title: Soluble and membrane levels of molecules involved in the interaction between clonal plasma cells and the immunological microenvironment in multiple myeloma and their association with the characteristics of the disease.
abstract: Clonal plasma cells (PC) from different types of monoclonal gammopathies (MG) display distinct phenotypes consistent with an increased antigen-presentation and T-cell costimulation in MG of undetermined significance that deteriorates in malignant conditions. Expression of other cell surface and soluble molecules (e.g. adhesion/proliferation molecules) involved in the interaction between clonal PC and the bone marrow (BM) microenvironment has also been related to malignant PC, although the exact clinical significance of their expression remains largely unknown. Analysis of cell surface levels of several of these molecules in multiple myeloma (MM) patients shows an association between lower expression on BMPC of the HLA-I and beta2-microglobulin antigen-presenting molecules, the CD126 and CD130 IL6 receptor (IL6R) chains, and CD38, and adverse prognostic features of the disease. Likewise, patients showing higher soluble levels of antigen-presenting molecules (HLA-I and beta2-microglobulin), IL6R and CD95 tended to be associated with more aggressive disease behavior. In contrast, CD40, CD86, CD56, CD19, and CD45 were not associated with patients' outcome. Interestingly, upon considering the ratio between the soluble and PC membrane expression of each molecule, an increased adverse prognostic impact was observed for both HLA-I and beta2-microglobulin, but not for the other molecules. Multivariate analysis confirmed the independent prognostic value of cell surface expression of CD126 on BMPC together with serum beta2-microglobulin and LDH. In summary, our results show an abnormal distribution of the cellular and soluble compartments of the HLA-I, IL6R, and to a lower extent, CD95 molecules, in MM, associated with the clinical characteristics and behavior of the disease.
authors.affiliation: Cytometry Service, Department of Medicine, Universidad de Salamanca, and Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Perez-Andres
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Marta
authors.initials: M
authors.lastname: Martin-Ayuso
authors.forename: Natalia
authors.initials: N
authors.lastname: De Las Heras
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Moro
authors.forename: Guillermo
authors.initials: G
authors.lastname: Martin-Nuñez
authors.forename: Josefina
authors.initials: J
authors.lastname: Galende
authors.forename: Rebeca
authors.initials: R
authors.lastname: Cuello
authors.forename: Isabel
authors.initials: I
authors.lastname: Abuín
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Moreno
authors.forename: Mercedes
authors.initials: M
authors.lastname: Domínguez
authors.forename: Jose
authors.initials: J
authors.lastname: Hernandez
authors.forename: Gema
authors.initials: G
authors.lastname: Mateo
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000368:Aged; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D010950:Plasma Cells / Q000378:metabolism*; D011379:Prognosis; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D016896:Treatment Outcome; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D006680:HLA Antigens; D019947:Receptors, Interleukin-6; D019014:fas Receptor