title: Expression of cathepsins S and D signals a distinctive biochemical trait in CD34+ hematopoietic stem cells of relapsing-remitting multiple sclerosis patients.
abstract: 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.
authors: Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Perugia, Italy.
authors: Sabata
authors: S
authors: Martino
authors: Simona
authors: S
authors: Montesano
authors: Ilaria
authors: I
authors: di Girolamo
authors: Roberto
authors: R
authors: Tiribuzi
authors: Maria
authors: M
authors: Di Gregorio
authors: Antonio
authors: A
authors: Orlacchio
authors: Alessandro
authors: A
authors: Datti
authors: Paolo
authors: P
authors: Calabresi
authors: Paola
authors: P
authors: Sarchielli
authors: Aldo
authors: A
authors: Orlacchio
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D002402:Cathepsin D / Q000096:biosynthesis*; D002403:Cathepsins / Q000096:biosynthesis*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood*
chemical_list: D018952:Antigens, CD34; D002403:Cathepsins; C028217:cathepsin S; D002402:Cathepsin D
keywords: cathepsins; diagnosis; multiple sclerosis; stem cell