title: Clinical relevance of soluble HLA class I molecules in Waldenstrom Macroglobulinemia.
abstract: OBJECTIVE
  Waldenstrom Macroglobulinemia (WM) is a B-cell neoplasm characterised by secretion of IgM by lymphoplasmacytic bone marrow cells and by cytopenias and hypogammaglobulinemia in a subset of patients. Beta-2 microglobulin (b2m) is a major prognostic factor in WM and the heavy chain of HLA class I molecules, which are known to have immunosuppressive properties and have been implicated in the pathogeny of several malignancies.
  
  
  METHODS
  We assessed the serum levels of the total soluble HLA-I molecules and the HLA-Gs molecules in 105 patients with IgM-related disorders [WM (n = 42) and IgM MGUS (n = 63)], and compared the results to 41 healthy subjects.
  
  
  RESULTS
  We found higher levels of HLA-Is in WM, compared to IgM MGUS and healthy donors. HLA-Gs levels were similar in WM and in IgM MGUS, but higher than in healthy donors. The association between HLA-Is at the cut-off of 1.8 microg/mL and known markers of poor prognosis was then evaluated among WM patients using univariate and multivariate methods. Based on this, high HLA-Is level was strongly associated with high serum beta2M level >3 mg/L [OR = 2, (CI 95% 1.1-5.7); P = 0.04], age > 65 yrs [OR = 1.5, (CI 95% 0.5-4.1), P = 0.06] and haemoglobin < or =11.5 g/dL [OR = 3.3, (CI 95% 1.2-9.7); P = 0.03]. High levels of serum HLA-Is were also found in patients with cryoglobulinemia, however irrespectively of WM or IgM-MGUS status.
  
  
  CONCLUSIONS
  Together our results suggest a possible role for soluble MHC class I molecules in WM disease. Further investigations are necessary to further demonstrate the prognostic impact of soluble MHC class I molecules in Waldenstrom Macroglobulinemia.
authors.affiliation: Service des Maladies du Sang, CHRU, Lille, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Moreau
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Sebti
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.forename: Valérie
authors.initials: V
authors.lastname: Coiteux
authors.forename: Thomas
authors.initials: T
authors.lastname: Gastinne
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Le Friec
authors.forename: Nicholas
authors.initials: N
authors.lastname: Burwick
authors.forename: Laurence
authors.initials: L
authors.lastname: Amiot
authors.forename: Allen W
authors.initials: AW
authors.lastname: Ho
authors.forename: Stephanie
authors.initials: S
authors.lastname: Poulain
authors.forename: Bernadette
authors.initials: B
authors.lastname: Hennache
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Hunter
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Dessaint
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zorn
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
mesh_terms: D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I