Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

Abstract

Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a onestandard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

“…These results could indicate that plasma apoE may have an immunosuppressive role in MS [9]. In agreement with this concept, our group observed that lower levels of plasma apoE might promote immune reactivity in these patients [12].…”

“…Moreover, LRP1 is also expressed in neurons and astrocytes and regulates BBB permeability [42]. This scenario is consistent with a reduction of inflammatory infiltrates and clinical disability by apoEderived peptides in EAE [43] and immunosuppressive and neuroprotective effects of plasma apoE in EAE [11] and MS patients [8][9][10]12].…”

Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis

“…Smoking has been reported to increase the risk for developing anti-interferon neutralizing antibodies [23, 24]. We had self-reported smoking status for 903 subjects.…”

Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

“…The mechanism of action of this treatment is known to increase this inflammatory marker of macrophage activation [11]. Notably, early in the course of NTZ therapy, plasma neopterin decreased to normal levels.…”

“…CD36 is an innate immune receptor expressed in endothelial cells and microglia/macrophages upregulated by PPAR γ [1]. Blood levels of metalloproteinase-9 (MMP-9), neopterin, and osteopontin (OPN) were also measured, since their expression may be modulated by PPAR [1] and MS therapies [8, 11, 12]. …”