Matrix metalloproteinase 9 is decreased in natalizumab‐treated multiple sclerosis patients at risk for progressive multifocal leukoencephalopathy

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Natalizumab (NTZ), an inhibitor of the α4 integrin that prevents inflammatory T cells from entering the brain, is an effective monoclonal antibody therapy for relapsing–remitting multiple sclerosis (RRMS).1 Despite its proved efficacy, the occurrence of an opportunistic central nervous system infection, progressive multifocal leukoencephalopathy (PML), in patients treated with NTZ led to therapy restriction due to risk–benefit considerations.
Currently, the risk of PML can be quantified according to an algorithm that incorporates the following 3 risk factors: (1) duration of NTZ treatment, (2) presence of anti–John Cunningham virus (JCV) antibodies, and (3) previous treatment with immunosuppressants.2 However, it has been demonstrated that this risk stratification algorithm is not effective enough in preventing the development of new PML cases.4 In this context, additional biomarkers are needed in clinical practice to identify patients at greater risk for PML. Recently, a decreased expression of L‐selectin (CD62L) by peripheral blood CD4+ T cells was observed in NTZ‐treated patients at high risk for PML and proposed as a biomarker to measure the individual PML risk in multiple sclerosis (MS) patients under NTZ treatment5; however, debate on the clinical utility of this biomarker is still open.7 The potential role of other prognostic body fluid biomarkers has yet to be determined.
In the present study, we pursued the identification of molecular biomarkers associated with PML development using different techniques in peripheral blood samples obtained before the initiation of therapy and at different time points after treatment from RRMS patients classified according the development (or not) of NTZ‐associated PML. Our findings indicate that proangiogenic factors, particularly matrix metalloproteinase 9 (MMP9), may help to discriminate between patients with different PML outcomes.

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