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1. Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study

Author

Long, Thorir Einarsson, Indridason, Olafur Skuli, Palsson, Runolfur, Rognvaldsson, Sæmundur, Love, Thorvardur Jon, Thorsteinsdottir, Sigrun, Sverrisdottir, Ingigerdur Solveig, Vidarsson, Brynjar, Onundarson, Pall Torfi, Agnarsson, Bjarni Agnar, Sigurdardottir, Margret, Thorsteinsdottir, Ingunn, Olafsson, Isleifur, Thordardottir, Asdis Rosa, Eythorsson, Elias, Jonsson, Asbjorn, Gislason, Gauti, Olafsson, Andri, Steingrimsdottir, Hlif, Hultcrantz, Malin, Durie, Brian G. M., Harding, Stephen, Landgren, Ola, and Kristinsson, Sigurdur Yngvi

Published
2022
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2. Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study

Author

Rognvaldsson, Saemundur, Eythorsson, Elias, Thorsteinsdottir, Sigrun, Vidarsson, Brynjar, Onundarson, Pall Torfi, Agnarsson, Bjarni A., Sigurdardottir, Margret, Thorsteinsdóttir, Ingunn, Olafsson, Isleifur, Runolfsdottir, Hrafnhildur L., Helgason, Dadi, Emilsdottir, Arna R., Agustsson, Arnar S., Bjornsson, Aron H., Kristjansdottir, Gudrun, Thordardottir, Asdis Rosa, Indridason, Olafur Skuli, Jonsson, Asbjorn, Gislason, Gauti Kjartan, Olafsson, Andri, Steingrimsdottir, Hlif, Kampanis, Petros, Hultcrantz, Malin, Durie, Brian G. M., Harding, Stephen, Landgren, Ola, Palsson, Runolfur, Love, Thorvarður Jon, and Kristinsson, Sigurdur Yngvi

Published
2021
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3. Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance: An Analysis From a Population-Based Screening Study.

Author

Sverrisdottir, Ingigerdur, Thorsteinsdottir, Sigrun, Rognvaldsson, Sæmundur, Aspelund, Thor, Vidarsson, Brynjar, Onundarson, Pall Torfi, Agnarsson, Bjarni A., Sigurdardottir, Margret, Thorsteinsdóttir, Ingunn, Sveinsdottir, Signy Vala, Palmason, Robert, Olafsson, Isleifur, Sigurdsson, Fridbjorn, Thordardóttir, Asdis Rosa, Eythorsson, Elias, Jonsson, Asbjorn, Palsson, Runolfur, Indridason, Olafur Skuli, Gislason, Gauti Kjartan, and Olafsson, Andri

Subjects
MONOCLONAL gammopathies, AUTOIMMUNE diseases, MEDICAL screening, POISSON regression, MULTIPLE myeloma, DIAGNOSIS
Abstract

Prior studies suggest a possible association between autoimmune conditions and monoclonal gammopathy of undetermined significance, but these findings may reflect ascertainment bias inherent in the study design. This current study mitigates the bias by examining the association using data from a population-based screening study. Visual Abstract. Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance: Prior studies suggest a possible association between autoimmune conditions and monoclonal gammopathy of undetermined significance, but these findings may reflect ascertainment bias inherent in the study design. This current study mitigates the bias by examining the association using data from a population-based screening study. Background: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias. Objective: To examine whether MGUS is associated with autoimmune diseases. Design: A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS. Setting: Icelandic population of adults aged 40 years or older. Patients: 75 422 persons screened for MGUS. Measurements: Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex. Results: A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70]). Limitation: Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results. Conclusion: The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted. Primary Funding Source: The International Myeloma Foundation and the European Research Council. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance: A Cohort Study Nested in a Clinical Trial.

