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Association of biomarkers of inflammation and HLA-DRB1 gene locus with risk of developing rheumatoid arthritis in females

Rheumatology International volume 39, pages 2147–2157 (2019)Cite this article

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease causing chronic inflammation of the joints. Multiple factors, including HLA-DRB1 gene variants, influence the susceptibility to RA. The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. In this study, we compared the inflammatory biomarkers values, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), between patients with RA and healthy control group of females of the Public Institution Health Centre of Sarajevo Canton. In addition, we estimated the frequencies of the HLA-DRB1 gene variants and their association with the risk for RA development in females. The haematological and biochemical tests were completed on automated analyzers. To assess the association between the HLA-DRB genes and the risk of RA in females, low-resolution genotyping of the HLA-DRB1, DRB3, DRB4, and DRB5 gene loci was performed by the sequence-specific polymerase chain reaction method (PCR-SSP). ESR and CRP were the most sensitive acute-phase reactants in females with RA and there was a correlation between ESR and CRP values in RA patients. There was significantly positive association between of the HLA-DRB1*03, *04, *08, *10, *11, and *14 variants and elevated values of ESR in RA patients, but negative between HLA-DRB1*03, *13 and *15 alleles and elevated CRP values. Furthermore, our results confirm genetic susceptibility to RA in a female population to the members of the HLA-DRB1*04 and *03 allelic groups, the DRB1*04/DRB1*04 and DRB1*03/DRB1*04 genotypes, and the DRB1*04-DRB4* or DRB1*03-DRB3* haplotypes, which, therefore, represent risk factors for the development of this disease. According to our results, the DRB1*01/DRB1*15 and DRB1*07/DRB1*16 genotypes and the HLA-DRB5 gene locus represent a protective factor for RA. The presence of specific HLA-DRB1 gene variants increases the risk of developing RA, while other variants provide protection against disease. Therefore, HLA typing could be helpful in the prediction of RA development and establishing and confirming a definitive diagnosis of autoimmune diseases in some subjects. A strong association with the higher levels of ESR and CRP could be used to establish definitive diagnosis and introduce of early treatment of RA to prevent the occurrence of RA symptoms.

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Funding

No funding was received for this study.

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Affiliations

  1. Department of Laboratory Diagnostics, The Public Institution Health Centre of Sarajevo Canton, Sarajevo, Bosnia and Herzegovina

    Biljana Klimenta

  2. Department of Biology, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

    Hilada Nefic

  3. Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina

    Nenad Prodanovic

  4. Department of Medical Biochemistry, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

    Radivoj Jadric

  5. Department of Biochemistry, Clinical University Centre of Tuzla, Tuzla, Bosnia and Herzegovina

    Fatima Hukic

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  1. Biljana Klimenta
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  2. Hilada Nefic
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  3. Nenad Prodanovic
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  4. Radivoj Jadric
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  5. Fatima Hukic
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Contributions

All authors contributed to the design of the research and interpretation of the data, and critical revisions to the content. BK and HN contributed to data collection. HN analysed the data. The first draft of the manuscript was written by HN and all authors commented on the previous versions of the manuscript. All authors read and approved the final version of manuscript and take full responsibility for the accuracy or integrity of all parts of it. Writing review and editing: Springer Nature Research Editing Service.

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Correspondence to Hilada Nefic.

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Conflict of interest

Author Biljana Klimenta, author Hilada Nefic, author Nenad Prodanovic, author Radivoj Jadric, and author Fatima Hukic declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (the Research Ethics Committee of the Public Institution Health Centre of Sarajevo Canton, Bosnia and Herzegovina: 01-08-5080-2/16) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Klimenta, B., Nefic, H., Prodanovic, N. et al. Association of biomarkers of inflammation and HLA-DRB1 gene locus with risk of developing rheumatoid arthritis in females. Rheumatol Int 39, 2147–2157 (2019). https://doi.org/10.1007/s00296-019-04429-y

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  • DOI: https://doi.org/10.1007/s00296-019-04429-y

Keywords

  • Rheumatoid arthritis (RA)
  • C-reactive protein (CRP)
  • Erythrocyte sedimentation rate (ESR)
  • HLA-DRB1 gene