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Tumor necrosis factor alpha (TNF-α) and its soluble receptors are associated with disability, disability progression and clinical forms of multiple sclerosis

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Abstract

Background

The association between tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1 and sTNFR2 with clinical characteristics of multiple sclerosis (MS) remains unclear.

Objective

To examine whether TNF-α, sTNFR1 and sTNFR2 are associated with MS diagnosis, disability, disability progression and clinical forms of MS.

Materials and subjects

The study included 147 patients with relapsing–remitting MS (RRMS), 21 with progressive clinical forms (ProgMS) and 70 controls. Expanded Disability Status Scale (EDSS) evaluated disability as mild (EDSS < 3.0) or moderate/high (EDSS ≥ 3.0). Multiple Sclerosis Severity Score (MSSS) evaluated disability progression as no progression (MSSS < 5) and progression (MSSS ≥ 5). Baseline data of subjects and plasma levels of TNF-α, sTNFR1, sTNFR2 were obtained.

Results

The MS diagnosis explained 44.6% and 12.3% of TNF-α and sTNFR2 levels, respectively. Moderate/high disability and disability progression were best predicted by sTNFR1 and age (positively) and ProgMS were best predicted by sTNFR1 (positively) and sTNFR2 (negatively), coupled with age and sex. A composite score reflecting the sTNFR1/sTNFR2 ratio showed a positive association with ProgMS after adjusting for age and sex.

Conclusion

Increased sTNFR1 and age were positively associated with disability and disability progression, whereas increased sTNFR1 (positively) and sTNFR2 (negatively) were associated with ProgMS, suggesting a distinct role of them in the immunopathological mechanisms of MS.

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Acknowledgements

The study was supported by grants from the Coordination for the Improvement of Higher Level of Education Personnel (CAPES) of Brazilian Ministry of Education; Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq); and State University of Londrina (PROPPG). We thank the University Hospital of State University of Londrina for technical supports.

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Authors and Affiliations

  1. Laboratory of Applied Immunology, Health Sciences Center, University of Londrina, Paraná, Brazil

    Claudia Mara Ribeiro, Sayonara Rangel Oliveira, Daniela Frizon Alfieri, Tamires Flauzino, Andréa Name Colado Simão & Edna Maria Vissoci Reiche

  2. Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil

    Sayonara Rangel Oliveira, Andréa Name Colado Simão & Edna Maria Vissoci Reiche

  3. Hospital Santa Casa de Misericórdia de Londrina, Londrina, Brazil

    Damacio Ramón Kaimen-Maciel

  4. IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia

    Michael Maes

  5. Department of Psychiatry, King Chulalongkorn Memorial Hospital, Chulalongkorn, Bangkok, Thailand

    Michael Maes

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  1. Claudia Mara Ribeiro
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Correspondence to Edna Maria Vissoci Reiche.

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Ribeiro, C.M., Oliveira, S.R., Alfieri, D.F. et al. Tumor necrosis factor alpha (TNF-α) and its soluble receptors are associated with disability, disability progression and clinical forms of multiple sclerosis. Inflamm. Res. 68, 1049–1059 (2019). https://doi.org/10.1007/s00011-019-01286-0

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  • DOI: https://doi.org/10.1007/s00011-019-01286-0

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