Author

Eythorsson, Elias, Rognvaldsson, Saemundur, Thorsteinsdottir, Sigrun, Einarsson Long, Thorir, Reed, Elin Ruth, Sigurdardottir, Gudrun Asta, Vidarsson, Brynjar, Onundarson, Pall Torfi, Agnarsson, Bjarni A., Sigurdardottir, Margret, Olafsson, Isleifur, Thorsteinsdottir, Ingunn, Sveinsdottir, Signy Vala, Sigurdsson, Fridbjorn, Thordardottir, Asdis Rosa, Palsson, Runolfur, Indridason, Olafur Skuli, Jonsson, Asbjorn, Gislason, Gauti Kjartan, and Olafsson, Andri

Subjects
BONE marrow, BONE marrow cells, MULTIPLE myeloma, CLINICAL trials, COHORT analysis
Abstract

Smoldering multiple myeloma is an asymptomatic precursor to multiple myeloma that has a higher risk of progression than monoclonal gammopathy of undetermined significance and may warrant closer monitoring. This study develops a new prediction model to predict the likelihood of smoldering multiple myeloma in persons with monoclonal gammopathy of undetermined significance to inform the decision to obtain a bone marrow sample and compares its performance to the Mayo Clinic risk stratification model. Visual Abstract. Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance: Smoldering multiple myeloma is an asymptomatic precursor to multiple myeloma that has a higher risk of progression than monoclonal gammopathy of undetermined significance and may warrant closer monitoring. This study develops a new prediction model to predict the likelihood of smoldering multiple myeloma in persons with monoclonal gammopathy of undetermined significance to inform the decision to obtain a bone marrow sample and compares its performance to the Mayo Clinic risk stratification model. Background: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. Objective: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model. Design: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597) Setting: Icelandic population of adults aged 40 years or older. Patients: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample. Measurements: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater. Results: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, −0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds. Limitation: The prediction model will require external validation. Conclusion: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology. Primary Funding Source: International Myeloma Foundation and the European Research Council. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Prevalence of MGUS Is High in the Istopmm Study but the Prevalence of IgA MGUS Does Not Increase with Age in the Way Other Immunoglobulin Subtypes Do

Author

Love, Thorvardur Jon, primary, Rögnvaldsson, Sæmundur, additional, Thorsteinsdottir, Sigrun, additional, Aspelund, Thor, additional, Reed, Elin Ruth, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Sveinsdottir, Signy Vala, additional, Olafsson, Isleifur, additional, Sigurdsson, Fridbjorn, additional, Thordardottir, Asdis Rosa, additional, Eythorsson, Elias, additional, Jonsson, Asbjorn, additional, Palsson, Runolfur, additional, Indridason, Olafur Skuli, additional, Gislason, Gauti, additional, Olafsson, Andri, additional, Sigurdsson, Jon Kristinn, additional, Sverrisdottir, Ingigerdur Solveig, additional, Steingrimsdottir, Hlif, additional, Einarsson Long, Thorir, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Harding, Stephen, additional, Landgren, Ola, additional, and Kristinsson, Sigurdur Y, additional

Published
2022
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6. Transient M-Proteins: Epidemiology, Causes, and the Impact of Mass Spectrometry: The Istopmm Study

Author

Palmason, Robert, primary, Berlanga, Oscar, additional, Sigurdsson, Jon Kristinn, additional, Rögnvaldsson, Sæmundur, additional, Thorsteinsdottir, Sigrun, additional, Ekberg, Sara, additional, Crowther, Michael, additional, Levy, Marina, additional, Reed, Elin Ruth, additional, Oskarsson, Jon Þórir, additional, Sigurdardottir, Gudrun Asta, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Sveinsdottir, Signy Vala, additional, Sigurdsson, Fridbjorn, additional, Olafsson, Isleifur, additional, Thordardottir, Asdis Rosa, additional, Eythorsson, Elias, additional, Jonsson, Asbjorn, additional, Palsson, Runolfur, additional, Indridason, Olafur Skuli, additional, Aspelund, Thor, additional, Gislason, Gauti, additional, Olafsson, Andri, additional, Sverrisdottir, Ingigerdur Solveig, additional, Steingrimsdottir, Hlif, additional, Einarsson Long, Thorir, additional, Hultcrantz, Malin, additional, Landgren, Ola, additional, Harding, Stephen, additional, Durie, Brian G.M., additional, Love, Thorvardur Jon, additional, and Kristinsson, Sigurdur Y, additional

