I.V. SMAGINA^1, 2, A.S. PALASHENKO^1, 2, S.A. ELCHANINOVA¹, E.A. NAZARCHUK³, O.G. SIMONOVA³

 ¹Altai State Medical University, Barnaul

² Regional Clinical Hospital, Barnaul

³ Diagnostic Center of Altai Region, Barnaul

Contact details:

Smagina I.V. — MD, Professor of the Department of Psychiatry, Medical Psychology and Neurology, neurologist

Address: 40 prospekt Lenina, Barnaul, Russian Federation, 656038, tel.: +7-903-990-50-99, e-mail: siv7000@yаndеx.ru

Interactions of proinflammatory cytokine tumor necrosis factor alpha (TNF-a) with TNFR1 receptor are considered pathogenetically significant in multiple sclerosis (MS). However the clinical manifestations and relationship with the genetic features of changes in the production of these cytokines during exacerbation of the disease remain unclear.

The purpose — to evaluate the association of TNF-a, sTNFR1 levels in cerebrospinal fluid and blood serum with the course of MS and the polymorphisms of TNFRSF2 (rs1800629, rs361525), TNFR1 (rs4149584).

Material and methods. One hundred patients with remitting MS (24 women, 76 men), Caucasian, were examined during exacerbation and remission of the disease. The average value of patients disability was 3,4 ± 1,7 points by the Expanded Disability Status Scale (EDSS). Cytokine levels were measured by enzyme-linked immunosorbent assay, genotyping was performed by TaqMan probe technique.

Results. TNF-α and sTNFR1 levels in cerebrospinal fluid and blood serum were elevated in exacerbation of MS compared to remission. The increased risk of high rate of neurological deficit progression (increase by more than 0,75 EDSS points per year) was associated with concentrations above median TNF-α in blood serum in remission (OR = 11,00; CI 3,07–39,48; p < 0,001) and sTNFR1 in cerebrospinal fluid during exacerbation of MS (OR = 5,00; CI 1,24–105,00; p = 0,039). A three-year prospective follow-up revealed that the risk of MS exacerbations in the next three years is increased at a concentration of TNF-α above the median: in blood serum during remission (OR = 9,00; CI 1,14–71,02; p = 0,027) and in the cerebrospinal fluid in exacerbation of the disease (OR = 2,99, CI 1,84–6,09; p = 0,032).

Conclusion. The results indicate a possible relationship between the increased functional activity of TNF-α-TNFR1/sTNFR1 system and adverse course of remitting MS. Enhanced expression and/or shedding of TNFR1 in MS patients can be associated with the TNFRSF1A (rs4149584).

Key words: multiple sclerosis, tumor necrosis factor alpha, tumor necrosis factor alpha receptors, gene polymorphisms. 

(For citation: Smagina I.V., Palashenko A.S., Elchaninova S.A., Nazarchuk E.A., Simonova O.G. Relationship of TNF-alpha, sTNFR1 levels in cerebrospinal fluid and blood serum with TNFRSF2, TNFR1 polymorphisms and the course of multiple sclerosis. Practical Medicine. 2019. Vol. 17, № 7, P. 74-78)

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