Prevalence and progression of monoclonal gammopathy of undetermined significance and light-chain MGUS in Germany

Abstract

We determined the prevalence and progression rate of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS (LCMGUS) in Germany utilizing the biobank of the population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45-75 years. To detect monoclonal proteins, standard serum electrophoresis was combined with parallel screening immunofixation using pentavalent antisera. Additionally, free light chains (FLC) were measured in all samples. Definition of MGUS included M-protein concentration, laboratory results, and disease history. LCMGUS was defined as abnormal FLC ratio, increase in FLC causing the abnormal ratio, and lack of intact immunoglobulin. One hundred sixty-five MGUS cases were identified among 4,702 screened samples (prevalence 3.5%, 95% confidence interval (CI) 3.0-4.1; median age 63 years, range 47-75 years; 103 (62%) male; IgG 59%, IgA 17%, IgM 17%, biclonal 4.8%, kappa 56%, and lambda 44%). Five cases progressed (0.6%/year, 95% CI 0.2-1.4). An abnormal FLC ratio was detected in 220 samples. Thirty-nine of these showed intact immunoglobulin. Thirty-four of the remaining met LCMGUS criteria (prevalence 0.7%, 95% CI 0.5-1.0). None of the LCMGUS cases progressed. We demonstrate a MGUS prevalence of 3.5% and a LCMGUS prevalence of 0.7% in the general population aged 45-75 years in Germany using a sensitive screening approach.

Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point

“…The reported population prevalences detected by sIFE and conventional diagnostic approaches do not suggest that sIFE will result in a gross over-diagnosis of MGUS with very small paraproteins. The rate in individuals older than 40 years of 3.5% (95% CI 3.0%-4.1%) identified with sIFE was not significantly different from the 3.2% (95% CI 3.0%-3.5%) identified by conventional practice in individuals older than 50 years (χ 2 = 0.828, p = 0.36) [1,6]. The difference remained statistically insignificant when only individuals above 50 years were considered (χ 2 = 3.55, p = 0.06).…”

“…The principle is graphically illustrated in Figure 1 where samples were applied in an identical sequence on a standard PE and a sIFE gel. In the sera of newly investigated patients sIFE detected 22.1%±6.7% (95% CI) and 27.3%±6.7% of paraproteins that were not identified with PE [1,2]. Approximately half of these paraproteins migrated in the β region and typed as IgA, IgM or as free light chains [2] that are recognised to confer a higher risk of progression than those with IgG subtypes [12].…”

“…In two well-conducted population-based series MGUS was detected in 3.2% of individuals older than 50 years and in 3.5% of individuals older than 40, respectively [1,6]. The reported population prevalence of myeloma demonstrates geographic variability ranging from 0.020% in the UK (circa 2012), 0.026% in Australia (circa 2007) and 0.029% in the USA (circa 2012) [7][8][9].…”

“…This leverages the improved analytical sensitivity and specificity of immune typing techniques and approaches the efficiency of standard electrophoretic techniques [1,2]. The principle is graphically illustrated in Figure 1 where samples were applied in an identical sequence on a standard PE and a sIFE gel.…”

“…Screening immunofixation electrophoresis (sIFE) is a modified immunofixation (IFE) procedure that employs a single application of combined antisera directed against heavy and/or light chains to detect a paraprotein. The technical aspects and diagnostic performance of sIFE is dealt with in detail elsewhere [1,2]. The clinical rationale behind detecting small paraproteins and the analytical characteristics of the available procedures will be briefly discussed to justify the recommendation that sIFE should be the initial laboratory procedure to investigate paraproteins in complex serum and urine matrices.…”