Novel And Unique Key Markers In The Inflammatory Pathways For Genital Tuberculosis (Gtb)

Panpalia, M.M. et al. 2020. NOVEL AND UNIQUE KEY MARKERS IN THE INFLAMMATORY PATHWAYS FOR GENITAL TUBERCULOSIS (GTB). Fertility and Sterility. Elsevier BV.

Objective
To identify novel and unique diagnostic markers for the presence of Genital Tuberculosis (GTB).

Design
Infertile women suspected of GTB were included in the study. An array of tests including endometrial biopsies for TB culture, nested TB-PCR, Immunocytochemistry, TNF alpha, P27, α1β3integrins and evaluation of CD138 and endoscopy including either laparoscopy and or hysteroscopy was carried out. Those confirmed with GTB by two or more parameters were considered as TB positive and those with either one or none of the parameters positive were considered to be TB negative. Expressional analysis was performed on the same sample of the endometrial biopsy that had been collected. Pathway analysis to establish markers associated with TB and integrated pathways differentially associated to normal physiology were mapped.

Materials and Methods
A total of 97 samples were subjected to diagnostic tests mentioned above. Results were tabulated to differentiate between TB positive and TB negative samples. Based on the screening tests, 34 samples were positive and 63 were negative. All these samples were subjected to custom designed gene expression analysis by microarray technique using Agilent G3 scanner and results were analysed on GeneSpring 14.9 software (Strand Lifescience). Data was normalized and those with fold chain more than 2 were considered for further analysis. Expression fold change of TB positive samples was compared to TB negative samples with respect to focused inflammatory pathway analysis comprising of 1052 genes. Through literature survey, a total of 1052 genes were identified as associated with inflammatory pathways and data of expression analysis was compared to these genes.

Results
Bioinformatics analysis of the study revealed that 129 genes were differentially regulated in TB positive endometrial tissue as compared to TB negative endometrial tissue. Further, expression of 47 genes was statistically significant and considered for further pathways and marker identification analysis. Results showed that apart from innate immune response pathways like MAPK and cytokine pathways, we observed that genes involved in cell migration, Adhesion-Extravasation, G-protein coupled receptor pathways were also altered in TB positive endometrium thus, explaining the associated infertility.

Conclusions
Early detection of GTB is important in salvaging reproductive potential. GTB has a detrimental impact on female fertility. However its diagnosis by conventional methods is at times difficult in this form of extra-pulmonary TB and delay in diagnosis can negatively impact on future fertility. The present study has identified novel markers in the form of differential expression of 52 genes involved not only in classical inflammatory response pathways but pathways associated with inflammatory dysfunction in GTB.

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