Immunological Markers of Chlamydia trachomatis Infection in Epithelial Ovarian Cancer.

BACKGROUND/AIM: Pelvic inflammatory disease (PID) is a risk factor for epithelial ovarian cancer (EOC). Chlamydia trachomatis infection, a major cause of PID, may persist in some women. Serum IgG antibodies to chlamydial TroA and HtrA are more common in ascending or repeat chlamydial infection than in uncomplicated infection. The aim of this study was to explore the role of C. trachomatis infection in EOC by analyzing chlamydial TroA, HtrA and major outer membrane protein (MOMP) IgG serum antibody responses. PATIENTS AND METHODS: The study is based on the review of Oulu University Hospital medical records of 162 women diagnosed with EOC between March 2008 and May 2018. Serum IgG antibody responses to recombinant C. trachomatis TroA, HtrA and MOMP were analyzed using enzyme-linked immunoassay. Complete response to the first line therapy and the three-year survival were the study endpoints. RESULTS: Altogether, 16.7%, 11.1% and 12.3% women were C. trachomatis TroA, HtrA and MOMP IgG positive, respectively. Women with these antibodies were more likely to have a complete response to the first-line treatment, compared to women without these antibodies (63.0% vs. 34.1% for TroA IgG, 50.0% vs. 37.5% for HtrA IgG and 50% vs. 37.3% for MOMP IgG, respectively). The presence of these antibodies predicted better three-year survival. CONCLUSION: Women with EOC and positive markers of persistent C. trachomatis infection have better response to the first-line treatment and seem to have better three-year survival.

Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I.

Collagen prolyl 4-hydroxylases (C-P4H-I, C-P4H-II, and C-P4H-III) catalyze formation of 4-hydroxyproline residues required to form triple-helical collagen molecules. Vertebrate C-P4Hs are α2ß2 tetramers differing in their catalytic α subunits. C-P4H-I is the major isoenzyme in most cells, and inactivation of its catalytic subunit (P4ha1(-/-)) leads to embryonic lethality in mouse, whereas P4ha1(+/-) mice have no abnormalities. To study the role of C-P4H-II, which predominates in chondrocytes, we generated P4ha2(-/-) mice. Surprisingly, they had no apparent phenotypic abnormalities. To assess possible functional complementarity, we established P4ha1(+/-);P4ha2(-/-) mice. They were smaller than their littermates, had moderate chondrodysplasia, and developed kyphosis. A transient inner cell death phenotype was detected in their developing growth plates. The columnar arrangement of proliferative chondrocytes was impaired, the amount of 4-hydroxyproline and the Tm of collagen II were reduced, and the extracellular matrix was softer in the growth plates of newborn P4ha1(+/-);P4ha2(-/-) mice. No signs of uncompensated ER stress were detected in the mutant growth plate chondrocytes. Some of these defects were also found in P4ha2(-/-) mice, although in a much milder form. Our data show that C-P4H-I can to a large extent compensate for the lack of C-P4H-II in proper endochondral bone development, but their combined partial and complete inactivation, respectively, leads to biomechanically impaired extracellular matrix, moderate chondrodysplasia, and kyphosis. Our mouse data suggest that inactivating mutations in human P4HA2 are not likely to lead to skeletal disorders, and a simultaneous decrease in P4HA1 function would most probably be required to generate such a disease phenotype.