Published
2022
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7. Sars-Cov-2 Vaccinations Do Not Lead to Progression of Monoclonal Gammopathy of Undetermined Significance: Results from the Population-Based Istopmm Screening Study

Author

Palmason, Robert, primary, Eythorsson, Elias, additional, Rögnvaldsson, Sæmundur, additional, Thorsteinsdottir, Sigrun, additional, Ekberg, Sara, additional, Crowther, Michael, additional, Reed, Elin Ruth, additional, Oskarsson, Jon Þórir, additional, Sigurdardottir, Gudrun Asta, additional, Aspelund, Thor, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Sveinsdottir, Signy Vala, additional, Olafsson, Isleifur, additional, Thordardottir, Asdis Rosa, additional, Jonsson, Asbjorn, additional, Indridason, Olafur Skuli, additional, Gislason, Gauti, additional, Olafsson, Andri, additional, Sigurdsson, Jon Kristinn, additional, Steingrimsdottir, Hlif, additional, Einarsson Long, Thorir, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Harding, Stephen, additional, Landgren, Ola, additional, Palsson, Runolfur, additional, Love, Thorvardur Jon, additional, and Kristinsson, Sigurdur Y, additional

Published
2022
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8. Monoclonal Gammopathy of Undetermined Significance (MGUS) with Multiple Paraproteins: Results from the Population-Based Istopmm Screening Study

Author

Rögnvaldsson, Sæmundur, primary, Oskarsson, Jon Þórir, additional, Thorsteinsdottir, Sigrun, additional, Reed, Elin Ruth, additional, Sigurdardottir, Gudrun Asta, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Sigurdardottir, Margret, additional, Agnarsson, Bjarni Agnar, additional, Olafsson, Isleifur, additional, Thorsteinsdottir, Ingunn, additional, Sveinsdottir, Signy Vala, additional, Palmason, Robert, additional, Sigurdsson, Fridbjorn, additional, Thordardottir, Asdis Rosa, additional, Eythorsson, Elias, additional, Jonsson, Asbjorn, additional, Palsson, Runolfur, additional, Indridason, Olafur Skuli, additional, Aspelund, Thor, additional, Gislason, Gauti, additional, Olafsson, Andri, additional, Sigurdsson, Jon Kristinn, additional, Sverrisdottir, Ingigerdur S, additional, Hakonardottir, Gudlaug Katrin, additional, Einarsson Long, Thorir, additional, Danielsen, Ragnar, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Harding, Stephen, additional, Landgren, Ola, additional, Love, Thorvardur Jon, additional, and Kristinsson, Sigurdur Y, additional

Published
2022
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9. Screening for Monoclonal Gammopathy of Undetermined Significance: A Population-Based Randomized Clinical Trial. First Results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Author

Kristinsson, Sigurdur Y, primary, Rögnvaldsson, Sæmundur, additional, Thorsteinsdottir, Sigrun, additional, Reed, Elin Ruth, additional, Oskarsson, Jon Thorir Thorir, additional, Petursdottir, Iris, additional, Sigurdardottir, Gudrun Asta, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Sveinsdottir, Signy Vala, additional, Palmason, Robert, additional, Olafsson, Isleifur, additional, Sigurdsson, Fridbjorn, additional, Thordardottir, Asdis Rosa, additional, Eythorsson, Elias, additional, Jonsson, Asbjorn, additional, Palsson, Runolfur, additional, Indridason, Olafur Skuli, additional, Gislason, Gauti Kjartan, additional, Olafsson, Andri, additional, Sigurdsson, Jon Kristinn, additional, Sverrisdottir, Ingigerdur Solveig, additional, Juliusdottir, Maria Soffia, additional, Hakonardottir, Gudlaug Katrin, additional, Steingrimsdottir, Hlif, additional, Danielsen, Ragnar, additional, Kampanis, Petros, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Harding, Stephen, additional, Landgren, Ola, additional, and Love, Thorvardur Jon, additional

