Abstract
Multiple sclerosis (MS) is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT) reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils) or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical trials targeting BAFF with soluble receptor for MS treatment.
Highlights
Multiple sclerosis (MS) is a progressive autoimmune disease of the CNS
In the present prospective longitudinal study, we addressed the question of how blood BAFF levels are associated with the clinical course of relapsing-remitting MS (RRMS), including relapses, and short-term steroid (IVMP) treatment or disease-modifying treatments (DMT)
MS patients were divided into 3 subgroups on the basis of disease progression: 94 patients were recruited during a relapse, 50 patients were recruited during the stable phase and remained stable during the whole study period, and 26 patients were recruited during a remission phase and relapsed during the follow-up period
Summary
Multiple sclerosis (MS) is a progressive autoimmune disease of the CNS. The initial phase of MS is characterized by a relapsing-remitting course in 85% of patients [1]. Specific clinical features of MS include the development of unprovoked relapses, resulting in new damage to the CNS or worsening of existing neurological symptoms [2]. The most important clinical marker of MS activity is the number of relapses [4]. Immunological changes associated with MS disease progression have been extensively studied. T cells play a central role in disease pathogenesis [5]. Despite extensive research designed to identify specific MS biomarkers, no antibodies or immunological markers of MS have yet been validated for clinical use [7]
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