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Monoclonal Gammopathy of Undetermined Significance

Immunology · NLM MeSH · updated 2026-10-29 · version 1

Citations verified against PubMedNot yet clinician-reviewed10 referencesApproximately 4 min read

Conditions characterized by the presence of M protein (Monoclonal protein) in serum or urine without clinical manifestations of plasma cell dyscrasia.

Table of Contents

1. Definition2. Research landscape3. Reading the evidence4. Open-access studies5. Key reviews6. References7. About this article

Definition and research guide

This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.

Content available: 4 complete abstracts (843 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.

Definition

Conditions characterized by the presence of M protein (Monoclonal protein) in serum or urine without clinical manifestations of plasma cell dyscrasia.

Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.

Also known as: Benign Monoclonal Gammopathies; Benign Monoclonal Gammopathy; Monoclonal Gammopathy, Benign; Monoclonal Gammopathies, Benign; Monoclonal Gammapathies, Benign; Benign Monoclonal Gammapathies; Benign Monoclonal Gammapathy; Monoclonal Gammapathy, Benign.

Where it fits in the MeSH classification

Broader topics
Hypergammaglobulinemia; Paraproteinemias
Narrower topics
Schnitzler Syndrome

Research landscape

PubMed indexes 2,119 records tagged with the MeSH heading “Monoclonal Gammopathy of Undetermined Significance” (counts retrieved 2026-10-29). 723 of them (34.1%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 886 records.

Reviews account for 437 records (20.6%) and meta-analyses for 9. Randomized controlled trials number 11 (0.5%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.

PubMed records by publication periodthrough 1999: 268 records; 2000-2009: 242 records; 2010-2019: 886 records; 2020 onward: 723 records268through 19992422000-20098862010-20197232020 onward
Records in PubMed indexed with this heading, by publication period. Real counts from NCBI E-utilities; the final period covers only part of the current year. Volume reflects how much has been published, not how strong the evidence is.
Show the data
PeriodRecords
through 1999268
2000-2009242
2010-2019886
2020 onward723
Share of records by publication typeReviews: 20.6 percent; Meta-analyses: 0.4 percent; Randomized controlled trials: 0.5 percentReviews20.6% (437)Meta-analyses0.4% (9)Randomized controlled trials0.5% (11)
Share of all PubMed records on this heading that carry each publication type. Types overlap with other records, so the shares do not sum to 100%.
Publication-type chart data
Publication types among 2,119 PubMed records
TypeRecordsShare
Reviews43720.6%
Meta-analyses90.4%
Randomized controlled trials110.5%

Method: PubMed query "Monoclonal Gammopathy of Undetermined Significance"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.

Reading the evidence in immunology

Immune responses are studied in model organisms, in cells from donors and in patients, and the same pathway can behave differently across these settings. Mouse immune systems differ from human ones in important ways, and blood measurements may not reflect what happens in tissues. Clinical conclusions about immune-mediated disease or immunotherapy come mainly from controlled trials and long-term cohorts. Check the species and tissue studied, whether markers were linked to outcomes patients notice, and the follow-up time.

Evidence from open-access studies

These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.

Study comparison — selected abstracts, not a systematic review
Study / authorsYearSource label / designEurope PMC citationsLicence / source
Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies
Rögnvaldsson S, Love TJ, Thorsteinsdottir S, Reed ER, Óskarsson JÞ, Pétursdóttir Í, et al.
2021Randomized controlled trial
Design not recorded in structured metadata
110cc by
PMID 34001889 · DOI · PMC8128921
Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12372 individuals 10-49 years old: a population-based study from the National Health and Nutrition Examination Survey
Landgren O, Graubard BI, Kumar S, Kyle RA, Katzmann JA, Murata K, et al.
2017Research article
Design not recorded in structured metadata
96cc by
PMID 29053158 · DOI · PMC5678222
Detection and prevalence of monoclonal gammopathy of undetermined significance: a study utilizing mass spectrometry-based monoclonal immunoglobulin rapid accurate mass measurement
Murray D, Kumar SK, Kyle RA, Dispenzieri A, Dasari S, Larson DR, et al.
2019Research article
Design not recorded in structured metadata
83cc by
PMID 31836698 · DOI · PMC6910906
CIDP With and Without Monoclonal Gammopathy of Undetermined Significance (MGUS): Comparison of Clinical Phenotype, Diagnostic Features, and Treatment Response
van Veen R, Baars AE, van Doorn IN, Michael M, Bus SRM, Broers MC, et al.
2026Research article
Design not recorded in structured metadata
1cc by
PMID 41819123 · DOI · PMC12981947

Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies [1]

Randomized controlled trial Rögnvaldsson S, Love TJ, Thorsteinsdottir S, Reed ER, Óskarsson JÞ, Pétursdóttir Í, et al. · · 2021 · cited 110 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM).
Closing excerpt
The study can lead to a paradigm shift in MM therapy towards screening and early therapy.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (199 words)

Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34001889 · DOI · PMC8128921

Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12372 individuals 10-49 years old: a population-based study from the National Health and Nutrition Examination Survey [2]

Research article Landgren O, Graubard BI, Kumar S, Kyle RA, Katzmann JA, Murata K, et al. · · 2017 · cited 96 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10-49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III.
Closing excerpt
In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (195 words)

We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10-49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III. NHANES prevalence rates were standardized to the 2000 US total population. Among 12 372 individuals (4073 blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified in 63 persons (0.34%, 95% CI 0.23-0.50). The prevalence of MGUS was significantly higher in blacks (0.88%, 95% CI 0.62-1.26) compared with whites (0.22%, 95% CI 0.11-0.45), P=0.001. The prevalence of MGUS in Mexican-Americans was at an intermediate level (0.41%, 95% CI 0.23-0.73). The disparity in prevalence of MGUS between blacks and whites was most striking in the 40-49 age-group; 3.26% (95% CI 2.04-5.18) versus 0.53% (95% CI 0.20-1.37), P=0.0013. There was a trend to earlier age of onset of MGUS in blacks compared with whites. MGUS was seen in only two persons in the 10-19 age-group (both Mexican-American), and in three persons in the 20-29-year age-group (all of whom were black). In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29053158 · DOI · PMC5678222

Detection and prevalence of monoclonal gammopathy of undetermined significance: a study utilizing mass spectrometry-based monoclonal immunoglobulin rapid accurate mass measurement [3]

Research article Murray D, Kumar SK, Kyle RA, Dispenzieri A, Dasari S, Larson DR, et al. · · 2019 · cited 83 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
High-sensitivity mass spectrometry assays are available to detect monoclonal immunoglobulins.
Closing excerpt
This represents the most accurate prevalence estimate of MGUS thus far.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (190 words)

High-sensitivity mass spectrometry assays are available to detect monoclonal immunoglobulins. To better assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS), we identified 300 patients diagnosed with MGUS or related gammopathy who had a prior negative work-up for monoclonal proteins as part of the Olmsted County MGUS screening study. Two mass spectrometry-based detection methods (matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and monoclonal immunoglobulin rapid accurate mass measurements (miRAMM) along with traditional immunofixation were performed on the Olmsted baseline and MGUS diagnostics serum samples. Among the 226 patients considered negative for MGUS based on protein electrophoresis and serum-free light-chain assay, a monoclonal protein could be detected at baseline in 24 patients (10.6%) by immunofixation, 113 patients (50%) by MADLI-TOF mass spectrometry, and 149 patients (65.9%) by miRAMM mass spectrometry. In addition, using miRAMM, some patients demonstrated an oligoclonal to monoclonal transition giving insight into the origin of MGUS. Using the sensitive miRAMM, MGUS is present in 887 of 17,367 persons from the Olmsted County cohort, translating into a prevalence of 5.1% among persons 50 years of age and older. This represents the most accurate prevalence estimate of MGUS thus far.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31836698 · DOI · PMC6910906

CIDP With and Without Monoclonal Gammopathy of Undetermined Significance (MGUS): Comparison of Clinical Phenotype, Diagnostic Features, and Treatment Response [4]

Research article van Veen R, Baars AE, van Doorn IN, Michael M, Bus SRM, Broers MC, et al. · · 2026 · cited 1 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Background and aimsMonoclonal gammopathy of undetermined significance (MGUS) occurs in some patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but its impact on clinical phenotype and treatment response remains unclear.
Closing excerpt
These findings indicate that, although IgG MGUS is associated with CIDP, the presence of IgG MGUS does not constitute a distinct subgroup with unique clinical features or treatment implications.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (259 words)

Background and aimsMonoclonal gammopathy of undetermined significance (MGUS) occurs in some patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but its impact on clinical phenotype and treatment response remains unclear. We assessed the prevalence of paraproteinemia in CIDP and compared disease features between CIDP patients with and without MGUS.MethodsWe used data from the International CIDP Outcome Study (ICOS), a prospective cohort study. We compared the prevalence and causes of paraproteinemia in CIDP to matched disease controls (axonal polyneuropathy or motor neuron disease) and compared disease features and treatment responses between CIDP patients with and without MGUS. Treatment response, defined as a ≥ 1-point improvement on the modified Rankin scale, was retrospectively assessed.ResultsIgG paraproteinemia was more common in CIDP than in controls (9%, 17/193 vs. 3%, 6/192; p = 0.03). IgM and IgA paraprotein prevalences did not differ. One CIDP patient had Waldenström macroglobulinemia; others had MGUS. Patients with IgG MGUS less often had an acute clinical presentation (6% vs. 33%; p = 0.02), more often had sensory deficits (94% vs. 67%; p = 0.02), and prolonged distal CMAP duration (64% vs. 31%; p = 0.02), compared to patients without MGUS. First-line treatment response rates were comparable (80% [IgG MGUS] vs. 67% [no MGUS]; p = 0.39).InterpretationIgG MGUS is more prevalent in CIDP than in controls. Presence of IgG MGUS is weakly associated with some CIDP disease features, but not treatment response. These findings indicate that, although IgG MGUS is associated with CIDP, the presence of IgG MGUS does not constitute a distinct subgroup with unique clinical features or treatment implications.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41819123 · DOI · PMC12981947

Key reviews and meta-analyses

The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.

