An IL-5 Single-Nucleotide Polymorphism Influences Neuroinflammation and Prospective Disease Activity in Multiple Sclerosis.
Ettore DolcettiFabio ButtariAntonio BrunoFederica AzzoliniLuana GilioAngela BorrelliVeronica Di CaprioGianluca LauritanoGiovanni GalifiStefano GambardellaRosangela FereseEmiliano GiardinaValentina RovellaRoberto FurlanAnnamaria FinardiAlessandra MusellaSara BallettaGeorgia MandolesiDiego CentonzeMario Stampanoni BassiPublished in: International journal of molecular sciences (2024)
(1) Multiple sclerosis (MS) is identified by a complex interaction between central inflammation and neurodegeneration. Genetic individual variability could play a significative role in clinical presentation. The interleukin-5 (IL-5) rs2069812 single-nucleotide polymorphism (SNP) seems to define the clinical course of Th2 autoimmune diseases, while its role in MS has never been investigated. (2) In a group of 230 patients diagnosed with relapsing-remitting MS (RR-MS) or progressive MS (P-MS) and controls (IC), rs2069812 polymorphism, cerebrospinal fluid (CSF) levels of inflammatory mediators, and clinical and demographic characteristics were determined. In RR-MS patients, No Evidence of Disease Activity (NEDA-3) at three years of follow-up was detected. (3) We identified higher levels of proinflammatory cytokines, particularly IL-2 (median [IQR], RR-MS = 0.2 [0-0.7]; P-MS = 0.1 [0-1.6]; IC = 0.1 [0.0-0.1]; p < 0.005), IL-6 (RR-MS = 0.9 [0.3-2.3]; P-MS = 0.8 [0.1-2.7]; IC = 0.1 [0.0-0.5]; p < 0.005), IL-12 (RR-MS = 0.5 [0-1.1]; P-MS = 0.5 [0-1.1]; IC = 0.0 [0.0-0.3]; p < 0.005), and GM-CSF (RR-MS = 15.6 [4.8-26.4]; P-MS = 14 [3.3-29.7]; IC = 8.9 [4.7-11.7]; p < 0.005) in MS patients compared with IC. Conversely, anti-inflammatory cytokines, specifically IL-5 (RR-MS = 0.65 [0-2.4]; P-MS = 0.1 [0-0.8]; IC = 1.7 [0.6-2.8]; p < 0.005) and IL-1ra (RR-MS = 14.7 [4.9-26.4]; P-MS = 13.1 [4.7-22.2]; IC = 27.8 [17.7-37.6]; p < 0.005) were higher in controls. According to rs2069812, in MS patients, the T-allele was associated with higher concentrations of proinflammatory mediators (IL-2, CT/TT = 0.2 [0.0-2.0]; CC = 0.1 [0.0-0.4], p = 0.015; IL-6, CT/TT = 1.2 [0.4-3.2] vs. CC = 0.7 [0.1-1.7], p = 0.007; IL-15, CT/TT = 0.1 [0.0-9.5] vs. CC = 0.0 [0.0-0.1], p = 0.019; and GM-CSF, CT/TT = 0.1 [0.0-0.6] vs. CC = 0.05 [0.0-0.1], p < 0.001), and CC was associated with anti-inflammatory mediators (IL-5, CT/TT = 0.03 [0.0-1.9] vs. CC = 1.28 [0.0-2.7], p = 0.001; IL-1ra, CT/TT = 12.1 [4.1-25.9] vs. CC = 18.1 [12.1-26.9], p = 0.006). We found the same differences in RR-MS patients (IL-2, T-allele median [IQR] = 0.3 [0.0-2.0] vs. C-allele, median [IQR] = 0.04 [0.0-0.3]; p = 0.005; IL-6, T-allele, median [IQR] = 1.3 [0.4-3.3] vs. C-allele, median [IQR] = 0.6 [0.03-1.5]; p = 0.001; IL-15, T-allele, median [IQR] = 0.1 [0.0-9.5] vs. C-allele, median [IQR] = 0.0 [0.0-0.1]; p = 0.008; GM-CSF, T-allele, median [IQR] = 0.1 [0.0-97.9] vs. C-allele, median [IQR] = 0.0 [0.0-0.001]; p < 0.001; IL-5, T-allele, median [IQR] = 0.02 [0.0-2.2] vs. C-allele, median [IQR] = 1.5 [0.0-2.9]; p = 0.016; and IL-1ra, T-allele, median [IQR] = 12.1 [4.3-26.4] vs. C-allele, median [IQR] = 18.5 [12.7-28.3]; p = 0.006) but not in P-MS, except for IL-5 (T-allele, median [IQR] = 0.1 [0-0.23] vs. C-allele, median [IQR] = 0.6 [0.0-2.5]; p = 0.022). Finally, we identified an association between CC in RR-MS patients and NEDA-3 after three years of follow-up ( p = 0.007). (4) We describe, for the first time, the role of an SNP of the IL-5 gene in regulating central neuroinflammation and influencing clinical course in MS patients.
Keyphrases
- multiple sclerosis
- mass spectrometry
- ms ms
- end stage renal disease
- ejection fraction
- newly diagnosed
- disease activity
- chronic kidney disease
- white matter
- peritoneal dialysis
- rheumatoid arthritis
- computed tomography
- traumatic brain injury
- prognostic factors
- magnetic resonance imaging
- dna methylation
- copy number
- ankylosing spondylitis
- contrast enhanced
- idiopathic pulmonary fibrosis
- blood brain barrier
- pet ct
- high density
- cognitive impairment
- lps induced
- interstitial lung disease