MASS‐FIX may allow identification of patients at risk for light chain amyloidosis before the onset of symptoms

Kourelis, Taxiarchis; Murray, David; Dasari, Surendra; Kumar, Sanjay; Barnidge, David R.; Madden, Benjamin J.; Arendt, Bonnie K.; Milani, Paolo; Merlini, Giampaolo; Ramı́rez-Alvarado, Marina; Kyle, Robert A.; Dispenzieri, Angela

doi:10.1002/ajh.25244

Cited by 37 publications

(22 citation statements)

References 7 publications

(8 reference statements)

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“… 2 We demonstrated previously that monoclonal LCs of patients with kappa restricted immunoglobulin light chain amyloidosis (AL) are N-glycosylated at a rate nearly 13-fold higher than the kappa LCs of patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and assorted plasma cell disorders (PCDs) 3 , 4 and that N-glycosylation of monoclonal LCs starts at the MGUS stage, predating the diagnosis of AL amyloidosis by years to decades. 5 …”

Section: Introductionmentioning

confidence: 99%

N-glycosylation of monoclonal light chains on routine MASS-FIX testing is a risk factor for MGUS progression

et al. 2020

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Our group previously demonstrated that M-protein light chain (LC) glycosylation can be detected on routine MASS-FIX testing. Glycosylation is increased in patients with immunoglobulin light chain amyloidosis (AL) and rarely changes over the course of a patient’s lifetime. To determine the rates of progression to AL and other plasma cell disorders (PCDs), we used residual serum samples from the Olmsted monoclonal gammopathy of undetermined significance (MGUS) screening cohort. Four-hundred and fourteen patients with known MGUS were tested by MASS-FIX, and 25 (6%) were found to have glycosylated light chains (LCs). With a median follow-up of surviving patients of 22.2 years, the 20-year progression rates to a malignant PCD were 67% (95% CI 29%, 84%) and 13% (95% CI 9%, 18%) for patients with and without glycosylated LCs, respectively. The risk of progression was independent of Mayo MGUS risk score. The respective rates of progression to AL at 20-years were 21% (95% CI 0.0, 38%) and 3% (95% CI 0.6%, 5.5%). In summary, monoclonal LC glycosylation is a potent risk factor for progression to AL, myeloma, and other PCDs, an observation which could lead to earlier diagnoses and potentially reduced morbidity and mortality.

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Section: Introductionmentioning

confidence: 99%

N-glycosylation of monoclonal light chains on routine MASS-FIX testing is a risk factor for MGUS progression

et al. 2020

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“…LC N-glycosylation has diagnostic implications, as it is more common in immunoglobulin light chain (AL) amyloidosis and cold agglutinin disease (CAD) compared to other plasma cell disorders (PCD) 5,6 . In AL amyloidosis, LC N-glycosylation is present from the time of diagnosis of monoclonal gammopathy of undetermined significance (MGUS), and represents an independent risk factor for progression of MGUS to AL amyloidosis and other PCD 7,8 . Moreover, LC N-glycosylation has been implicated in the pathogenesis of amyloid fibril formation in AL amyloidosis 9 .…”

Section: Introductionmentioning

confidence: 99%

MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients

et al. 2021

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Immunoenrichment-based matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), termed MASS-FIX, offers several advantages over immunofixation for the detection and isotyping of serum monoclonal protein, including superior sensitivity and specificity, the ability to differentiate therapeutic monoclonal antibodies, and the rapid identification of light chain (LC) N-glycosylation. We identified 6315 patients with MASS-FIX performed at our institution since 2018. Of these, 4118 patients (65%) with a wide array of plasma cell disorders (PCD), including rare monoclonal gammopathies of clinical significance, had a positive MASS-FIX. Two-hundred twenty-one (5%) of the MASS-FIX positive patients had evidence of LC N-glycosylation, which was more commonly identified in IgM heavy chain isotype, kappa LC isotype, and in diagnoses of immunoglobulin light chain (AL) amyloidosis and cold agglutinin disease (CAD) compared to other PCD. This cross-sectional study describes the largest cohort of patients to undergo MASS-FIX in routine clinical practice. Our findings demonstrate the widespread utility of this assay, and confirm that LC N-glycosylation should prompt suspicion for AL amyloidosis and CAD in the appropriate clinical context.

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“…Interestingly, LC glycosylation was also found to be an independent risk factor for the progression of MGUS to myeloma and related disorders 39 . These glycosylated LCs were demonstrated to be present years before the diagnosis of myeloma of related disorder and hence may allow for identification of patients at higher risk for PCDs 40 .…”

Section: Analytical and Clinical Performance Of Intact Lc Maldi-tof Amentioning

confidence: 99%

Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report

et al. 2021

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Plasma cell disorders (PCDs) are identified in the clinical lab by detecting the monoclonal immunoglobulin (M-protein) which they produce. Traditionally, serum protein electrophoresis methods have been utilized to detect and isotype M-proteins. Increasing demands to detect low-level disease and new therapeutic monoclonal immunoglobulin treatments have stretched the electrophoretic methods to their analytical limits. Newer techniques based on mass spectrometry (MS) are emerging which have improved clinical and analytical performance. MS is gaining traction into clinical laboratories, and has replaced immunofixation electrophoresis (IFE) in routine practice at one institution. The International Myeloma Working Group (IMWG) Mass Spectrometry Committee reviewed the literature in order to summarize current data and to make recommendations regarding the role of mass spectrometric methods in diagnosing and monitoring patients with myeloma and related disorders. Current literature demonstrates that immune-enrichment of immunoglobulins coupled to intact light chain MALDI-TOF MS has clinical characteristics equivalent in performance to IFE with added benefits of detecting additional risk factors for PCDs, differentiating M-protein from therapeutic antibodies, and is a suitable replacement for IFE for diagnosing and monitoring multiple myeloma and related PCDs. In this paper we discuss the IMWG recommendations for the use of MS in PCDs.

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MASS‐FIX may allow identification of patients at risk for light chain amyloidosis before the onset of symptoms

Cited by 37 publications

References 7 publications

N-glycosylation of monoclonal light chains on routine MASS-FIX testing is a risk factor for MGUS progression

N-glycosylation of monoclonal light chains on routine MASS-FIX testing is a risk factor for MGUS progression

MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients

Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report

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