Relationship Between T-helper 1 Inflammatory Biomarkers and Hematological Index Responses in Patients With Multiple Sclerosis

Abstract

Background Multiple sclerosis is a chronic, progressive, disabling disease associated with a high rate of infection, evidence of chronic inflammation, and a high mortality rate. Abnormalities of serum cytokines and changes in the activity of inflammatory cells were associated with relapsing-remitting multiple sclerosis (MS-RR). This study aims to introduce new inflammatory ratios derived from hematological and lipid indices as discriminators of T-helper (Th)-1/Th-2 activity in RR-MS. Methods This cross-sectional study recruited 40 RR-MS patients and 30 healthy individuals. Th-1 and Th-2 cytokines, including interferon-y (INF-γ), tumor necrosis factor-a (TNF-α), interleukin (IL)-4, IL5, and IL-10 measurements, were performed using enzyme-linked immunosorbent assay technique. Hematological indices and lipid profiles were measured as routine laboratory investigations. SPSS Statistics version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) was used for data analysis. An independent sample t-test was used to compare two means, and Spearman correlation was used to assess the correlation between different markers. A p-value of <0.05 was considered statistically significant. Results Serum levels of Th-1 and Th-2 cytokines in RR-MS were significantly higher than in healthy subjects (p<0.001). The ratios of INF-γ-to-IL4 and TNF-α-to-IL-10 were significantly lower than the corresponding ratios of healthy subjects (p<0.001). Monocyte-to-high-density lipoprotein ratio (MHDLR) is significantly lower (p<0.001) than healthy subjects (9.4±1.62 vs. 6.4±1.1, respectively) and significantly correlated positively with INF-γ (r=0.417) and TNF-α (r=0.565), while MHDLR inversely correlated with IL-4 (r=-0.445) and IL-5 (r =-0.386). Lymphocyte-to-non-high-density lipoprotein ratio (LNHDLR) is significantly (p<0.001) higher than healthy subjects (18.2±3.3 vs. 13.1±2.2, respectively) and significantly correlated inversely with INF-γ (r=-0.484) and TNF-α (r=-0.456), while LNHDLR positively correlated with IL-4 (r=0.565) and IL-5 (r=0.532). The area under the curve (AUC) of MHDLR mimics the AUCs of Th-1 cytokines, while the AUC of LNHDLR mimics the AUCs of Th-2 cytokines. Conclusions MHDLR and LNHDLR served as pro-inflammatory and anti-inflammatory markers, respectively, with profiles similar to TH-1 and Th-2 cytokines. These findings suggest that these lipid-related ratios are non-invasive, cost-effective biomarkers for monitoring RR-MS patients' immune response and inflammatory status.

Keywords: biomarkers; cytokines; hematological indices; lipoproteins; multiple sclerosis.

Figure 1. AUC of the Th-1 and Th-2 cytokines, inflammatory indices, and ratios derived from hematological and lipid indices taking the cutoff level of hs-CRP > 3 mg/L as a discriminator

ROC: receiver-operating characteristic, NLR: neutrophil-to-lymphocyte ratio, LMR: lymphocyte-to-monocyte ratio, PLR: platelet-to-lymphocyte ratio, MHDLR: monocyte-to-high-density lipoprotein ratio, LNHDLR: lymphocyte-to-non-high-density lipoprotein ratio, INF-γ: interferon-y, TNF-α: tumor necrosis factor-a, IL: interleukin, hs-CRP: high-sensitivity C-reactive protein, AUC: area under the curve