Published
2021
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10. Prevalence of Smoldering Multiple Myeloma: Results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Author

Thorsteinsdottir, Sigrun, primary, Gislason, Gauti Kjartan, additional, Aspelund, Thor, additional, Rögnvaldsson, Sæmundur, additional, Oskarsson, Jon Thorir Thorir, additional, Petursdottir, Iris, additional, Sigurdsson, Jon Kristinn, additional, Sigurdardottir, Gudrun Asta, additional, Thordardottir, Asdis Rosa, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Olafsson, Isleifur, additional, Eythorsson, Elias, additional, Jonsson, Asbjorn, additional, Kampanis, Petros, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Love, Thorvardur Jon, additional, Harding, Stephen, additional, Landgren, Ola, additional, and Kristinsson, Sigurdur Yngvi, additional

Published
2021
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11. Defining New Reference Intervals for Serum Free Light Chains in Individuals with Reduced Kidney Function: Results of the Population- Based on Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) Study

Author

Einarsson Long, Thorir, primary, Indridason, Olafur Skuli, additional, Palsson, Runolfur, additional, Rögnvaldsson, Sæmundur, additional, Love, Thorvardur Jon, additional, Thorsteinsdottir, Sigrun, additional, Sverrisdottir, Ingigerdur Solveig, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Olafsson, Isleifur, additional, Thordardottir, Asdis Rosa, additional, Eythorsson, Elias, additional, Jonsson, Asbjorn, additional, Gislason, Gauti, additional, Olafsson, Andri, additional, Steingrimsdottir, Hlif, additional, Kampanis, Petros, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Harding, Stephen, additional, Landgren, Ola, additional, and Kristinsson, Sigurdur Yngvi, additional

Published
2021
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12. Monitoring of Circulating Tumor Plasma Cells in Patients with Precursor Conditions of Multiple Myeloma: Data from the Prospective Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Author

Óskarsson, Jón Þórir, primary, Petursdottir, Iris, additional, Rögnvaldsson, Sæmundur, additional, Thorsteinsdottir, Sigrun, additional, Sigurdardottir, Gudrun Asta, additional, Thordardottir, Asdis Rosa, additional, Gislason, Gauti Kjartan, additional, Olafsson, Andri, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Palmason, Robert, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Olafsson, Isleifur, additional, Durie, Brian G.M., additional, Love, Thorvardur Jon, additional, and Kristinsson, Sigurdur Y, additional

Published
2021
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13. Estimating Selection Bias in Previous Monoclonal Gammopathy of Undetermined Significance Research - the Importance of Screening: Results from the Population-Based Screening Study Iceland Screens, Treats or Prevents Multiple Myeloma (iStopMM)

Author

Sigurbergsdóttir, Aðalbjörg Ýr, primary, Rögnvaldsson, Sæmundur, additional, Thorsteinsdottir, Sigrun, additional, Sverrisdottir, Ingigerdur Solveig, additional, Sigurdardottir, Gudrun Asta, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Olafsson, Isleifur, additional, Thordardottir, Asdis Rosa, additional, Gislason, Gauti Kjartan, additional, Olafsson, Andri, additional, Kampanis, Petros, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Harding, Stephen, additional, Landgren, Ola, additional, Love, Thorvardur Jon, additional, and Kristinsson, Sigurdur Y, additional

Published
2021
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14. Monoclonal Gammopathy of Undetermined Significance and COVID-19: Results from the Population-Based Iceland Screens Treats or Prevents Multiple Myeloma Study (iStopMM)

