Expression of cathepsins S and D signals a distinctive biochemical trait in CD34+ hematopoietic stem cells of relapsing–remitting multiple sclerosis patients

Background: The elucidation of mechanistic aspects of relapsing–remitting multiple sclerosis (RRMS) pathogenesis may offer valuable insights into diagnostic decisions and medical treatment. Results: Two lysosomal proteases, cathepsins S and D (CatS and CatD), display an exclusive pattern of expression in CD34+ hematopoietic stem cells (HSCs) from peripheral blood of acute MS (A-MS) patients ( n = 20). While both enzymes normally exist as precursor forms in the HSCs of healthy individuals ( n = 30), the same cells from A-MS patients consistently exhibit mature enzymes. Further, mature cathepsins are expressed at lower rates in stable MS subjects (S-MS, n = 15) and revert to precursor proteins after interferon-β1a treatment ( n = 5). Mature CatD and CatS were induced in HSCs of healthy donors that were either co-cultured with PBMCs of A-MS patients or exposed to their plasma, suggesting a functional involvement of soluble agents. Following HSC exposure to several cytokines known to be implicated in MS, and based on relative cytokine levels displayed in A-MS, S-MS and control individuals, we identified IL-16 as a specific cell signaling factor associated with cathepsin processing. Conclusions: These data point to an evident correlation between CatS and CatD expression and MS clinical stage, and define a biochemical trait in HSCs with functional, medical, and diagnostic relevance.

Concerning the Genetics of Mental Features

It is immediately apparent, that the difficulties encountered in studies of the genetics of the mind are formidable, for several reasons. In the first place, the traits concerned are difficult or impossible to classify or to measure with accuracy. In the second place, they may be unstable towards environmental influence; and they vary with age, or exhibit periodic changes.It is therefore not surprising that our understanding of genetic mechanisms is limited in those conditions where analysis has been carried out merely on the basis of the mental traits.The situation is strikingly different in the conditions where an association has been found between a mental trait and some clearly recognisable physical or biochemical trait. As we all know, in several such cases an exact genetic analysis in Mendelian terms has been found possible, for instance in the amaurotic idiocies and phenylketonuria.