Development of Rheumatoid Arthritis by Toxoplasmosis in Iranian Patients

Document Type : Short Communication


1 Department of Laboratory Sciences, School of Allied Medical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran

2 Quality Management, Giti Tajhiz Teb, Tehran, Iran

3 Medical Education Development Center, North Khorasan University of Medical Sciences, Bojnurd, Iran

4 Department of Parasitology and Mycology, School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran

5 Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran


Background: Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite capable of infecting approximately one-third of the world human population. In this study, the seroprevalence of Toxoplasma gondii (T. gondii) antibodies in Iranian patients with rheumatoid arthritis was investigated, given the lack of information on the magnitude of toxoplasmosis in these patients.
Methods: The serum was collected from patients with rheumatoid arthritis (n = 93) and a healthy control group (n = 93) from central parts of Iran to investigate the prevalence of anti-T. gondii IgG and IgM antibodies.
Results: Anti-T. gondii IgG was detected among 76 of 93 patients with rheumatoid arthritis (81.72%) versus 37 of 93 healthy control group (39.80%), and it was higher among patients with rheumatoid arthritis than controls. The seroprevalence of anti-T. gondii IgM was significantly higher in patients with rheumatoid arthritis (36 of 93; 38.70%) compared to the healthy control group (2 of 93; 2.1%). Demographic variables (age and sex) did not have significant correlations in patients with rheumatoid arthritis who were positive for T. gondii infection.
Conclusion: The findings of the present study provide efficient evidence that confirm the association between toxoplasmosis and development of rheumatoid arthritis, suggesting that Toxoplasma may contribute to the rheumatoid arthritis pathogenesis.


