Hypothesis about the protective role of ccr5delta32 mutations in juvenile idiopathic arthritis: fiction or reality?

  • Authors: Fedorova E.V.1, Egorov A.S.1, Ammosova T.2, Avrusin S.L.1, Santimov A.V.1, Kostik M.M.1, Dubko M.F.1, Kalashnikova O.V.1, Masalova V.V.1, Likhacheva T.S.1, Snegireva L.S.1, Grom A.A.3, Nekhai S.2, Chasnyk V.G.1
  • Affiliations:
    1. Saint Petersburg State Pediatric Medical University
    2. Howard University
    3. Cincinnati Children’s Hospital Medical Center
  • Issue: Vol 5, No 4 (2014)
  • Pages: 53-59
  • Section: Articles
  • URL: https://journals.eco-vector.com/pediatr/article/view/1164
  • DOI: https://doi.org/10.17816/PED5453-59
  • Cite item

Abstract


It is suspected that the prevalence in different ethnic groups of HLA-genotype and of mutation CCR5delta32 - factors which alter adhesion of protein CCR5 - are the causes of different prevalence of juvenile idiopathic arthritis in different ethnic populations. Prerequisites to the fact that the mutation CCR5delta32 may have importance in determining susceptibility to the disease were the observations showing that CCR5 deletion polymorphism reveals a population and geographic diversity in addition to ethnic specificity. But reports on the role of gene deletion in the CCR5 chemokine receptor susceptibility to JIA rather contradictory. 234 DNA samples of patients with systemic JIA (soJIA) were ana-lyzed. The diagnosis was made according to the ILAR criteria. DNA was isolated using QIAamp Mini Kit (QIAGEN) according to the protocol provided. Our results didn’t reveal any differences in prevalence of mutation in patients with soJIA, in patients with soJIA + macrophage activation syndrome and in total population. Our results do not support the idea of protective role of the muta-tion CCR5delta32 against soJIA, which conclusion can be explained also by probable association of soJIA with HLA-genotype or other factors of ethnicity. At the same time, it can be considered as an additional evidence of expediency of soJIA being an original disease different from the rest of JIA group of diseases.

Full Text

Restricted Access

About the authors

Elena Vladimirovna Fedorova

Saint Petersburg State Pediatric Medical University

Email: detymedic@mail.ru
MD, Research Fellow, Chair of Hospital Pediatrics

Andrey Sergeyevich Egorov

Saint Petersburg State Pediatric Medical University

Email: egorov.doc@gmail.com
MD, Research Fellow, Chair of Hospital Pediatrics

Tatyana Ammosova

Howard University

Email: tatiana.ammosova@howard.edu
PhD, Assistant Research Professor

Sergey Lvovich Avrusin

Saint Petersburg State Pediatric Medical University

Email: avrusin4@gmail.com
MD, PhD, Associate Professor, Chair of Hospital Pediatrics

Andrey Vyacheslavovich Santimov

Saint Petersburg State Pediatric Medical University

Email: a.santimoff@gmail.com
MD, Research Fellow, Chair of Hospital Pediatrics

Mikhail Mikhaylovich Kostik

Saint Petersburg State Pediatric Medical University

Email: mikhail.kostik@gmail.com
MD, PhD, Associate Professor, Chair of Hospital Pediatrics

Margarita Fedorovna Dubko

Saint Petersburg State Pediatric Medical University

Email: andrq@rambler.ru
MD, PhD, Associate Professor, Chair of Hospital Pediatrics

Olga Valeryevna Kalashnikova

Saint Petersburg State Pediatric Medical University

Email: koira7@yandex.ru
MD, PhD, Associate Professor, Chair of Hospital Pediatrics

Vera Vasilyevna Masalova

Saint Petersburg State Pediatric Medical University

Email: masalova.vera@gmail.com
MD, Research Fellow, Chair of Hospital Pediatrics

Tatyana Serafimovna Likhacheva

Saint Petersburg State Pediatric Medical University

Email: tatianasl@list.ru
MD, Research Fellow, Chair of Hospital Pediatrics

Ludmila Stepanovna Snegireva

Saint Petersburg State Pediatric Medical University

Email: l.s.snegireva@mail.ru
MD, Department of Pediatrics N 3

Alexey Alekseevich Grom

Cincinnati Children’s Hospital Medical Center

Email: Alexei.grom@cchmc.org
MD, PhD, Dr Med Sci, Professor, Department of Pediatrics

