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THU0019 Features of telomere length distribution on individual chromosomes in rheumatoid arthritis
  1. M Barkovskaya1,
  2. A Bogomolov2,
  3. N Knauer1,
  4. E Blinova1,
  5. A Sizikov3,
  6. N Rubtsov2,
  7. V Kozlov1
  1. 1Laboratory of the Clinical Immunopathology, Research Institute of Fundamental and Clinical Immunology
  2. 2Laboratory of the Morphology and Function of Subcellular Components, Institute of Cytology and Genetics SB RAS
  3. 3Department of Clinical Rheumatology, Clinic of Immunopathology, Novosibirsk, Russian Federation

Abstract

Background Telomeres are nucleoprotein structures,that protect the ends of chromosomes during cell divisions [1,2,3]. Previously it was found, that average telomere length in immune cells is reduced in atopic and autoimmunity disorders.This fact indicates an early immune aging in immune-mediated diseases [4,5]. The distribution of telomere repeats on different chromosomes has an individual telomere profile in humans [6] and may be a congenital feature, that accelerates immunosenescence.

Objectives The purpose of this study was to evaluate the length of telomeres in the arms of individual chromosomes in patients with RA and healthy donors.

Methods The study included 6 patients with RA and 6 healthy donors (the median age 51.5 (50–54) and 51.5 (49–53) years respectively). Metaphase spreads obtained from PBMCs were used in this study. Written informed consent was obtained from each person enrolled in the study. At the time of sampling, RA inpatients characterized with acute exacerbation of the disease received treatment at the Clinic of Immunopathology,Novosibirsk. RA was diagnosed by clinicians according to ACR/EULAR 2010. For measurement of the telomere length on individual chromosome arms we used Q-FISH with (C3TA2)3 PNA-probe. Inverted DAPI banding was used for chromosome identification according to ISCN 2013. The new MeTeLen software was developed to estimate the telomere repeats relative quantity (http://www.bionet.nsc.ru/en/development/application-development/development-of-a-computer/metelen.html)in metaphase images.

Results When comparing the telomere length, it was found, that telomere on chromosome 16 p are shorter in patients with RA than in donors. Since each person has an individual telomere profile, we also analyzed the presence of shortened telomere sequences on individual chromosome arms relative to the average length of telomeres for each subject separately. As a result, patients with RA have a larger number of significantly shortened telomeres than donors (see Table).

Conclusions The revealed features of telomeric profiles of patients with RA may be an indication of a proliferative stress, that occurs as a result of the mass immune cell proliferation in the immunopathology. It can be assumed, that the presence of a great number of shortened telomeres can promote cell death through apoptosis. The observed shortening of the telomere length on chromosome 16 p in RA may be relevant in its pathogenesis. It is known, that telomere shortening can lead to increased gene expression near the telomere DNA region. Thus, in 16 p 13 a number of genes is localized, that are associated with RA or may be involved in its development.

References

  1. Olovnikov A.M, J. Theor. Biol. 41(1):181–190, 1973.

  2. Blackburn E.H., Gall J.G., J. Mol. Biol. 120:33–53, 1978.

  3. Hayflick L, Exp. Cell. Res. 37:614–636, 1965.

  4. Andrews N.P. et al., Gerontology 56(4):390–403, 2010.

  5. Dehbi A. ZA. Et al., Clin. Immunol. 9(12):1193–1204, 2013.

  6. Graakjaer J. et al., Mech. ageing dev., 124(5): 629–640, 2003.

References

Acknowledgements The study was funded by RSF (research project No 14–15–00346).

Disclosure of Interest None declared

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