Elevated seropositivity of Toxoplasma gondii IgG in rheumatoid arthritis patients in Diyala Province, Iraq

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Introduction

As an obligate protozoan with a global distribution, Toxoplasma gondii is responsible for the zoonotic disease toxoplasmosis and takes humans and a wide-range of animals as intermediate hosts while felids act as definitive hosts [7, 18, 19, 21]. Toxoplasmosis can be transmitted sexually (through unprotected sex, as the parasite can be present in seminal fluid), potentially leading to serious outcomes like congenital toxoplasmosis in a pregnant woman’s foetus. However, sexual transmission is not the most common route, which includes ingesting contaminated undercooked meat, organ transplantation, blood transfusion, unwashed vegetables, or contact with cat feces [5, 7, 11].

Emerging evidence suggests a link between toxoplasmosis and autoimmune disorders [6, 10]. Moreover, toxoplasmosis has been implicated in various complications, including congenital hearing loss [14, 17, 23]. Recent research by our group has linked the parasite to chronic health conditions such as diabetes and cancer, further highlighting its clinical significance [18, 19, 20].

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation, causing pain and disability [12], with a prevalence of about 1% globally [3, 13].

The association between Toxoplasma gondii infection and rheumatoid arthritis (RA) has received increasing attention [13]. Accumulating evidence suggests that T. gondii infection may be associated with RA through multiple immunological mechanisms, including chronic immune stimulation, pro-inflammatory cytokine imbalance, molecular mimicry, and impaired immune regulation [10, 13]. The present study aimed to evaluate the seroprevalence of toxoplasmosis in Iraqi RA subjects in comparison with apparently healthy controls living in Diyala Province, middle of Iraq.

Materials and methods

Study design and serological testing. One hundred patients clinically diagnosed with rheumatoid arthritis (RA) and 100 healthy volunteers, aged 20–79 years were involved in this study. RA patients were recruited from the Rheumatology Clinic at Baquba Teaching Hospital. The seropositivity of IgG and IgM was determined by ELISA kit (Acon, USA) and as described previously [18].

Participants were anonymized using unique ID codes. Demographic data and risk factors for toxoplasmosis were collected using structured questionnaires. The scientific and ethic committee (Diyala University) approved the study protocol (Protocol 3/2023).

Statistical analysis. A chi-square test was used to determine if there is a significant association between the different sociodemographic characteristics. In order to compare between the seropositive and seronegative subjects, Independent (Unpaired) T-test was used.

Results

The results showed a significant difference (p = 0.0363) in Toxoplasma gondii IgG seropositivity between rheumatoid arthritis (RA) subjects (40.0%) in comparison with healthy individuals (26.0%) in Diyala Province (Table 1). No participant in either group tested positive for IgM antibodies, indicating the presence of chronic rather than recent infections (Table 1). The present study found an odds ratio of 1.9 for toxoplasmosis in Iraqi RA patients in comparison with control subjects, which means RA patients are nearly 2 times more likely to have toxoplasmosis in comparison with healthy subjects (Table 1).

 

Table 1. IgG and IgM seropositivity in rheumatoid arthritis subjects patients compared to controls

Groups	No. tested	No. positive		% seropositivity
		IgG	IgM	IgG	IgM
Arthritis group	100	40	0.0	40	0.0
Control group	100	26	0.0	26	0.0
Odds ratio				1.9
P-value				p = 0.0363

 

Regarding age distribution (Table 2), the highest seropositivity rate among RA patients (50.0%) was observed in the 20–39-year age group. In comparison, control subjects in the same age range showed a lower rate of 17.1%, with borderline statistical significance (p = 0.0599). The calculated odds ratio for toxoplasmosis was 4.8, indicating that RA patients within this age group are approximately 4.8 times more likely to be seropositive than their control counterparts (Table 2).

 

Table 2. Seroprevalence of Toxoplasma gondii IgG in rheumatoid arthritis subjects compared to controls

Age (years)	Seroprevalence of T. gondii IgG				Odds ratio	p-value
	Arthritis subjects		Controls
	No. tested	No. positive (%)	No. tested	No. positive (%)
20–39	8	4 (50.0)	35	6 (17.1)	4.8	0.0599
40–49	35	14 (40.0)	32	10 (31.2)	1.47	0.4565
50–59	34	13 (38.2)	23	6 (26.0)	1.75	0.3423
60–69	23	9 (39.1)	10	4 (40.0)	0.96	0.9625

 

As shown in Table 3, seroprevalence among males with RA was significantly higher (48.0%) than in healthy males (22.0%) (p = 0.0075). Among females, the difference in seropositivity was not significant. In addition, residence (rural vs urban) did not significantly influence seropositivity in either group.

