance of considering G6PD deficiency as a potential risk factor in clinical practice and further research is warranted to better understand the underlying mechanisms of these associations.

Keywords: G6PD deficiency; allergy; autoimmunity; fibromyalgia; hidradenitis suppurativa; infectious diseases; lupus (SLE); rheumatoid arthritis.

Publication types

  • Observational Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Arthritis, Rheumatoid*
  • Autoimmune Diseases* / epidemiology
  • Glucosephosphate Dehydrogenase Deficiency* / epidemiology
  • Graves Disease*
  • Humans
  • Hypersensitivity*
  • Retrospective Studies

Substances

  • G6PD protein, human

Grants and funding

This research was supported in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, and decision to submit the manuscript for publication. The National Cancer Institute did approve the manuscript via a formal publication clearance process applied to all manuscripts.