KIRs and their HLA ligands in remitting-relapsing multiple sclerosis

Killer Immunoglobulin-like Receptor (KIR) genes may affect both resistance and susceptibility to autoimmune disorders, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. To evaluate the involvement of KIRs and their HLA ligands in the development of MS we performed genotyping of HLA -A, -B, -Cw, -DRB1 and KIRs loci in 121 RRMS patients and 103 healthy controls (HC). Results evidenced a possible protective role of the activating KIR2DS1 gene (p(y) = 0.001; OR:0.38), enhanced in the presence of its ligand group HLA-C2 (p(y) = 0.0001; OR:0.23). Our data suggest that the presence of functional compounds of activating KIR receptors together with their HLA ligands, allowing the immunomodulatory function of NK cells, may have a protective role against the disease

Detection of disability worsening in relapsing-remitting multiple sclerosis patients: a real-world roving Expanded Disability Status Scale reference analysis from the Italian Multiple Sclerosis Register

Background and purpose: In relapsing-remitting multiple sclerosis patients (RRMS) disability progressively accumulates over time. To compare the cumulative probability of 6-month confirmed disability-worsening events using a fixed baseline or a roving Expanded Disability Status Scale (EDSS) reference, in a real-world setting. Methods: A cohort of 7964 RRMS patients followed for 2 or more years, with EDSS scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register. The overall probability of confirmed disability-worsening events and of confirmed disability-worsening events unrelated to relapse was evaluated using as reference a fixed baseline EDSS score or a roving EDSS score in which the increase had to be separated from the last EDSS assessment by at least 6 or 12 months. Results: Using a fixed baseline EDSS reference, the cumulative probability of 6-year overall confirmed disability-worsening events was 33.2%, and that of events unrelated to relapse was 10.9% (33% of overall confirmed disability-worsening events). Using a roving EDSS, the proportions were respectively 35.2% and 21.3% (61% of overall confirmed disability-worsening events). Conclusions: In a real-world setting, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability-worsening events unrelated to relapse in RRMS patients