Sequencing the immunopathologic heterogeneity in multiple sclerosis

Plenas et al. are to be congratulated on the application of cutting edge cell and molecular biologic techniques to address central issues regarding the immune-pathogenesis multiple sclerosis (MS) of lesions.1 This was a demanding study with regard to acquisition of patient material, experimental design, quality and quantity of labor involved, and cost. As emphasized in this report, a challenge in MS is to define the immunologic events ongoing in actual lesions and then determine whether and how these may be reflected or monitored by analysis of more readily available tissue samples such as cerebrospinal fluid (CSF) or blood. The authors specifically address the concept of there being distinct phenotypes of early lesions among MS patients, categorized as patterns 1–4.2 Pattern 2 lesions have been described to feature immunoglobulin (Ig) and complement deposition in addition to inflammatory cell infiltration and myelin destruction and were the most frequent lesion pattern observed in the initial combined biopsy and autopsy sample. Data supporting the distinct features of pattern 2 lesions include therapeutic responses to plasma exchange therapy3 and potentially presence of unique serum autoantibody signatures.4 The authors acknowledge the controversy that exists regarding this concept, providing rationale for generating more direct evidence as in this study.