Per- and Polyfluoroalkyl Substances (PFAS) and the Immune System

Abstract

Abstract

Background Per- and polyfluoroalkyl substances (PFAS) refer to a broad range of synthetic, highly fluorinated, and environmentally persistent compounds known for their amphipathic properties and exceptional stability against chemical and thermal degradation. These substances are recognized as endocrine disruptors, and their widespread presence has led to constant exposure. Recent research highlights their impact on human vaccine responses, suggesting a potential immunomodulatory effect.

Objective

This systematic review aims to investigate the impact of PFAS exposure, specifically the legacy compounds PFOA and PFOS, on the immune system.

Methods The MEDLINE/PubMed database was searched for publications between March 1, 2015, and 2025 concerning human studies on PFAS exposure and its effects on the immune system. Studies eligible for inclusion underwent a quality assessment using the GRADE approach for each study.

Results Thirty-five articles were identified that matched the inclusion criteria and were thus included in the systematic review. Of these, six were related to the innate and adaptive immune system, seven to asthma and allergy, and twenty-two to cancer. The findings are both suggestive and contradictory of an association between PFAS and the immune system, with a handful reporting null results.

Conclusion

Overall, no definitive relationship between PFAS and the declared health outcomes can be concluded. The body of epidemiological evidence suggests plausible links between PFAS exposure and immunological disruption, asthma- and allergy-driven disease, and carcinogenesis. This area of research requires further research to draw any conclusions.