Sergei Nekhai

Howard University

Email: snekhai@howard.edu
Ph.D., Director, RCMI Proteomics Core Facility, Associate Professor, Center for Sickle Cell Disease

Vyacheslav Grigoryevich Chasnyk

Saint Petersburg State Pediatric Medical University

Email: chasnyk@gmail.com
MD, PhD, Dr Med Sci, Professor, Head of the Department of Hospital Pediatrics

References

  1. Cohn S. K., Weaver J. R., Weaver L. T. The Black Death and AIDS: CCR5-_32in genetics and history. J. Med. 2006; 99: 497-503.
  2. Hinks A., Martin P., Flynn E. Association of the CCR5 gene with juvenile idiopathic arthritis. Genes and Immunity. 2010; 11: 584-89.
  3. Hinks A., Martin P., Flynn E. Childhood Arthritis Prospective Study (CAPS). Association of the CCR5 gene with juvenile idiopathic arthritis. Genes Immun. 2010; 11 (7): 584-89.
  4. Lindner E., Nordang G. B., Melun E. Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis. BMC Med Genet. 2007: 8-33.
  5. Novembre J., Galvani A. P., Slatkin M. The Geographic Spread of the CCR5 D32 HIV-Resistance Allele. PLoS Biology. 2005; 3: 339.
  6. Ødum N., Bregenholt S., Eriksen K. W. The CC-chemokine receptor 5 (CCR5)is a marker of, but not essential for the development of human Th1. Tissue Antigens. 1999; 54: 572-77.
  7. Pokorny V., McQueen F., Yeoman S. Evidence for negative association of the chemokine receptor CCR5 d32 polymorphism with rheumatoid arthritis. Ann Rheum. 2005;64: 487-90.
  8. Prahalad S. Negative association between the chemokine receptor CCR5-Δ32 polymorphism and rheumatoid arthritis: A meta-analysis. Genes Immun. 2006; 7 (3): 264-68.
  9. Prahalad S., Bohnsack J. F., Jorde L. B. Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arthritis. Genes Immun. 2006; 7 (6): 468-75.
  10. Prakken B., Albani S., Martini A. Juvenile idiopathic arthritis. Lancet. 2011 Jun 18; 377 (9783): 2138-49.
  11. Ramanan A. V., Grom A. A. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology. 2005; 44: 1350-1353.
  12. Ravelli A., Martini A. Juvenile idiopathic arthritis. Lancet, 2007: 767-78.
  13. Scheibel I., Veit T., Neves A. G., Souza L., Prezzi S., Machado S., Kohem C., Icarelli M., Xavier R., Brenol J. C., Chies J. A. Differential CCR5Delta32 allelic frequencies in juvenile idiopathic arthritis subtypes: evidence for different regulatory roles of CCR5 in rheumatological diseases. Scand J Rheumatol. 2008; 37 (1): 13-7.
  14. Seisdedos F. A., Parmentier M. Genetics of resistance to HIV infection: Role of co-receptors and co-receptor ligands. Seminars in Immunology. 2006; 18: 387-403.
  15. Sikora et al. Markedly Low-Level of Interferon-Induced Gene Expression Distinguishes Active Systemic Juvenile Idiopathic Arthritis Synovium From other JIA subtypes. Arthritis Rheum 2012; 64: 3799-808.

Statistics

Views

Abstract - 1800

PDF (Russian) - 290

Cited-By


PlumX


Copyright (c) 2014 Fedorova E.V., Egorov A.S., Ammosova T., Avrusin S.L., Santimov A.V., Kostik M.M., Dubko M.F., Kalashnikova O.V., Masalova V.V., Likhacheva T.S., Snegireva L.S., Grom A.A., Nekhai S., Chasnyk V.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies