Unveiling a novel immunomodulatory role for Interferon-β therapy in Multiple Sclerosis: the selective reduction of pathogenic memory B cells — ASN Events

Unveiling a novel immunomodulatory role for Interferon-β therapy in Multiple Sclerosis: the selective reduction of pathogenic memory B cells (#160)

Fabiana Rizzo 1 , Elena Giacomini 1 , Martina Severa 1 , Rosella Mechelli 2 , Silvia Romano 2 , Vito Antonio Gerardo Ricigliano 2 , Marco Salvetti 2 , Eliana Marina Coccia 1
  1. Istituto Superiore di Sanità, Rome, ITALY, Italy
  2. S. Andrea Hospital-La Sapienza University , Rome, Italy

Objective: B cells are emerging as central players in Multiple sclerosis (MS) pathogenesis, thus we sought to evaluate whether IFN-β therapy may regulate B cell responses in Relapsing Remitting MS (RRMS) patients.

Methods: Apoptotic phenotype of naïve and memory B cells was analyzed longitudinally in MS patients before and after therapy either by staining with Annexin-V and 7-actinomycin D or by evaluating intracellular Caspase 3 activation and Fas Receptor (Fas) expression. In vitro experiments were also conducted treating with an anti-Fas mAb PBMCs isolated from MS patients.

Results. Our results showed that IFN-β specifically targets the B cell compartment by reducing memory B cell frequency. Enhanced expression of Fas, Annexin-V and active Caspase 3 was found in memory B cells upon IFN-β therapy, suggesting a specific induction of apoptosis in this population also confirmed by in vitro experiments with anti-Fas mAb. Taking into account that memory B cells represent the major Epstein barr-virus (EBV) reservoir and that EBV represents one of the candidate for MS etiopathogenesis, the ability of IFN-β therapy to reduce the enhanced expression of the EBV latent LMP2A transcript found in MS patients as compared to healthy subjects, indicates that this treatment may also exert some antiviral effects in MS patients.

Conclusions. All our findings suggest that the specific reduction of memory B cells is a novel effect induced by IFN-β therapy, similarly to what found for the anti-CD20 mAb Rituximab. Thus, IFN-β therapy may play a dual role by exerting both immunomodulatory and anti-viral activities, modulating pathogenic B cell responses and controlling EBV infection in MS patients via the depletion of EBV-harboring cells.

This work was supported by FISM grant (#2009/R/7 to EMC).