Assessment of Monoclonal Gammopathies by Nephelometric Measurement of Individual Immunoglobulin κ/λ Ratios

Abstract

BACKGROUND:Currently, monoclonal immunoglobulins are identified and quantified from bands on electrophoretic gels. As an alternative, clonality might be determined by measuring the separate light chain types of each Ig class to allow numerical assessment of IgЈ/ IgЈ ratios, analogous to free light chain / ratios.

Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma

“…Signs of severe immunosuppression, such as impairment of polyclonal B‐cell progenitors and plasma cell precursors 1 and suppression of uninvolved polyclonal immunoglobulins of a different isotype to the tumor monoclonal protein are frequently observed in patients with multiple myeloma and have been associated with adverse prognosis 2 while preserved polyclonal B cell proliferation and immunoglobulin synthesis usually is associated with favorable prognosis 3. The recently developed HLC assay allows the measurement of both pairs of a specific isotype, e.g., quantification of IgAλ and of IgAκ in a patient with IgAλ monoclonal gammopathy 4, 5. Thereby a ratio between involved and noninvolved HLC‐matched pairs similar to the FLC ratio can be calculated.…”

Immunoglobulin Heavy Chain/Light Chain Pairs (Hlc, Hevylitetm) Assays for Diagnosing and Monitoring Monoclonal Gammopathies

“…In 2009 Bradwell et al [6] developed immunoglobulin heavy/light chain immunoassays -"Hevylite" (HLC). Availability of antibodies which bind to conformational epitopes spanning the junctional regions between bound κ or λ light chains and their respective heavy chain partners has allowed the specific measurement of serum IgGκ, IgGλ, IgAκ, IgAλ, IgMκ and IgMλ concentrations (Fig.…”

“…Bradwell et al [6] proved that use of anti -HLC reagents could help in the vexing issue of detecting and providing reproducible measurements of M proteins that comigrate with other major serum components, such as transferrin or C3. Normal concentration ranges of HLC immunoglobulins and HLC ratios in blood donors sera are shown in Table 1 [6].…”

“…Normal concentration ranges of HLC immunoglobulins and HLC ratios in blood donors sera are shown in Table 1 [6].…”

A window into immunoglobulin quantitation and plasma cell disease: antigen epitopes defined by the junction of immunoglobulin heavy and light chains

“…12 This assay (Hevylite; The Binding Site, Birmingham, UK) separately quantitates IgGk, IgGl, IgAk, IgAl, IgMk and/or IgMl. The quantitation of Igs by isotype-specific light chains allows the same approaches as have been used for FLCs, that is, the ratio of the HLC pairs (for example, IgGk/IgGl) may provide diagnostic information regarding clonal proliferation, and ratios plus quantitation of individual HLC can aid in disease monitoring.…”