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Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

ABSTRACT: Response criteria for multiple myeloma are based upon changes in monoclonal protein levels quantified using serum and/or urine protein electrophoresis. The latter lacks sensitivity at low monoclonal protein levels and since 2001, the serum free light chain test has been available and its clinical utility proven, yet guidelines have not recommended it as a replacement for urine assessment. Herein we evaluated responses using serum free light chain measurements and serum and urine electrophoresis after 2 and 4 cycles of therapy and after stem cell transplantation in 25 light chain and 157 intact immunoglobulin myeloma patients enrolled in the IFM 2007-02 MM trial. All 25 light chain patients had measurable disease by serum free light chain and urine methods at presentation. By contrast 98 out of 157 intact immunoglobulin patients had measurable disease by serum free light chain compared to 55 out of 157 by urine electrophoresis. In all patients there was substantial agreement between predicate (serum/urine protein electrophoresis) and test (serum protein electrophoresis and serum free light chain) methods for response assessment (Weighted Kappa=0.83). Urine immunofixation became negative in 47% light chain and 43% intact immunoglobulin patients after 2 cycles of therapy. At this time the serum free light chain ratio normalised in only 11% and 27% patients, respectively. In summary we found good agreement between methods for response assessment, but the serum free light chain test provided greater sensitivity than urine electrophoresis for monitoring. To our knowledge this is the first report comparing both methods for response assignment based on the International Myeloma Working Group guidelines. (Clinical Trials Register.eu identifier: 2007-005204-40).

SUBMITTER: Dejoie T

PROVIDER: S-EPMC4815727 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

Dejoie Thomas T Attal Michel M Moreau Philippe P Harousseau Jean-Luc JL Avet-Loiseau Herve H

Haematologica 20151203 3

Response criteria for multiple myeloma are based upon changes in monoclonal protein levels quantified using serum and/or urine protein electrophoresis. The latter lacks sensitivity at low monoclonal protein levels and since 2001, the serum free light chain test has been available and its clinical utility proven, yet guidelines have not recommended it as a replacement for urine assessment. Herein we evaluated responses using serum free light chain measurements and serum and urine electrophoresis ...[more]

PMID: 26635032

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Project description:Mass spectrometry (MS) has become an indispensable tool in structural characterization and quality control of monoclonal antibodies (mAbs). Intact-mass analysis is a particularly attractive option that provides a powerful and cost-effective means to not only confirm the structural integrity of the protein, but also probe its interactions with therapeutic targets. To a certain extent, this success can be attributed to relatively modest glycosylation levels exhibited by IgG molecules, which limits their structural heterogeneity and enables straightforward mass measurements at the intact molecule level. The recent surge of interest in expanding the repertoire of mAbs to include other classes of immunoglobulins places a premium on efforts to adapt the IgG-tailored experimental strategies to other classes of antibodies, but their dramatically higher levels of glycosylation may create insurmountable obstacles. The monoclonal murine IgE antibody explored in this work provides a challenging model system, as its glycosylation level exceeds that of conventional IgG mAbs by a factor of nine. The commercial sample, which included various IgE fragments, yields a poorly resolved ionic signal in intact-mass measurements, from which little useful information can be extracted. However, coupling MS measurements with the limited charge reduction of select polycationic species in the gas phase gives rise to well-defined charge ladders, from which both ionic masses and charges can be readily determined. The measurements reveal significant variation of the extent of glycosylation within intact IgE molecules, as well as the presence of low-molecular weight impurities in the commercial IgE sample. Furthermore, incubation of the monoclonal IgE with its antigen (ovalbumin) gives rise to the formation of complexes with varying stoichiometries, which can also be uniquely identified using a combination of native MS, limited charge reduction in the gas phase and data fitting procedures. This work demonstrates that following appropriate modifications, intact-mass analysis measurements can be successfully applied to mAbs beyond the IgG isotype, providing a wealth of information not only on the mass distribution of the intact IgE molecules, but also their large-scale conformational integrity, the integrity of their covalent structure, and their interactions with antigens.

Dataset Information

Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

Publications

Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

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