Serum β2-Microglobulin for Staging and Monitoring of Multiple Myelomas and Other Non-Hodgkin Lymphomas

Abstract

Background: In lymphoproliferative disorders serum β₂-microglobulin (β₂m) can be useful as a clinical marker. Material and Methods: β₂m measurements were carried out with a new assay of Hoffmann-La Roche, which is a one-step solid-phase enzyme immunoassay with competitive inhibition. Sera of 81 healthy subjects, 42 patients with renal failure, 108 patients with monoclonal gammopathies [3 monoclonal gammopathies of undetermined significance (MGUS), 91 multiple myeloma (MM), 14 macroglobulinemia (MG)], and 11 patients with non-Hodgkin lymphoma (NHL) were tested. In addition β₂m was determined during follow-up of 29 patients with myeloma and lymphoma. Results: β₂m values of normal sera ranged from 1.0 to 3.0 mg/l in 97.5%. Patients with renal malfunction had the highest β₂m concentrations (60 mg/l) with significant correlation (ρ < 0.01) to serum creatinine (r=0.45). 57% of the patients with MM and NHL had raised β₂m levels when compared to healthy controls. Serum β₂m values did not correlate with the serum levels of monoclonal immunoglobulins. Using the myeloma staging system of Durie and Salmon, a strong association of pretreatment serum β₂m with advanced stage of disease was found. In stages II and III, β₂m levels were significantly higher than in stage I (p < 0.001). Seven patients with smoldering myeloma showed β₂m concentrations within the normal range. No association with histologic cell types of myeloma was found. In the follow-up of patients with myeloma, β₂m values decreased with response to chemotherapy and were low in stable remission. At relapse very high β₂m concentrations were associated with a poor prognosis. Conclusion: Serum β₂m appears to be a good prognostic marker in MM independent of the paraprotein concentration. In MM and also in other NHL, β₂m determination helps to optimize therapy.

Structural Features of Amyloid Fibrils Formed from the Full-Length and Truncated Forms of Beta-2-Microglobulin Probed by Fluorescent Dye Thioflavin T

“…β2M facilitates the successful folding and the cell surface exposure of the major histocompatibility complex class I molecules [ 1 , 2 ]. Normally, β2M concentration in blood plasma is approximately 1–3 μg/mL, while about 2–4 mg/kg of the protein is synthesized daily in the body, and its half-life is about 2.5 h [ 3 , 4 , 5 ]. Approximately 95% of the β2M elimination occurs through glomerular filtration (with subsequent reabsorption and intracellular proteolysis in the proximal tubules), thus its concentration in blood plasma is directly related to the kidneys functioning.…”

“…Approximately 95% of the β2M elimination occurs through glomerular filtration (with subsequent reabsorption and intracellular proteolysis in the proximal tubules), thus its concentration in blood plasma is directly related to the kidneys functioning. The β2M levels in chronic renal failure may increase by 60 times due to a significant (10–15 times) increase in the protein excretion time [ 5 , 6 ]. Large amounts of β2M can been found in the urine of patients with impaired nephrotic reabsorption of proteins from the primary filtrate [ 7 ].…”

Poley S, et al: Serum β2-microglobulin for staging and monitoring of multiple myelomas and other non-Hodgkin lymphomas. Onkologie 1994;17:428-432.

“…However, p2m determina tions are thought to be extremely useful for assessing the prognosis and response to therapy of patients with lymphopro liférative disorders [2]. In this respect, the results of Poley et al [3] as published in the last issue of ONKOLOGIE are of great importance for the staging, treatment and outcome of patients. The study com prised 81 healthy subjects and some 160 patients suffering from the above-mentioned diseases.…”