 

Table 3. Seroprevalence of Toxoplasma gondii IgG in rheumatoid arthritis subjects compared to controls according to the gender and residency

Variables	Seroprevalence of T. gondii IgG				Odds ratio	p-value
	Arthritis subjects		Controls
Gender	NT*	NP* (%)	NT*	NP* (%)
Males	50	24 (48.0)	50	11 (22.0)	3.3	0.0075
Females	50	16 (32.0)	50	15 (30.0)	1.1	0.8288
Residency	NT*	NP* (%)	NT*	NP* (%)
Rural	46	19 (41.3)	45	11 (26.0)	2.2	0.0899
Urban	54	21 (38.8)	55	15 (27.2)	1.7	0.1991

Note. *NP: number positive; NT: number tested.

 

Discussion

This study revealed a significant difference in Toxoplasma gondii IgG seropositivity between rheumatoid arthritis (RA) subjects (40.0%) in comparison with healthy individuals (26.0%) in Diyala Province. This supports findings from other regions of Iraq. For instance, Al-Kalaby et al. [1] reported 82.1% IgG seropositivity in arthritic women in Najaf, suggesting a potential immunomodulatory role of T. gondii in autoimmune diseases. In Baghdad, Kuba et al. [11] reported that 36.0% of Iraqi RA patients showed T. gondii IgG seropositivity in comparison with 12% in control healthy subjects. In another study, Al-Oqaily and Al-Ubaidi [2] found IgG seropositivity rate of 36.8% among RA patients.

Internationally, studies from Egypt and China also support this association. El-Sayed et al. [9] reported 54% IgG positivity in Egyptian RA patients, while Tian et al. [22] found higher prevalence in Chinese RA patients (18.8%) compared to healthy controls (12.0%). Hosseininejad et al. [13] reported that the prevalence of toxoplasmosis in the RA patients was 46.0%, while it was 21.0% in the control subjects, and the difference was highly significant. Our results align with these studies and reinforce the notion that chronic toxoplasmosis may be linked with the pathogenesis or exacerbation of RA.

The present study found an odds ratio (OR) of 1.9 for toxoplasmosis in Iraqi RA patients in comparison with control subjects, which means RA patients are nearly 2 times more likely to have toxoplasmosis. This OR is lower than that recorded in the studies conducted in Iraq [1, 16] which were 3.7 and 4.4, respectively. A meta-analysis found an odds ratio of 3.3 for toxoplasmosis in RA patients compared to controls, which means RA patients are 3.3 times more likely to have toxoplasmosis [13]. These differences could be due to differences in virulence of parasitic strains and host response [13, 18].

Notably, no participant in either group tested positive for IgM antibodies, indicating the presence of chronic rather than recent infections. Similarly, none of the Egyptian arthritic subjects tested positive for these antibodies [8].

Gender was not a major factor influencing infection rates, consistent with previous findings [1, 22]. Socioeconomic and immunological variables, including immune suppression and drug therapies used in RA, may increase susceptibility to chronic parasitic infections [4, 15]. Given the immune alterations in RA — particularly T-cell dysfunction, patients may be more prone to parasitic disease such as toxoplasmosis [4]. Whether T. gondii contributes to the onset of RA or is a consequence of immune dysregulation remains to be clarified.

A limitation of this study is the absence of an analysis examining the relationship between Toxoplasma gondii serological status and the clinical and laboratory characteristics of RA. Such an analysis would help determine whether persistent T. gondii infection influences the clinical phenotype and disease severity of RA, which is essential for understanding the biological significance of this association.

Conclusion

This study reinforces the evidence supporting a link between chronic T. gondii infection and rheumatoid arthritis. These findings highlight the need for increased awareness, targeted screening, and appropriate management strategies to protect vulnerable populations from the complications of toxoplasmosis.

About the authors

M.H. Ismail

Diyala University

Email: masarhadi333@gmail.com

PhD, Lecturer, Department of Biology, College of Sciences

Iraq, Diyala

Abdul-Lateef Molan

Diyala University

Author for correspondence.
Email: molanal99@gmail.com

PhD, Professor, Department of Biotechnology, College of Sciences

Iraq, Diyala

References

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