Protein electrophoresis, immunoelectrophoresis and immunofixation electrophoresis as predictors for high‐risk phenotype in familial Waldenström macroglobulinemia

Abstract

Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal gammopathy (MG) conditions such as Waldenstr€ om macroglobulinemia (WM). Immunofixation electrophoresis (IFE) is currently the most common method for isotyping of monoclonal gammopathy because of its superior sensitivity relative to immunoelectrophoresis (IEP). We designed a study to evaluate the clinicobiological relevance of small monoclonal bands detected by serum protein electrophoresis, IEP, and IFE. Serum protein electrophoresis, IEP, and IFE were used to evaluate possible monoclonal gammopathy in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of WM. IFE identified small monoclonal bands initially missed by IEP in 5 individuals (2 blood relatives, 3 spouses) among 46 study participants. All bands were IgM type. Twenty-three individuals, including the 2 blood relatives and 2 of 3 spouses with monoclonal gammopathy, were then followed for a median of 17 years (range, 13-25). The monoclonal gammopathy progressed in the 2 relatives but disappeared in the spouses, and new IgM MG developed in 2 additional relatives with a prior history of IgM polyclonal gammopathy. Small monoclonal bands detected by IFE in a familial context may be biologically meaningful, both as phenotypic biomarkers and possibly as predictors of high risk for WM. Polyclonal IgM may also be a marker of genetic susceptibility in WM families. Larger studies are needed to confirm these observations. ' 2007 Wiley-Liss, Inc.Key words: Waldenstr€ om; monoclonal gammopathy; MGUS; electrophoresis Waldenstr€ om macroglobulinemia (WM) is a chronic lymphoproliferative disorder characterized by aberrant production of monoclonal immunoglobulin type M (IgM) in the setting of histological evidence of lymphoid malignancy, most commonly lymphoplasmacytic lymphoma.1 Although rare, familial clustering of WM is known to occur.2 In family studies, the ability to identify those individuals at high risk for cancer is desirable so that genetic analyses can be performed optimally.3 Apart from certain dysmorphic syndromes that confer increased risk for cancer (e.g., Fanconi anemia), few familial hematolymphopoietic cancer syndromes have phenotypic markers associated with cancer risk.Serum protein electrophoresis followed by immunoelectrophoresis (IEP) or immunofixation electrophoresis (IFE) is integral to the recognition, diagnosis and clinical follow-up of WM.4 Methods to identify and type abnormal bands have evolved over time. Currently, IFE is the most common method for the detection and isotyping of monoclonal bands. 5,6 IFE is more sensitive than IEP 7 for the detection of small monoclonal bands, but the clinical and biological significance of these small bands is unclear. 5 Family studies in WM have identified a relatively high frequency of IgM monoclonal gammopathy (IgM MG) among relatives of WM patients.2 However, many questions remain regarding this finding, including whether small monoclonal bands have pathobiological significa...

Incidence, prevalence, mortality, and causes of death in Waldenström macroglobulinemia: a nationwide, population-based cohort study

“…These results are also supported by the fact that the prevalence of IgM-monoclonal gammopathy of undetermined significance (MGUS), which is a precursor state to WM, is lower in the Asian population than in the other races [15,16]. Furthermore, genetic predisposition, and immunologic factors in the pathogenesis of WM might be the reason behind these low incidence rates [17][18][19][20][21]. Although Korea may indeed have lower incidence, it should be noted that direct comparison with these studies may not be feasible.…”

Novel Aspects Pertaining to the Relationship of Waldenström's Macroglobulinemia, IgM Monoclonal Gammopathy of Undetermined Significance, Polyclonal Gammopathy, and Hypoglobulinemia

“…We have found that serum immunofixation electrophoresis (IFE) is a sensitive technique for identifying at-risk individuals within families 21. While serum IFE detected small-volume IgM monoclonal bands, that were below the detection limit with immunoelectrophoresis, in both relatives and unrelated individuals, serial serum IFE demonstrated that the monoclonal bands persisted only in relatives of WM patients.…”

Differential characteristics of Waldenström macroglobulinemia according to patterns of familial aggregation

“…Mounting evidence suggests that WM coaggregates and may share risk factors with other B-cell disorders 20 and that IgM-MGUS is a precursor condition for WM. 5,[24][25][26] In our analysis, we included 28 relatives who had a history of a non-WM B-cell disorder or MGUS and who completed questionnaires (see "Data collection") with the unaffected group. However, a sensitivity analysis based on excluding these 28 persons from the control group did not change the results (data not shown).…”