Author

Rögnvaldsson, Sæmundur, primary, Eythorsson, Elias, additional, Thorsteinsdottir, Sigrun, additional, Vidarsson, Brynjar, additional, Onundarson, Pall Torfi, additional, Agnarsson, Bjarni Agnar, additional, Sigurdardottir, Margret, additional, Thorsteinsdottir, Ingunn, additional, Olafsson, Isleifur, additional, Runolfsdottir, Hrafnhildur Linnet, additional, Helgason, Dadi, additional, Emilsdóttir, Arna, additional, Bjornsson, Aron H, additional, Kristjansdottir, Gudrun, additional, Thordardottir, Asdis Rosa, additional, Indridason, Olafur Skuli, additional, Jonsson, Asbjorn, additional, Gislason, Gauti Kjartan, additional, Olafsson, Andri, additional, Steingrimsdottir, Hlif, additional, Kampanis, Petros, additional, Hultcrantz, Malin, additional, Durie, Brian G.M., additional, Harding, Stephen, additional, Landgren, Ola, additional, Love, Thorvardur Jon, additional, Palsson, Runolfur, additional, and Kristinsson, Sigurdur Y, additional

Published
2021
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15. Predicting the Need for Upfront Bone Marrow Sampling in Individuals with MGUS: Derivation of a Multivariable Prediction Model Using the Prospective Population-Based Istopmm Cohort

Author

Eythorsson, Elias, Rögnvaldsson, Sæmundur, Thorsteinsdóttir, Sigrún, Reed, Elin Ruth, Sigurdardóttir, Gudrún Ásta, Vidarsson, Brynjar, Onundarson, Páll Torfi, Agnarsson, Bjarni, Sigurdardóttir, Margrét, Ólafsson, Ísleifur, Þorsteinsdóttir, Ingunn, Sveinsdottir, Signy Vala, Sigurdsson, Fridbjorn, Thórdardottir, Ásdis Rósa, Palsson, Runolfur, Indridason, Olafur, Einarsson Long, Thorir, Jonsson, Asbjorn, Gislason, Gauti Kjartan, Olafsson, Andri, Sigurdsson, Jon Kristinn, Steingrimsdottir, Hlif, Hultcrantz, Malin, Durie, Brian G.M., Harding, Stephen, Landgren, Ola, Aspelund, Thor, Love, Thorvardur Jon, and Kristinsson, Sigurdur Y

Published
2022
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16. Determining Hemodilution in Diagnostic Bone Marrow Samples in Multiple Myeloma and Its Precursors By Next-Generation Flow Cytometry: Data from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Author

Óskarsson, Jón Þórir, Rögnvaldsson, Sæmundur, Thorsteinsdóttir, Sigrún, þórðardóttir, Hrafnhildur Una, Hakonardottir, Gudlaug Katrin, Gunnarsson, Steinar Bragi, Sigurdardóttir, Gudrún Ásta, Thórdardottir, Ásdis Rósa, Gíslason, Gauti, Olafsson, Andri, Sigurdsson, Jon Kristinn, Vidarsson, Brynjar, Onundarson, Páll Torfi, Agnarsson, Bjarni Agnar, Palmason, Robert, Sigurdardóttir, Margrét, Thorsteinsdóttir, Ingunn, Ólafsson, Ísleifur, Flores-Montero, Juan, Orfao, Alberto, Durie, Brian G.M., Love, Thorvardur Jon, and Kristinsson, Sigurdur Y

Published
2022
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17. Monoclonal Gammopathy of Undetermined Significance and Risk of Chronic Kidney Disease: Results of the Population-Based Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Author