  1. Jones JL, Dubey JP. Waterborne toxoplasmosis--recent developments. Exp Parasitol 2010; 124(1):10-25. doi: 10.1016/j.exppara.2009.03.013.
  2. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004; 363(9425):1965-76. doi: 10.1016/S0140-6736(04)16412-X.
  3. Samojłowicz D, Twarowska-Małczyńska J, Borowska-Solonynko A, Poniatowski ŁA, Sharma N, Olczak M. Presence of Toxoplasma gondii infection in brain as a potential cause of risky behavior: a report of 102 autopsy cases. European Eur J Clin Microbiol Infect Dis 2019; 38(2):305-17. doi: 10.1007/s10096-018-3427-z.
  4. Flegr J, Prandota J, Sovičková M, Israili ZH. Toxoplasmosis–a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PloS One 2014; 9(3):e90203. doi: 10.1371/journal.pone.0090203.
  5. Sarkari B, Shafiei R, Zare M, Sohrabpour S, Kasraian L. Seroprevalence and molecular diagnosis of Toxoplasma gondii infection among blood donors in southern Iran. J Infect Dev Ctries 2014; 8(04):543-7. doi: 10.3855/jidc.3831.
  6. Abdollahian E, Shafiei R, Mokhber N, Kalantar K, Fata A. Seroepidemiological study of Toxoplasma gondii infection among psychiatric patients in Mashhad, Northeast of Iran. Iran J Parasitol 2017; 12(1):117-122.
  7. Rezaei F, Sarvi S, Sharif M, Hejazi SH, Pagheh AS, Aghayan SA, et al. A systematic review of Toxoplasma gondii antigens to find the best vaccine candidates for immunization. Microb Pathog 2018; 126:172-84. doi: 10.1016/j.micpath.2018.11.003.
  8. Sekandarpour S, Jafari  Modrek  M, Shafiei  R, Mohammadiha  A,  Etemadi  S,  Mirahmadi  Determination  of parasitic  burden  in the brain  tissue  of infected  mice  in acute  toxoplasmosis after treatment  by fluconazole  combined with sulfadiazine  and pyrimethamine.  Eur J Med Res 2021; 26:65.
  9. Tavalla M, Asgarian F, Kazemi F. Prevalence and genetic diversity of Toxoplasma gondii oocysts in cats of southwest of Iran. Infection, Disease & Health 2017; 22(4):203-9. doi: 10.1016/j.idh.2017.08.003.
  10. Weiss LM, Kim K. The development and biology of bradyzoites of Toxoplasma gondii. Front Biosci 2000; 5:D391-405. doi: 10.2741/weiss.
  11. Wang ZD, Liu HH, Ma ZX, Ma HY, Li ZY, Yang ZB, et al. Toxoplasma gondii infection in immunocompromised patients: a systematic review and meta-analysis. Front Microbiol 2017; 8:389. doi: 10.3389/fmicb.2017.00389.
  12. Sensini A. Toxoplasma gondii infection in pregnancy: opportunities and pitfalls of serological diagnosis. Clin Microbiol Infect 2006; 12(6):504-12. doi: 10.1111/j.1469-0691.2006.01444.x.
  13. Sert M, Ozbek S, Paydas S, Yaman A. Is there any relationship between toxoplasma infection and reactive arthritis? J Postgrad Med 2007; 53(1):14-6. doi: 10.4103/0022-3859.30321.
  14. Khan AH, Noordin R. Serological and molecular rapid diagnostic tests for Toxoplasma infection in humans and animals. Eur J Clin Microbiol Infect Dis 2020; 39(1):19-30. doi: 10.1007/s10096-019-03680-2.
  15. Rostami-Nejad M, Cheraghipour K, Mojard E, Moradpour K, Razaghi M, Dabiri H. Seroprevalence and risk factors for Toxoplasma infection in a large cohort of pregnant women in Rural and Urban areas. HealthMED 2011; 5(2):354-59.
  16. Roozbehani M, Falak R, Mohammadi M, Hemphill A, Razmjou E, Meamar AR, et al. Characterization of a multi-epitope peptide with selective MHC-binding capabilities encapsulated in PLGA nanoparticles as a novel vaccine candidate against Toxoplasma gondii Vaccine 2018; 36(41):6124-32. doi: 10.1016/j.vaccine.2018.08.068.
  17. Molazadeh M, Karimzadeh H, Azizi MR. Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage. Iranian Journal of Reproductive Medicine 2014; 12(3):221-6.
  18. Sakkas LI, Bogdanos DP. Infections as a cause of autoimmune rheumatic diseases. Auto Immun Highlights 2016; 7(1):13. doi: 10.1007/s13317-016-0086-x.
  19. Balleari E, Cutolo M, Accardo S. Adult-onset Still's disease associated to toxoplasma gondii infection. Clin Rheumatol 1991; 10(3):326-7. doi: 10.1007/BF02208701.
  20. El-Sayed NM, Kishik SM, Fawzy RM. The current status of Toxoplasma gondii infection among Egyptian rheumatoid arthritis patients. Asian Pacific Journal of Tropical Disease 2016; 6(10):797-801. doi: 10.1016/S2222-1808(16)61133-7.
  21. Samarkos M, Vaiopoulos G. The role of infections in the pathogenesis of autoimmune diseases. Curr Drug Targets Inflamm Allergy 2005; 4(1):99-103. doi: 10.2174/1568010053622821.
  22. Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity–friends or foes? Trends Immunol 2009; 30(8):409-14. doi: 10.1016/
  23. Hosseininejad Z, Sharif M, Sarvi S, Amouei A, Hosseini SA, Chegeni TN, et al. Toxoplasmosis seroprevalence in rheumatoid arthritis patients: A systematic review and meta-analysis. PLoS Negl Trop Dis 2018; 12(6):e0006545. doi: 10.1371/journal.pntd.0006545.
