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

Bradwell, Arthur R.; Harding, Stephen; Fourrier, N; Wallis, Gregg; Drayson, Mark T.; Carr-Smith, Hugh; Mead, Graham P.

doi:10.1373/clinchem.2009.123828

Cited by 116 publications

(114 citation statements)

References 19 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Ludwig

Milosavljevic

Berlanga³

et al. 2016

American J Hematol

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Heavy light chain (HLC) assays allow precise measurement of the monoclonal and of the noninvolved polyclonal immunoglobulins of the same isotype as the M‐protein (e.g., monoclonal IgAκ and polyclonal IgAλ in case of an IgAκ myeloma), which was not possible before. The noninvolved polyclonal immunoglobulin is termed ‘HLC‐matched pair’. We investigated the impact of the suppression of the HLC‐matched pair on outcome in 203 patients with multiple myeloma, a phenomenon that likely reflects the host's attempt to control the myeloma clone. Severe (>50%) HLC‐matched pair suppression was identified in 54.5% of the 156 newly diagnosed patients and was associated with significantly shorter survival (45.4 vs. 71.9 months, P = 0.019). This correlation was statistically significant in IgG patients (46.4 vs. 105.1 months, P = 0.017), but not in patients with IgA myelomas (32.9 vs. 54.1 months, P = 0.498). At best response, HLC‐matched pair suppression improved only in patients with ≥VGPR, indicating partial or complete humoral immune reconstitution during remission in those with excellent response. Severe HLC‐matched pair suppression retained its prognostic impact also during follow‐up after first response. In the 47 pretreated patients with relapsed/refractory disease, a similar correlation between severe HLC suppression and survival was noted (22.8 vs. not reached, P = 0.028). Suppression of the polyclonal immunoglobulins of the other isotypes than the myeloma protein correlated neither with HLC‐matched pair suppression, nor with outcome. Multivariate analysis identified severe HLC‐matched pair suppression as independent risk factor for shorter survival, highlighting the impact of isotype specific immune dysregulation on outcome in multiple myeloma. Am. J. Hematol. 91:295–301, 2016. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

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

Ludwig

Milosavljevic

Berlanga³

et al. 2016

American J Hematol

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“…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.…”

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confidence: 99%

“…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].…”

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confidence: 99%

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

Kraj¹

2014

Adv Clin Exp Med

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Immunofixation (IFE) is a standard method for detecting monoclonal immunoglobulins and characterizing its isotype. Recently clonality can also be determined by using immunoglobulin (Ig) heavy chain/light chain immunoassays -HLC, Hevylite TM . HLC separately measures in pairs light chain types of each intact Ig class generating ratios of monoclonal Ig/uninvolved polyclonal Ig concentrations. Studies have shown that HLC and IFE are complementary methods. HLC assays quantify monoclonal proteins and identify monoclonality. It is possible to predict prognosis in multiple myeloma and to monitor response to treatment using HLC ratio. HLC ratio may serve as a parameter for myeloma induced immunoparesis and serve as a new marker for validating remission depth and relapse probabilities (Adv Clin Exp Med 2014, 23, 1, 127-133).

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“…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.…”

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confidence: 99%

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

Katzmann

Rajkumar

2013

Leukemia

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

Cited by 116 publications

References 19 publications

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

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

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

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

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