There is increasing interest in exploring the link between Toxoplasma and Toxocara infections and autoimmune diseases. Recently, there has been a relationship between Toxoplasma gondii and Toxocara spp. infections and various autoimmune disorders, including rheumatoid arthritis but a clear relationship between toxoplasmosis and toxocariasis and JIA, has not been well documented. (3,4) .
The current study was conducted to estimate the seroprevalence of Toxocara and Toxoplasma in cases with juvenile idiopathic arthritis, its relation to the disease activity, and emphasize the importance of screening for both prior to immunosuppressive treatment.
The result of the current study showed a high prevalence of T. gondii infection among children with JIA (39.5%) compared to controls (16%) (P < 0.05) based on IgG seropositivity. However, the difference between cases and controls was statistically not significant as regard Toxocara IgG seropositivity (p = 0.27).
To our knowledge, there are no studies evaluating the seroprevalence of T.gondii in JIA patients are available to compare this data with. However, Toxoplasma gondii infection is progressively being reported in patients with arthritis in different Arab countries e.g., Tunisia (58.4%) (14), Iraq (54.0%) (15), and Egypt (54.0%) (16) and 76.7% (17), in Iran (18) ; and Europe (63.0%) (19).
The higher seroprevalence of anti-T. gondii IgG antibodies among JIA patients versus control patients which were reported in this work reflect an association between T. gondii infection and JIA.
The pathophysiology behind JIA disease is poorly understood. The significant association between toxoplasmosis and autoimmune diseases may be because T. gondii infection may act as a possible cofactor that triggers the development of autoimmune disease by different possible mechanisms (20).
T. gondii infection induced exhaustion of cytotoxic T lymphocyte and this will lead to losing their capacity to proliferate, cytokine production leads to the development of of different autoimmune (21).
Also, T. gondii infection initial innate immune response led by neutrophils. IL-17 is the major cytokine for neutrophil recruitment after infection and is a potent proinflammatory mediator involved in the pathogenesis of many autoimmune illnesses ( 22).
The increased prevalence of T. gondii infection in JIA children and adolescents may be also related to the disturbances in the immune system in JIA that attenuate adaptive cellular immunity, essential for controlling intracellular pathogens such as T. gondii. JIA is associated with alterations in the T cell repertoire, a decline in clonal expansion of naïve T cells in response to a previously unknown antigen, and a decline in newly generated naïve T cells which migrate from the thymus to the periphery (23).
JIA children and adolescents are exposed to multiple and often combined immunosuppressive drugs that promoted the reactivation of a latent Toxoplasma infection and may be predisposed to acquire novel infections (24).
In this work, there was an association between Immunosuppressive therapies and the frequency of T. gondii seropositivity in the studied participants. These results are in concordance with the results obtained (16, 25) who reported high prevalence of T. gondii among patients with different autoimmune diseases treated by immune-suppressive therapy.
Biological therapy plays a crucial role in improving the outcome of many patients with autoimmune diseases. However, this improvement has been associated with the risk of infection by opportunistic pathogens such as T. gondii (26).
The higher risk of T. gondii infection in JIA patients receiving biological therapy (especially TNF-α inhibitors) is because TNF-alpha is essential for granuloma formations, which are important in limiting the intracellular parasite’s growth (27); Anti-TNF agents used in JIA disease treatment will create an incline towards all kinds of infections, especially granulomatous disorders, including toxoplasmosis ( 28).
This study has demonstrated a significantly higher JADAS-27 among JIA children with T. gondii seropositive than seronegative cases (8.39 ± 1.64 vs. 4.65 ± 2.73; p = 0.02).
This association may be due to some toll-like receptors (TLRs) in mammals that had been identified, for which some pathogens act as ligands. Different immune responses can be induced due to binding between the TLRs and pathogens. According to the literature, T. gondii may be used as a ligand for TLRs, which can cause an inflammatory response. Therefore, this enhanced inflammatory response can cause increased disease activity (29).
Among the various clinical subtypes of JIA, seroprevalence rates showed no significant differences between seropositive and seronegative cases. However, the number of affected joints and duration of the disease is significantly higher among T. gondii IgG seropositive cases compared to seronegative cases (P < 0.05), and this may be related to increasing duration, creating an incline towards more adverse outcomes on the immune system and increase all kind of infections including T.gondii.