TY - JOUR
T1 - Biomarkers of systemic inflammation, soluble IL-2Rα and the multiple sclerosis-associated IL2RA SNP rs2104286 in healthy subjects and multiple sclerosis patients
AU - Buhelt, Sophie
AU - Søndergaard, Helle Bach
AU - Mahler, Mie Reith
AU - Cobanovic, Stefan
AU - Börnsen, Lars
AU - Ammitzbøll, Cecilie
AU - Oturai, Annette Bang
AU - Sellebjerg, Finn
N1 - Copyright © 2021. Published by Elsevier B.V.
PY - 2021/9
Y1 - 2021/9
N2 - Soluble interleukin-2 (IL-2) receptor α (sIL-2Rα) antagonizes IL-2 signaling and is involved in the pathogenesis of several immune-mediated diseases including multiple sclerosis (MS). The level of sIL-2Rα is affected by the MS-associated single nucleotide polymorphism (SNP) rs2104286. By use of ELISA and electrochemiluminescence, we investigated if 26 biomarkers of systemic inflammation were associated with sIL-2Rα and rs2104286 in cohorts of healthy subjects and MS patients in serum and heparin plasma. We found that sIL-2Rα significantly correlated with the level of tumor necrosis factor-α (TNFα) (r = 0.391, p = 0.002) in healthy subjects and the association was validated in a separate cohort. Additional, in healthy subjects we confirmed a previous report indicating that C-reactive protein (CRP) correlates with sIL-2Rα (r = 0.278, p = 0.034). None of the biomarkers of systemic inflammation were significantly associated with sIL-2Rα in MS patients. Furthermore, the MS-associated SNP rs2104286 was not significantly associated with any of the biomarkers of systemic inflammation in neither healthy subjects nor MS patients. We conclude that sIL-2Rα is associated with TNFα and CRP in healthy subjects. However, further research is required to confirm the use of sIL-2Rα as biomarker of systemic inflammation as well as to assess the mechanism underlying the observed correlation between levels of sIL-2Rα and TNFα.
AB - Soluble interleukin-2 (IL-2) receptor α (sIL-2Rα) antagonizes IL-2 signaling and is involved in the pathogenesis of several immune-mediated diseases including multiple sclerosis (MS). The level of sIL-2Rα is affected by the MS-associated single nucleotide polymorphism (SNP) rs2104286. By use of ELISA and electrochemiluminescence, we investigated if 26 biomarkers of systemic inflammation were associated with sIL-2Rα and rs2104286 in cohorts of healthy subjects and MS patients in serum and heparin plasma. We found that sIL-2Rα significantly correlated with the level of tumor necrosis factor-α (TNFα) (r = 0.391, p = 0.002) in healthy subjects and the association was validated in a separate cohort. Additional, in healthy subjects we confirmed a previous report indicating that C-reactive protein (CRP) correlates with sIL-2Rα (r = 0.278, p = 0.034). None of the biomarkers of systemic inflammation were significantly associated with sIL-2Rα in MS patients. Furthermore, the MS-associated SNP rs2104286 was not significantly associated with any of the biomarkers of systemic inflammation in neither healthy subjects nor MS patients. We conclude that sIL-2Rα is associated with TNFα and CRP in healthy subjects. However, further research is required to confirm the use of sIL-2Rα as biomarker of systemic inflammation as well as to assess the mechanism underlying the observed correlation between levels of sIL-2Rα and TNFα.
KW - Biomarkers
KW - Healthy Volunteers
KW - Humans
KW - Inflammation/genetics
KW - Interleukin-2 Receptor alpha Subunit/genetics
KW - Multiple Sclerosis/genetics
KW - Polymorphism, Single Nucleotide
UR - http://www.scopus.com/inward/record.url?scp=85111818085&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2021.103140
DO - 10.1016/j.msard.2021.103140
M3 - Journal article
C2 - 34304016
VL - 54
SP - 103140
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
M1 - 103140
ER -