Association of infection with Toxoplasma gondii and arthritis: Insights from a cross-sectional study and genetic epidemiology analysis.

BACKGROUND

Toxoplasma gondii (T. gondii), a ubiquitous protozoan infecting one-third of humanity, exhibits complex immunomodulatory properties. While experimental models suggest paradoxical roles in inflammation regulation, epidemiological data linking T. gondii to arthritis remain inconclusive, and the genetic causality unexplored. This multidisciplinary study integrates population epidemiology with genetic epidemiology to elucidate this relationship.

METHODS

Analyzing 17,029 U S. adults from NHANES, we performed multivariable-adjusted logistic regression with complex survey weighting. Genetic correlations were assessed via linkage disequilibrium score regression (LDSC), complemented by bidirectional two-sample Mendelian randomization (MR) using GWAS data for three T. gondii serological markers (IgG, p22, sag1) and arthritis phenotypes.

RESULTS

T. gondii IgG seropositivity showed significant association with arthritis prevalence after multivariable adjustment (OR = 1.19, 95 % CI:1.03-1.38). Racial disparities were prominent, particularly in non-Hispanic whites across overall arthritis, rheumatoid arthritis (RA), and osteoarthritis (OA) (all Pinteraction<0.05). LDSC and forward MR revealed no genetic correlation or causal effect of T. gondii infection on arthritis phenotypes risk (all P > 0.05). Reverse MR demonstrated reduced T. gondii sag1 IgG levels in RA (OR = 0.92, 95 % CI:0.87-0.98) and OA (OR = 0.63, 95 % CI:0.44-0.88), suggesting impaired anti-parasitic humoral immunity.

CONCLUSION

Our study reveals a complex duality: while chronic T. gondii exposure correlates with arthritis susceptibility in specific populations, the genetic evidence proposes a paradigm-shifting mechanism - autoimmune dysregulation in arthritis may compromise anti-parasitic antibody responses. This bidirectional relationship advances our understanding of infection-autoimmunity crosstalk, with critical implications for managing parasitic co-infections in rheumatological care.