  • Research article Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management [5]
    Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al. · Leukemia · 2010 · cited 603 times (Europe PMC)
  • Research article Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant [6]
    Leung N, Bridoux F, Hutchison CA, Nasr SH, Cockwell P, Fermand JP, et al. · Blood · 2012 · cited 373 times (Europe PMC)
  • Research article Targeting the bone marrow microenvironment in multiple myeloma [7]
    Kawano Y, Moschetta M, Manier S, Glavey S, Görgün GT, Roccaro AM, et al. · Immunol Rev · 2015 · cited 333 times (Europe PMC)
  • Research article Diagnosis of monoclonal gammopathy of renal significance [8]
    Bridoux F, Leung N, Hutchison CA, Touchard G, Sethi S, Fermand JP, et al. · Kidney Int · 2015 · cited 288 times (Europe PMC)
  • Research article Molecular pathogenesis of multiple myeloma and its premalignant precursor [9]
    Kuehl WM, Bergsagel PL · J Clin Invest · 2012 · cited 261 times (Europe PMC)
  • Research article The multiple myelomas - current concepts in cytogenetic classification and therapy [10]
    Kumar SK, Rajkumar SV · Nat Rev Clin Oncol · 2018 · cited 255 times (Europe PMC)

References

  1. Rögnvaldsson S, Love TJ, Thorsteinsdottir S, Reed ER, Óskarsson JÞ, Pétursdóttir Í, et al.. Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies. . 2021. PMID 34001889 · DOI · PMC8128921
  2. Landgren O, Graubard BI, Kumar S, Kyle RA, Katzmann JA, Murata K, et al.. Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12372 individuals 10-49 years old: a population-based study from the National Health and Nutrition Examination Survey. . 2017. PMID 29053158 · DOI · PMC5678222
  3. Murray D, Kumar SK, Kyle RA, Dispenzieri A, Dasari S, Larson DR, et al.. Detection and prevalence of monoclonal gammopathy of undetermined significance: a study utilizing mass spectrometry-based monoclonal immunoglobulin rapid accurate mass measurement. . 2019. PMID 31836698 · DOI · PMC6910906
  4. van Veen R, Baars AE, van Doorn IN, Michael M, Bus SRM, Broers MC, et al.. CIDP With and Without Monoclonal Gammopathy of Undetermined Significance (MGUS): Comparison of Clinical Phenotype, Diagnostic Features, and Treatment Response. . 2026. PMID 41819123 · DOI · PMC12981947
  5. Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al.. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010. PMID 20410922 · DOI · PMC7020664
  6. Leung N, Bridoux F, Hutchison CA, Nasr SH, Cockwell P, Fermand JP, et al.. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant. Blood. 2012. PMID 23047823 · DOI
  7. Kawano Y, Moschetta M, Manier S, Glavey S, Görgün GT, Roccaro AM, et al.. Targeting the bone marrow microenvironment in multiple myeloma. Immunol Rev. 2015. PMID 25510276 · DOI
  8. Bridoux F, Leung N, Hutchison CA, Touchard G, Sethi S, Fermand JP, et al.. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015. PMID 25607108 · DOI
  9. Kuehl WM, Bergsagel PL. Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest. 2012. PMID 23023717 · DOI · PMC3461901
  10. Kumar SK, Rajkumar SV. The multiple myelomas - current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol. 2018. PMID 29686421 · DOI

About this article

Sources
NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
Verification
Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
Review state
automated source verified; no human expert review has been recorded yet.
Version
1, last updated 2026-10-29.

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Related research topics

  • Heavy Chain DiseaseImmunology
  • CryoglobulinemiaCardiovascular Medicine
  • Multiple MyelomaCancer and Oncology
  • Waldenstrom MacroglobulinemiaCancer and Oncology
  • AgammaglobulinemiaImmunology
  • Schnitzler SyndromeImmunology

All 90 articles in Immunology →

At a glance

2,119
PubMed records on this heading
34%
published since 2020
437
review articles
11
randomized trials
10
verified references below

Counts come from PubMed on 2026-10-29; they show how much has been written, not how strong the evidence is.

Related topics See all →

  • Heavy Chain DiseaseImmunology
  • CryoglobulinemiaCardiovascular Medicine
  • Multiple MyelomaCancer and Oncology
  • Waldenstrom MacroglobulinemiaCancer and Oncology
  • AgammaglobulinemiaImmunology

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