Clinical relevance of soluble HLA-I and β2-microglobulin levels in non-Hodgkin's lymphoma and Hodgkin's disease

Plasma levels of beta-2 microglobulin (β2M), a subunit of the human leukocyte antigen-class I (HLA-I) molecule, correlate negatively with outcome in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). We examined the clinical relevance of soluble HLA-I (sHLA-I) levels in NHL and HD. Sera from consecutive NHL (n = 65) and HD (n = 37) patients were analyzed in a blinded manner. NHL and HD patients had significantly higher levels of sHLA-1 and β2M than control subjects. In NHL patients, sHLA-I levels correlated with clinical behavior in a fashion similar to that of β2M. However, multivariate analysis incorporating β2M, sHLA-I, and international prognostic index (IPI) indicated that NHL patients with elevated (>312.6 μg/100 mL) sHLA-I levels had significantly shorter survival, independent of IPI score as well as β2M. In HD patients, β2M but not sHLA-I levels were associated with clinical behavior. These findings not only establish the role of sHLA-I as an independent tumor marker in NHL that can be used to stratify patients, but also suggest that β2M and sHLA-I may reflect different biological processes in HD and NHL. Further studies are needed to assess whether the immunomodulatory properties of sHLA-I may be responsible for its divergence from β2M as an indicator of clinical behavior in HD.