  24. Kim H, Cho SK, Lee J, Bae SC, Sung YK. Increased risk of opportunistic infection in early rheumatoid arthritis. Int J Rheum Dis 2019; 22(7):1239-46. doi: 10.1111/1756-185X.13585.
  25. Fischer S, Agmon-Levin N, Shapira Y, Katz BS, Graell E, Cervera R, et al. Toxoplasma gondii: bystander or cofactor in rheumatoid arthritis. Immunol Res 2013; 56(2-3):287-92. doi: 10.1007/s12026-013-8402-2.
  26. Peng SL. Rheumatic manifestations of parasitic diseases. Semin Arthritis Rheum 2002; 31(4):228-47. doi: 10.1053/sarh.2002.30441.
  27. Shapira Y, Agmon-Levin N, Selmi C, Petríková J, Barzilai O, Ram M, et al. Prevalence of anti-toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun 2012; 39(1):112-6. doi: 10.1016/j.jaut.2012.01.001.
  28. Zandman-Goddard G, Shoenfeld Y. Parasitic infection and autoimmunity. Lupus 2009; 18(13):1144-8. doi: 10.1177/0961203309345735.
  29. Sultan BA, AL-Fatlawi SN, Abdul-Kadhim H, Obaid RF. Relationship between Toxoplasma gondii and autoimmune disease in aborted women in Najaf province. Karbala Jorunal of Medicine 2016; 9(1):2370-5.
  30. Bouratbine A, Siala E, Chahed MK, Aoun K, Ben RI. Sero-epidemiologic profile of toxoplasmosis in northern Tunisia. Parasite 2001; 8(1):61-6. doi: 10.1051/parasite/2001081061. [In French].
  31. El-Henawy AA, Hafez EAR, Nabih N, Shalaby NM, Mashaly M. Anti-Toxoplasma antibodies in Egyptian rheumatoid arthritis patients. Rheumatol Int 2017; 37(5):785-90. doi: 10.1007/s00296-017-3703-8.
  32. Salman YJ, Mohammed KA. Relationship between Toxoplasma gondii and arthritis among patients in Kirkuk city. Int J Curr Res Aca Rev 2015; 3(8):175-87.
  33. Tian AL, Gu YL, Zhou N, Cong W, Li GX, Elsheikha HM, et al. Seroprevalence of Toxoplasma gondii infection in arthritis patients in eastern China. Infectious Diseases of Poverty 2017; 6:153.
  34. Liesenfeld O. Oral infection of C57BL/6 mice with Toxoplasma gondii: a new model of inflammatory bowel disease? J Infect Dis 2002; 185(Suppl 1):S96-101. doi: 10.1086/338006.
  35. Lidar M, Langevitz P, Barzilai O, Ram M, Porat‐Katz BS, Bizzaro N, et al. Infectious serologies and autoantibodies in inflammatory bowel disease: insinuations at a true pathogenic role. Ann N Y Acad Sci 2009; 1173:640-8. doi: 10.1111/j.1749-6632.2009.04673.x.
  36. Garweg JG, de Kozak Y, Goldenberg B, Boehnke M. Anti-retinal autoantibodies in experimental ocular and systemic toxoplasmosis. Graefes Arch Clin Exp Ophthalmol 2010; 248(4):573-84. doi: 10.1007/s00417-009-1242-z.
  37. Dodangeh S, Daryani A, Sharif M, Aghayan SA, Pagheh AS, Sarvi S, et al. A systematic review on efficiency of microneme proteins to induce protective immunity against Toxoplasma gondii. Eur J Clin Microbiol Infect Dis 2019; 38(4):617-29. doi: 10.1007/s10096-018-03442-6.
  38. Gaffen SL. The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Curr Rheumatol Rep 2009; 11(5):365-70. doi: 10.1007/s11926-009-0052-y.
  39. Guiton R, Vasseur V, Charron S, Torres Arias M, Van Langendonck N, Buzoni-Gatel D, et al. Interleukin 17 receptor signaling is deleterious during Toxoplasma gondii infection in susceptible BL6 mice. J Infect Dis 2010; 202(3):427-35. doi: 10.1086/653738.
  40. Debierre-Grockiego F, Campos MA, Azzouz N, Schmidt J, Bieker U, Resende MG, et al. Activation of TLR2 and TLR4 by glycosylphosphatidylinositols derived from Toxoplasma gondii. Journal of Immunology 2007; 179(2):1129-37.
  41. Debierre-Grockiego F, Azzouz N, Schmidt J, Dubremetz JF, Geyer H, Geyer R, et al. Roles of glycosylphosphatidylinositols of Toxoplasma gondii induction of tumor necrosis factor-α production in macrophages. J Biol Chem 2003; 278(35):32987-93. doi: 10.1074/jbc.M304791200.
  42. Prandota J. Possible critical role of latent chronic Toxoplasma gondii infection in triggering, development and persistence of autoimmune diseases. International Journal of Neurology Research 2018; 4(1):379-463. doi: 10.17554/j.issn.2313-5611.2018.04.79.
  43. Al-Aubaidi IK, Al-Oqaily MA, Hamad SS. Role of Interleukin 33 During Infection with Toxoplasmosis in Rheumatoid Arthritis Patients. Indian Journal of Forensic Medicine & Toxicology 2020; 14(1):526-31. doi: 10.37506/ijfmt.v14i1.101.
  44. Falusi O, French AL, Seaberg EC, Tien PC, Watts DH, Minkoff H, et al. Prevalence and predictors of Toxoplasma seropositivity in women with and at risk for human immunodeficiency virus infection. Clin Infect Dis 2002; 35(11):1414-7. doi: 10.1086/344462.
  45. Wilking H, Thamm M, Stark K, Aebischer T, Seeber F. Prevalence, incidence estimations, and risk factors of Toxoplasma gondii infection in Germany: a representative, cross-sectional, serological study. Sci Rep 2016; 6:22551. doi: 10.1038/srep22551.