Selection of Patients with Monoclonal Grammopathy of Undetermined Significance is Mandatory for a Reliable Use of lnterleukin-6 and Other Nonspecific Multiple Myeloma Serum Markers

Abstract

Serum levels of various immunochémical markers of clinical interest, as interleukin-6 (IL-6), C-reactive protein (CRP) and β₂-microglobulin (β₂M), were measured in sera from 98 subjects affected with monoclonal gammopathy of undetermined significance (MGUS; 80% of which bearing cancer too) and from 39 patients with multiple myeloma (MM). In addition, the ratio between serum IgG/IgA amounts (GAR) was also calculated in monoclonal gammopathies of IgG type. Consistent with our previous investigations, we found that tumor presence significantly influenced the serum levels of the various markers (except GAR) in MGUS patients; in fact, only when comparing MGUS without tumor and MM patients, was a clear difference observed for all markers considered. The data presented discourage the use of IL-6, CRP and β₂M as discriminant indices between MGUS and MM patients, unless a careful selection of MGUS subjects is performed. Further investigations on these potential markers are therefore needed for a more rational clinical application.

Serum interleukin‐6 has no discriminatory role in paraproteinaemia nor a prognostic role in multiple myeloma

“…In most published studies on paraproteinaemia the absence of clinical evidence for a haematological malignancy has been accepted as a de®nition of MGUS. Greco et al (1994) have already demonstrated the importance of clearly de®ning patients with MGUS because the presence of a solid tumour markedly in¯uenced the serum levels of IL-6, CRP and b2M in patients with paraproteinaemia who were diagnosed as`MGUS', which we also showed.…”

“…The patients were either treatment-naive, had received treatment before or were undergoing treatment when serum IL-6 was measured. Secondly, cut-off values for the upper normal IL-6 level in serum were either not given (Brown et al, 1991;Thaler et al, 1994;Greco et al, 1994;Kyrtsonis et al, 1996) or ranged widely from 3´2 pg/ml (Pelliniemi et al, 1995) to 3300 pg/ml (Tienhaara et al, 1994). Each study reported a different range of values, even for normal controls (Table III).…”