Possible cellular expression of IFN-γ and IFN- γ R1 (CD119) in aborted women infected with Toxoplasma gondii

number: 
1568
English
Degree: 
Imprint: 
Medicine
Author: 
Raghad Bennai Al-Fertosi
Supervisor: 
Dr. Ameena S.M.Juma
year: 
2006

Abstract:

Toxoplasma gondii infects a large number of people worldwide but seldom causes significant medical problems, except in immunocompromised individuals and during pregnancy. Toxoplasma infection may lead to abortion and the exact mechanisms of abortion are still unknown. Aberrant type 1 cytokines production, IFN-γ and IFN-γR1 (CD119) have been suggested to be related to the frequency of abortion caused by T. gondii infection. Therefore, the present study was conducted to investigate the possible role of the IFN-γ, IFN-γR1, and IFN-γR1/IFN-γ ratio in inducing abortion in T. gondii infected women. This study was designed based on one hundred and twenty six women with abortion includes 6 women with induced abortion. Venous blood was collected from these women, and serum was obtained for the performance of the ELISA test for the detection of anti-Toxoplasma IgM to indicate acute infection. Paraffin embedded blocks of the trophoblastic tissue obtained from each patient were prepared. These blocks were investigated for the presence of T. gondii antigen by using immunohistochemical analysis, using specific monoclonal antibody for T. gondii. According to the immunohistochemical analysis, the patients were divided into three groups, group 1: 26 positive for Toxoplasma, group 2: 26 negative for Tosoplasma, and group 3: 6 negative for Toxoplasma (induced abortion group). The results indicated a high frequency of the T. gondii infection among women with abortion, 23 of 120 women (19.17%) have IgM Abs against T. gondii by ELISA test. The use of ELISA test for the detection of anti-Toxoplasma IgM was highly specific (100%) but not highly sensitive (88.46%). This could explain the use of more sensitive techniques for the detection of T. gondii infection like immunohistochemical analysis. The results of the IHC revealed that 26 of 120 women (21.66%) have Toxoplasma antigen within the trophoblastic tissue. The sensitivity and specificity of IHC were 100%, 96.91%, respectively. In this protocol, the majority of patients within the positive and negative groups were found to have no previous abortions, while patients with previous abortions constituted a less percent. Among the induced abortion group, it has been found that all the six cases had no previous abortions. The majority of abortion cases within the positive group for T. gondii fall in the period of 12 weeks (41%) followed by 8 (15%) and 10 (12%) weeks of gestational age. Levels of IFN-γ and IFN-γR1 were investigated by using immunohistochemical analysis. The results revealed a highly significant difference (P<0.01) regarding the mean percent of IFN-γ and IFN-γR1 when compared between the positive and negative groups, while there was no such significant difference (P>0.05) regarding the mean percent of IFN-γR1/ IFN-γ ratio between positive and negative groups. In this work, t-test revealed a highly significant difference (P<0.001) regarding the mean percent of IFN-γ and IFN-γR1 and a significant difference (P<0.05) regarding the mean percent of IFN-γR1/ IFN-γ ratio between positive and induced abortion groups. Similarly, a highly significant difference was found when the mean percent of IFN-γ and IFN-γR1 were compared between the negative and induced abortion groups. The results of immunohistochemical analysis of IFN-γ, IFN-γR1 and IFN-γR1/IFN-γ ratio within the positive group showed that there were negative and highly significant correlations (r =-0.919, p<0.001; r=-0.575, p<0.001; r =-0.897, p<0.001, respectively) with gestational age but not with number of previous abortions. Moreover, the correlation of IFN-γR1 and IFN-γR1/ IFN-γ ratio with IFN-γ were positive and highly significant (r =0.673, p<0.001; r =0.950, p<0.001, respectively). Similarly, the correlation of IFN-γR1/ IFN-γ ratio with IFN-γR1 was a positive significant one (r =0.412, p<0.05).
Finally, the results of immunohistochemical analysis revealed higher levels of IFN-γ and IFN-γ R1 in the positive group when compared to the negative and induced abortion groups. In addition, the ratio of IFN-γ R1 to IFN-γ was 1.2:1 in the positive group and 1.28:1 in the negative group, while in the induced abortion group was 2:1. In conclusion, the data of this study strengthen the possibility that IFN-γ and IFN-γR1 may explain the role of type 1 cytokines in the pathogenesis of abortion in the positive group for T.gondii and in the transmission of the parasite from the mother to the fetus by the presence of IFN-γ R1 on the trophoblastic cells.