title: The plasma levels of soluble HLA-G molecules correlate directly with CD34+ cell concentration and HLA-G 14bp insertion/insertion polymorphism in cord blood donors.
abstract: BACKGROUND
  Cord blood provides haematopoietic stem cells for allogeneic transplantation and, thanks to the naivety of its immune system, has several advantages over other sources of stem cells. In the transplantation setting, the presence of immunosuppressive human leucocyte antigen (HLA)-G molecules has been advocated to prevent both rejection and Graft-versus-Host disease. HLA-G is physiologically expressed throughout pregnancy and is contained in cord blood at birth. Moreover, it has recently been reported that not only cord blood mesenchymal cells, but also CD34+ cell progenies produce soluble HLA-G (sHLA-G). We tried to identify the largest producer of sHLA-G among 85 healthy cord blood donors at Pavia Cord Blood Bank, correlating the sHLA-G concentration with the HLA-G 14bp insertion/deletion (INS/DEL) genotype and CD34+ cell concentration.
  
  
  METHODS
  We measured sHLA-G levels in 36 cord blood plasma stored at -20 °C for 2 months and 49 cord blood plasma stored at -196 °C for 4-6 years, by enzyme-linked immunosorbent assay. All cord blood donors were genotyped for the HLA-G 14bp INS/DEL polymorphism by polymerase chain reaction. For each cord blood unit, we measured the cell concentration by flow cytometry.
  
  
  RESULTS
  We did not find differences in sHLA-G levels between cord blood plasma aliquots stored for 4-6 years at -196 °C and cord blood plasma aliquots stored for 2 months at -20 °C. We observed a higher sHLA-G concentration in cord blood plasma donors who carried the HLA-G 14bp INS/INS genotype and had higher CD34+ cell concentrations (P=0.006).
  
  
  CONCLUSIONS
  This is the first report showing that the best cord blood stem cell donor is also the best sHLA-G producer, particularly if genetically characterized by the HLA-G 14bp INS/INS genotype. If the therapeutic role of sHLA-G molecules were to be finally established in the transplantation setting, our data suggest that cord blood plasma donors can provide a safe source of allogeneic sHLA-G immunosuppressive molecules ready for transfusion.
authors: Immunogenetics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Cristina
authors: C
authors: Capittini
authors: Pavia Cord Blood Bank, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Paola
authors: P
authors: Bergamaschi
authors: Serological and Molecular Diagnostics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Sara
authors: S
authors: Sachetto
authors: Serological and Molecular Diagnostics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Mariarosa
authors: M
authors: Truglio
authors: Serological and Molecular Diagnostics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Monica
authors: M
authors: Viola
authors: Pavia Cord Blood Bank, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Andrea
authors: A
authors: Marchesi
authors: Pavia Cord Blood Bank, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Valeria
authors: V
authors: Genovese
authors: Pavia Cord Blood Bank, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Bina
authors: B
authors: Romano
authors: Immunogenetics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Marco
authors: M
authors: Guarene
authors: Serological and Molecular Diagnostics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Rossella
authors: R
authors: Poma
authors: Immunogenetics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Miryam
authors: M
authors: Martinetti
authors: Clinical Epidemiology and Biometric Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Carmine
authors: C
authors: Tinelli
authors: Pavia Cord Blood Bank, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Laura
authors: L
authors: Salvaneschi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D018952:Antigens, CD34 / Q000032:analysis; D001772:Blood Cell Count; D001782:Blood Donors; D005091:Exons / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D059951:HLA-G Antigens / Q000097:blood* / Q000235:genetics; D006412:Hematopoietic Stem Cells; D006801:Humans; D054643:INDEL Mutation; D007231:Infant, Newborn; D008297:Male; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D012995:Solubility
chemical_list: D020413:3' Untranslated Regions; D018952:Antigens, CD34; D059951:HLA-G Antigens
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