The investigation of levels of IgG and IgM autoantibodies against bacterial analog of HSP60, Tyrosyl-trna synthetase, and its separated domains in sera of women with uterine leiomyoma

M. Makarenko, R. Vorona, I. Sokol, V. Berestoviy, D. Govsieiev, A. Pogribna, A. Kornelyuk, M. Grom
Bogomolets National Medical University, Postgraduate Education Institute, Kуiv; Bogomolets National Medical University, Postgraduate Education Institute, Kуiv; Bogomolets National Medical University, Postgraduate Education Institute, Kуiv; Bogomolets National Medical University, Postgraduate Education Institute, Kуiv; Bogomolets National Medical University, Postgraduate Education Institute, Kуiv; Institute of Molecular Biology and Genetics NAS of Ukraine, Kyiv; Institute of Molecular Biology and Genetics NAS of Ukraine, Kyiv; Institute of Molecular Biology and Genetics NAS of Ukraine, Kyiv

Abstract


Uterine leiomyomas are common gynecologic tumor in reproductive-aged women. The molecular mechanisms behind the origin of leiomyomas are still relatively unknown. Tyrosyl-tRNA synthetase (TyrRS) and Hsp60 are housekeeping proteins that could be involved into different pathologies in various ways. The aim of the study was to investigate the levels of antibodies to Hsp60 and TyrRS and its distinct domains: mini-TyrRS and C-terminal domain in sera of patients with uterine leiomyoma (UL). Materials and methods: Specific IgG and IgM autoantibodies in sera of 25 women with UL before therapy and 5 healthy subjects were measured by ELISA. The specificity of the reaction of IgG autoantibodies against the Hsp60 and mini-TyrRS proteins was checked using a western blot assay. Statistical analysis was performed using the STATISTICA 10.0 software. (StatSoft, USA). Non-parametric data were compared in the Mann-Whitney U-test. Results: The elevated levels of IgM autoantibodies against all the proteins studied occur frequently neither in control nor in experimental cohort. In the group of healthy donors, individuals with elevated levels of IgG autoantibodies against any of the proteins studied were not detected. Meanwhile 19 of 25 (76 %) and 18 of 25 (72 %) women with UL had significantly increased serum levels of autoantibodies to mini-TyrRS and Hsp60 respectively. Intriguingly, 17 of 25 samples from women with uterine fibroids (68 %) were positive against mini-TyrRS and Hsp60 analog simultaneously. The levels of autoantibodies to mini-TyrRS in sera of women with UL were 1.7 times higher than in sera of healthy donors, for Hsp60 the corresponding index was 2.1. Increasing levels of autoantibodies against each
of the two proteins was statistically significant with a degree of reliability of p <0.01. The data obtained by ELISA were confirmed by western-blot analysis for Hsp60 but not for mini-TyrRS. Conclusion: We propose that elevated levels of autoantibodies to Hsp60 and mini-TyrRS in sera of persons with UL may serve as element of panel of protein markers for monitoring of pathology.


Keywords


Hsp60, TyrRS, uterine leiomyoma, autoantibodies

Full Text:

PDF>PDF

References


Cappello F., Marino Gammazza A., Palumbo Piccionello A., Campanella C., Pace A., Conway de Macario E., Macario A. Hsp60 chaperonopathies and chaperonotherapy: targets and agents. Expert Opin. Ther Targets. 2014;18(2):185-208.

Caruso Bavisotto C., Cappello F., Macario A., Conway de Macario E., Logozzi M., Fais S., Campanella C. Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment. Expert Review of Molecular Diagnostics. 2017;17(9):815-22.

Ciarmela P., Bloise E., Gray P., Carrarelli P., Islam M., De Pascalis F., Severi F., Vale W., Castellucci M., Petraglia F. Activin-A and myostatin response and steroid regulation in human myometrium: disruption of their signaling in uterine fibroid. J Clin Endocrinol Metab. 2011;96(3):755–765.

Deniset J., Pierce G. Heat Shock Proteins: Mediators of Atherosclerotic Development. Curr Drug Targets. 2015;16(8):816-26.

Dvorská D., Braný D., Danková Z., Halašová E., Višňovský J. Molecular and clinical attributes of uterine leiomyomas. Tumor Biology. 2017;39:1–16.

Greenberg Y., King M., Kiosses W., Ewalt K., Yang X., Schimmel P., Reader J., Tzima E. The novel fragment of tyrosyl-tRNA synthetase, mini-TyrRS, is secreted to induce an angiogenic response in endothelial cells. FASEB J. 2008;22(5):1597–605.

Grom M., Yakovenko L., Sidorik L., Kornelyuk A., Grygorenko V., Vikarchuk M. [Tyrosyl-tRNA synthetase and its separated domains are suppositional components of prostate cancer pathogenesis]. Bulletin of Taras Shevchenko National University of Kyiv. Series: Problems of Physiological Functions Regulation. 2016;1(20):38-44.

Grom M., Yakovenko L., Granich V., Dobrohod A., Torbas O., Radchenko G., Sirenko Yu., Sidorik L., Kornelyuk A. Autoantibodies againsttyrosyl-tRNA synthetase and its separated domains at essential hypertension. Biopolym and Cell. 2015;31(4):255–63.

Kapustian L., Kyyamova R., Gryshkova V., Terentiev A., Filonenko V., Sidorik L. Obtaining recombinant chaperon GroEL and its immunological cross-reactivity with Hsp60. Biopolymers and cell. 2006; 22(2):117-120.

Levy G., Hill M., Plowden T., Catherino W., Armstrong A. Biomarkers in uterine leiomyoma. FertilSteril. 2013;99(4):1146–52.

Lianos G., Alexiou G., Mangano A., Mangano A., Rausei S., Boni L., Dionigi G., Roukos D. The role of heat shock proteins in cancer. Cancer Lett. 2015;360(2):114-8.

Wakasugi K., Schimmel P. Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science. 1999;284:147–151.

Yakovenko L., Smalyuk Yu., Kapustian L., Chornyi S., Pogribna A., Granich V., Dobrohod A., Torbas O., Radchenko G., Sirenko Yu., Sidorik L. [Anti-Hsp60 antibodies in patients with arterial hypertension and persons with complicated heredity for hypertension]. Medical case. 2015;3-4:43-52.

Yao P., Fox P. Aminoacyl-tRNA synthetases in medicine and disease. EMBO Mol Med. 2013;5(3):332-43.

Yokota Sh., Hirata D., Minota S., Higashiyama T., Kurimoto M., Yanagi H., Yura T., Kubota H. Autoantibodies against chaperonin CCT in human sera with rheumatic autoimmune diseases: comparison with antibodies against other Hsp60 family proteins. Cell Stress & Chaperones.

;5(4):37–46.

Zhou X., Xue L., Hao L., Liu Sh., Zhou F., Xiong H., Qi X., Lin D., Shao Sh. Proteomics-based identification of tumor-relevant proteins in lung adenocarcinoma. Biomed Pharmacother. 2013;67(7):621-7.

***

Received: 19.03.2018

Revised: 23.04.2018

Signed for publication: 23.04.2018




DOI: http://dx.doi.org/10.17721/2616_6410.2018.24.12-17

Refbacks

  • There are currently no refbacks.


Лицензия Creative Commons
This journal is available according to the Creative Commons License «Attribution» («Атрибуція») 4.0 Global (CC-BY).