Abstract

30% of Alemtuzumab treated Multiple Sclerosis (MS) patients develop autoimmune disease (AID). Genetically determined pre-treatment serum IL-21 levels are a putative biomarker for this phenomenon and may be of clinical value, informing treatment choice and providing insights into patterns of disease expression and co-morbidity in MS. We evaluated IL-21 levels in sera of 42 normal controls and 248 MS patients; including 63 patients with highly active MS (HAMS), 43 of whom had been treated with Alemtuzumab, 86 age/sex matched disease controls, 36 patients seen serially during and after relapse and 59 with progressive disease. IL-21 concentrations were correlated with disease type, pre-treatment mean annualised relapse rate (MARR) and AID. Serum IL-21 levels in longitudinal samples were stable, varying by >10% in both relapsing and non-relapsing patient groups. There was an exponential association between IL-21 and MARR (r²=0.56, p=0.03). Levels were higher in patients with HAMS than other patient groups or controls (686 pg/ml vs 286 pg/ml and 241 pg/ml, p<0.001). High IL-21 levels (>350 pg/ml) were specific (93%) but non-sensitive (24%) for HAMS. 14/62 Alemtuzumab treated patients developed AID and high pre-treatment serum levels predicted this with high sensitivity (86%) and specificity (90%). This study confirms a role for serum IL21 levels as a pre-treatment biomarker for post-Alemtuzumab AID and suggests an association between IL-21 expression and MS relapse activity.