Increased serum levels of β2m‐free HLA class I heavy chain in multiple myeloma

Abstract

Summary. Serum levels of b2-microglobulin (b2m)-free HLA class I heavy chain (FHC) in 94 patients with multiple myeloma (MM) were higher than in 29 patients with monoclonal gammopathy of undetermined signi®cance (MGUS) (P 0´023) and in 97 sex-and age-matched healthy controls (P < 0´0001). Spearman correlation analysis indicated that in MM, FHC correlated with b2m (r 0´31, P 0´003) and the percentage of bone marrow plasma cells (BMPC%) (r 0´36, P 0´002), whereas b2m, in addition to BMPC% (r 0´43, P 0´0003), also correlated with creatinine levels (r 0´63, P < 0´0001), haemoglobin levels (r À0´35, P 0´0007) and patient age (r 0´34, P < 0´0011). Furthermore, MM patients with poor prognosis (b2m > 6 mg/l) displayed higher FHC levels than those with a better prognosis (b2m < 6mg/l) (P < 0´021). At variance from b2m, these levels were not in¯uenced by renal failure, as indicated by the lack of Spearman correlation of FHC with creatinine concentration and of statistical signi®cance between the median FHC concentration of MM patients with creatinine < 176´6 mmol/l and those with creatinine > 176´6 mmol/l (P 0´3). Strati®cation of patients according to disease activity and stage showed that FHC levels were only statistically different (P 0´04) for disease activity, whereas b2m and C-reactive protein were not. Taken together, our data indicate that serum FHC may be a useful disease marker in MM.

Total Soluble HLA Class I and Soluble HLA-G in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

“…The total soluble HLA class I complex, a couple of h 2 -microglobulin and the HLA class I heavy chain, seems more stable than the h 2 -microglobulinfree HLA class I heavy chain (31). FHC levels were significantly higher in multiple myeloma compared with MGUS and controls but did not vary across multiple myeloma stages (13). Similar minor correlations were observed between HLA-Is or FHC and h 2 -microglobulin (r = 0.29 or 0.31, respectively) and bone marrow plasmacytosis (r = 0.29 and 0.36, respectively).…”

“…These differences between cutaneous lymphoma and their nodal or leukemic counterparts could be partially explained by differences regarding the microenvironment and especially the cytokines involved (17). The serologic h 2 -microglobulin-free HLA class I heavy chain (FHC) has been recently studied (13). The total soluble HLA class I complex, a couple of h 2 -microglobulin and the HLA class I heavy chain, seems more stable than the h 2 -microglobulinfree HLA class I heavy chain (31).…”

“…The importance of finding a new marker independent of creatinine in multiple myeloma has been stressed because h 2 -microglobulin is influenced by renal insufficiency and is normal in about 10% of patients (6,32). No real prognostic factor analysis was done in the study reported by Perosa et al (13). In our study, the 2.1 Ag/L threshold, the upper limit of the inter-quartile range, was derived from overall survival prognostic analysis.…”

“…A recent study suggested that the soluble h 2 -microglobulinfree HLA class I heavy chain expression could be a disease marker in multiple myeloma (13). In a tumoral process, HLA-G expression could constitute a mechanism of tumor progression, and HLA-Gs expression has been shown in various cancer types and in some lymphoproliferative disorders (14 -17).…”

Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment

“…21 In line with these observations, both the cellular and soluble levels of the HLA-I molecules and the IL-6 receptor (IL-6R) chains, as well as the expression of costimulatory (CD40, CD80 and CD86) and adhesion (eg CD38) molecules and the CD95 death-related receptor have been associated with disease activity and/or an impaired immune response in MM. 4,17,[22][23][24][25][26][27][28] Despite this, to date no systematic studies have been performed in which the relationship between the expression of such molecules at cellular and soluble levels and the benign vs malignant behavior of MG has been analyzed.…”