Soluble HLA revisited

Abstract

The goal of this editorial is to revisit soluble human leukocyte antigens (sHLA) and to highlight the findings reported by Albitar et al. in this issue on the relation between sHLA levels in Non-Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD). We will review key aspects of sHLA including soluble HLA-G, which has received a lot of attention in recent publications. We will then address the role of sHLA in lymphoproliferative diseases and in solid organ tumors. Lastly, we will comment on the results of Albitar et al. and their relevance to clinical application in NHL.

Figure 1. Soluble HLA

HLA molecules are transmembrane glycoproteins that belong to the immunoglobulin superfamily. In human serum, several products have been detected: namely the intact molecule, likely a product of shedding; the products of alternative splicing which lack the transmembrane region; and proteolytic products lacking both the transmembrane and cytoplasmic regions.

Figure 2. Immunomodulatory role of sHLA in Non-Hodgkin’s Lymphoma

Non-Hodgkin’s Lymphoma (NHL) tumor cells produce elevated levels of sHLA-I molecules bearing tumor derived peptide antigens. The sHLA can then bind to the TCR of anti-tumor specific T cells and induce either apoptosis or anergy. sHLA can also bind to the CLIR or KIR of NK cells inducing NK cell apoptosis.