Anti-Toxocara canis seroreactivity across autoimmune rheumatic diseases with exploratory IgG4 and eosinophil-associated signals in systemic lupus erythematosus: a cross-sectional case-control study

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Helminth-related immune responses may intersect with autoimmune rheumatic diseases, but disease-specific patterns remain incompletely understood. This study aimed to investigate anti-Toxocara canis seroreactivity and its immunological and clinical correlates in rheumatoid arthritis, systemic lupus erythematosus, and spondyloarthritis. In this cross-sectional case-control study, 442 individuals were evaluated across disease-specific comparisons. Serology followed a sequential strategy using native T. canis excretory-secretory antigen for initial IgG screening and a recombinant chimeric antigen for confirmatory IgG, IgG1, and IgG4 assessment. Cytokines, eosinophil counts, socioeconomic variables, disease activity, and functional disability were analyzed using adjusted regression models. Total anti-T. canis IgG seroreactivity was frequent across groups. Higher adjusted point estimates were observed in rheumatoid arthritis, systemic lupus erythematosus, and spondyloarthritis. SLE was the only disease group showing a nominally significant association with IgG seroreactivity compared with its respective control group (OR 2.44, 95% CI 1.16-5.14), although no serological association remained significant after FDR correction. SLE also showed a nominal signal of lower IgG4 seroreactivity than controls in the standard adjusted model (OR 0.20, 95% CI 0.04-0.99), but this finding did not remain significant after FDR correction or in small-cell sensitivity analyses. Higher eosinophil counts were associated with lower SLEDAI scores in negative binomial models (IRR per 100 eosinophils/mm³: 0.56, 95% CI 0.36-0.86), and this association persisted after adjustment for medication use, although it should be interpreted as exploratory given the low SLEDAI distribution and limited number of active disease events. Anti-T. canis seroreactivity was frequent across autoimmune rheumatic diseases and showed disease-specific exploratory patterns. In SLE, higher total IgG seroreactivity coexisted with a cautious, hypothesis-generating IgG4 signal, while eosinophil counts showed an exploratory independent association with lower SLEDAI scores. These findings suggest that helminth-related immune signatures may vary across autoimmune disease contexts and should be interpreted as exploratory associations rather than evidence of active infection or causal immunomodulation.

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