Immunoglobulin-Like Transcript 2 (ILT2) Is Not Differentially Expressed in MGUS and Myeloma, but Appears To Be Downregulated at an Earlier Stage of Plasma Cell Disease.

Background: Immunoglobulin-like transcript 2 (ILT2/CD85j) belongs to the Ig superfamily and has homology to the killer cell inhibitory receptors (KIRs). It is expressed on natural killer (NK) cells, monocytes, macrophages, dendritic cells and (naive) B lymphocytes. A differential expression of ILT2 was described for monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Gene expression profiling studies found ILT2 to be downregulated 8.26 fold in myeloma as compared to MGUS, being the most differentially expressed gene between these two subsets. However, as RNA from CD138⁺ cells was used in this analysis, a varying percentage of normal, non-malignant plasma cells will impact on the results, especially in MGUS cases.

Aims: We aimed to delineate ILT2 expression in different plasma cell subsets (normal compared to monoclonal cells) in MGUS and MM and the eventual prognostic impact of a differential expression level.

Methods: ILT2 expression was measured by flow cytometry using a PE-conjugated antibody (clone HP-F1, Beckman Coulter) in a series of 30 MGUS patients and 91 myeloma patients. Phenotypically normal and malignant plasma cells were defined by differential expression of CD38, CD45, CD19 and CD56. Expression levels are given as mean fluorescence intensity (MFI) after correction for background staining.

Results: ILT2 was not differentially expressed in monoclonal plasma cells from patients with MGUS (MFI median 112.0, range 13.5–274.4) and myeloma (MFI median 96.6, range 0.4–454.5). In contrast, monoclonal cells from MGUS and MM showed a significantly lower expression of ILT2 as compared to phenotypically normal plasma cells in the majority of samples (p=0.007). Results were confirmed by quantitative real time PCR studies in 25 MM patients showing a linear correlation of ILT2 mRNA levels with the intensity of ILT2 protein expression. ILT2 levels did not vary with state of disease and showed no correlation with clinical parameters or prognosis in our series of myeloma patients.

Conclusions: In the majority of patients with monoclonal plasma cell disorders, ILT2 seems to be downregulated at an early stage of disease, i.e. upon transformation from a normal plasma cell to the MGUS/MM stage. The expression level of ILT2 in monoclonal plasma cells is neither correlated with the state of disease (MGUS versus newly diagnosed myeloma versus advanced disease) nor to prognosis of myeloma patients or other clinical parameters.