Association of infection with Toxoplasma gondii and arthritis: Insights from a cross-sectional study and genetic epidemiology analysis.
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| Titel: | Association of infection with Toxoplasma gondii and arthritis: Insights from a cross-sectional study and genetic epidemiology analysis. |
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| Autoren: | Zhu D; Department of Clinical Laboratory, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province, China., Li H; Department of Clinical Laboratory, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province, China; Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China., Zhang C; Department of Clinical Laboratory, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province, China., Zhou Y; Department of Clinical Laboratory, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province, China., Yang J; Department of Clinical Laboratory, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province, China., Feng C; Department of Clinical Laboratory, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province, China. Electronic address: fengcz_lyg@foxmail.com. |
| Quelle: | Microbial pathogenesis [Microb Pathog] 2025 Dec; Vol. 209, pp. 108086. Date of Electronic Publication: 2025 Oct 01. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Academic Press Country of Publication: England NLM ID: 8606191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-1208 (Electronic) Linking ISSN: 08824010 NLM ISO Abbreviation: Microb Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London ; Orlando : Academic Press, c1986- |
| MeSH-Schlagworte: | Toxoplasmosis*/epidemiology , Toxoplasmosis*/complications , Toxoplasmosis*/genetics , Toxoplasmosis*/immunology , Toxoplasma*/immunology , Toxoplasma*/pathogenicity , Arthritis*/epidemiology , Arthritis*/genetics, Humans ; Cross-Sectional Studies ; Antibodies, Protozoan/blood ; Male ; Adult ; Female ; Immunoglobulin G/blood ; Middle Aged ; Genome-Wide Association Study ; United States/epidemiology ; Mendelian Randomization Analysis ; Linkage Disequilibrium ; Prevalence ; Nutrition Surveys ; Arthritis, Rheumatoid/epidemiology ; Arthritis, Rheumatoid/genetics ; Genetic Predisposition to Disease ; Molecular Epidemiology |
| Abstract: | Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 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 P 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. (Copyright © 2025 Elsevier Ltd. All rights reserved.) |
| Contributed Indexing: | Keywords: Arthritis; Causality; Genetic correlation; Mendelian randomization (MR); Toxoplasma gondii |
| Substance Nomenclature: | 0 (Antibodies, Protozoan) 0 (Immunoglobulin G) |
| Entry Date(s): | Date Created: 20251003 Date Completed: 20251030 Latest Revision: 20251031 |
| Update Code: | 20251031 |
| DOI: | 10.1016/j.micpath.2025.108086 |
| PMID: | 41043595 |
| Datenbank: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br />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.<br />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.<br />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 P <subscript>interaction</subscript> <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.<br />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.<br /> (Copyright © 2025 Elsevier Ltd. All rights reserved.) |
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| ISSN: | 1096-1208 |
| DOI: | 10.1016/j.micpath.2025.108086 |