Interleukins IL33/ST2 and IL1-β in Intrauterine Growth Restriction and Seropositivity of Anti- Toxoplasma gondii Antibodies

Abstract

Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis. It may produce severe damage in immunocompromised individuals, as well as congenital infection and intrauterine growth restriction (IUGR). Previous reports have associated interleukin IL-33 with miscarriage, fetal damage, and premature delivery due to infections with various microorganisms. However, IL-33 has not been associated with congenital toxoplasmosis. The sST2 receptor has been reported in patients who have had recurrent miscarriages. On the other hand, IL-1β was not found in acute Toxoplasma infection. Our aim was to analyze the associations between the serum levels of IL-33 and IL-1β in IUGR and toxoplasmosis during pregnancy. Eighty-four serum samples from pregnant women who had undergone 26 weeks of gestation were grouped as follows: with anti-Toxoplasma antibodies, without anti-Toxoplasma antibodies, IUGR, and the control group. IgG and IgM anti-T. gondii antibodies, as well as IL-33, ST2, and IL-1β, were determined using an ELISA assay. Statistical analyses were performed using the Pearson and Chi-square correlation coefficients, as well as the risk factors and Odds Ratios (ORs), with a confidence interval of 95% (CI 95). The results showed that 15/84 (17.8%) of cases were positive for IgG anti-Toxoplasma antibodies and 2/84 (2.38%) of cases were positive for IgM. A statistically significant difference was found between IUGR and IL-33 (p < 0.001), as well as between ST2 and IUGR (p < 0.001). In conclusion, IUGR was significantly associated with IL-33 and ST2 positivity based on the overall IUGR grade. No significant association was found between IUGR and the presence of anti-Toxoplasma antibodies. There was no association between IL-1β and IUGR. More research is needed to strengthen the utility of IL-33 and ST2 as biomarkers of IUGR.

Keywords: IL-1β; IL-33; intrauterine growth restriction; toxoplasmosis.

Figure 1

The immune response to Toxoplasma gondii and the possible intervention of IL-33 is shown. Toxoplasma gondii (T. gondii), Pathogen-Associated Molecular Patterns (PAMPs), Toll-like receptors (TLR), interleukin 12 (IL-12), interleukin 2 (IL-2), interleukin 1 beta (IL-1β), gamma interferon (IFNγ), immunoglobulin G (IgG), immunoglobulin M (IgM), helper T cells (Th), interleukin 10 (IL-10), interleukin 4 (IL-4), cytotoxic T lymphocytes (Tc), dendritic cells (DC), natural killer cells (NK), interleukin 33 (IL-33), major histocompatibility complex (MHC), cluster of differentiation 4 positive (CD4+), cluster of differentiation 8 positive (CD8+), and innate lymphoid cells (ILC 1).

Figure 2

Anti-T. gondii antibody concentrations: the IgG and IgM antibodies of each group. Group I: positive IUGR and Toxoplasma antibodies (orange color), Group II: positive IUGR and negative for T. gondii antibodies (brown color); and Group III: negative for T. gondii and IUGR (green color), purple line is the cutoff value.

Figure 3

Concentrations of interleukins IL-33, IL-1β, and ST2 in the different groups. Group I: IUGR+ anti-Toxoplasma IgG antibodies positive (AbTg+) (orange color n = 16); Group II: IUGR+ anti-Toxoplasma antibodies negatives (AbTg−) (brown color n = 19); and Group III: AbTg−IUGR− (green color n = 49) Regarding IL-33. Increased values were observed predominantly in Group II (C).

Figure 4

The IL-33, IL-1β, and ST2 concentrations among groups were compared using ANOVA. The IL-33 positivity values of the groups with IUGR were statistically significant (p < 0.05, p < 0.001). For IL-1β, a statistical significance of p < 0.001, p < 0.001 arose during the comparison of the positivity of Group I (Ab anti-Tg+/IUGR+). For ST2 a statistical significance of p < 0.001, p < 0.0001 with that of the control group.

Figure 5

Mean concentrations interleukins by group, Anti-T. gondii antibodies+/IUGR+, Anti-T. gondii-/IUGR+ and control group.