Clinical relevance of soluble HLA class I molecules in Waldenstrom Macroglobulinemia.
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.
Moreau
Anne-Sophie
AS
Service des Maladies du Sang, CHRU, Lille, France.
Sebti
Yasmine
Y
Duhamel
Alain
A
Roccaro
Aldo M
AM
Coiteux
Valérie
V
Gastinne
Thomas
T
Le Friec
Gaëlle
G
Burwick
Nicholas
N
Amiot
Laurence
L
Ho
Allen W
AW
Poulain
Stephanie
S
Hennache
Bernadette
B
Hunter
Zachary R
ZR
Dessaint
Jean-Paul
JP
Ghobrial
Irene M
IM
Treon
Steven P
SP
Facon
Thierry
T
Zorn
Emmanuel
E
Leleu
Xavier
X
D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology*
D015395:Histocompatibility Antigens Class I