Einarsson Long, Thorir, Eythorsson, Elias, Rögnvaldsson, Sæmundur, Indridason, Olafur, Palsson, Runolfur, Thorsteinsdóttir, Sigrún, Sverrisdottir, Ingigerdur S, Aspelund, Thor, Vidarsson, Brynjar, Onundarson, Páll Torfi, Agnarsson, Bjarni, Sigurdardóttir, Margrét, Thorsteinsdottir, Ingunn, Ólafsson, Ísleifur, Thordardottir, Asdis Rosa, Jonsson, Asbjorn, Gislason, Gauti Kjartan, Olafsson, Andri, Steingrimsdottir, Hlif, Hultcrantz, Malin, Durie, Brian G.M., Harding, Stephen, Landgren, Ola, Love, Thorvardur Jon, and Kristinsson, Sigurdur Y

Published
2022
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18. Hypercalcemia in Individuals with Monoclonal Gammopathy of Undetermined Significance: Results from the Istopmm Study

Author

Jónsdóttir, Ástrún Helga, Rögnvaldsson, Sæmundur, Sigurjónsdóttir, Helga Ágústa, Thorsteinsdóttir, Sigrún, Vidarsson, Brynjar, Onundarson, Páll Torfi, Agnarsson, Bjarni, Sigurdardóttir, Margrét, Thorsteinsdóttir, Ingunn, Ólafsson, Ísleifur, Sveinsdottir, Signy Vala, Palmason, Robert, Thórdardottir, Ásdis Rósa, Eythorsson, Elias, Jonsson, Asbjorn, Palsson, Runolfur, Indridason, Olafur Skuli, Gislason, Gauti Kjartan, Olafsson, Andri, Sigurdsson, Jon Kristinn, Sverrisdottir, Ingigerdur S, Einarsson Long, Thorir, Aspelund, Thor, Hultcrantz, Malin, Durie, Brian G.M., Harding, Stephen, Landgren, Ola, Love, Thorvardur Jon, and Kristinsson, Sigurdur Y

Published
2022
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19. Circulating Tumor Plasma Cells in the Screened Istopmm Smoldering Multiple Myeloma Cohort

Author

Thorsteinsdóttir, Sigrún, Oskarsson, Jon Þórir, Rögnvaldsson, Sæmundur, Gíslason, Gauti, Aspelund, Thor, Sigurdardóttir, Gudrún Ásta, Thórdardottir, Ásdis Rósa, Vidarsson, Brynjar, Onundarson, Páll Torfi, Agnarsson, Bjarni Agnar, Sigurdardóttir, Margrét, Thorsteinsdóttir, Ingunn, Ólafsson, Ísleifur, Eythorsson, Elias, Jónsson, Ásbjorn, Hultcrantz, Malin, Landgren, Ola, Harding, Stephen, Durie, Brian G.M., Love, Thorvardur Jon, and Kristinsson, Sigurdur Y

Published
2022
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20. A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma

Author

Smith, Dirk, Helgason, Hannes, Sulem, Patrick, Bjornsdottir, Unnur Steina, Lim, Ai Ching, Sveinbjornsson, Gardar, Hasegawa, Haruki, Brown, Michael, Ketchem, Randal R, Gavala, Monica, Garrett, Logan, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Magnusson, Olafur T, Eyjolfsson, Gudmundur I, Olafsson, Isleifur, Onundarson, Pall Torfi, Sigurdardottir, Olof, Gislason, David, Gislason, Thorarinn, Ludviksson, Bjorn Runar, Ludviksdottir, Dora, Boezen, H Marike, Heinzmann, Andrea, Krueger, Marcus, Porsbjerg, Celeste, Ahluwalia, Tarunveer S, Waage, Johannes, Backer, Vibeke, Deichmann, Klaus A, Koppelman, Gerard H, Bønnelykke, Klaus, Bisgaard, Hans, Masson, Gisli, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F, Johnston, James A, Jonsdottir, Ingileif, Stefansson, Kari, Smith, Dirk, Helgason, Hannes, Sulem, Patrick, Bjornsdottir, Unnur Steina, Lim, Ai Ching, Sveinbjornsson, Gardar, Hasegawa, Haruki, Brown, Michael, Ketchem, Randal R, Gavala, Monica, Garrett, Logan, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Magnusson, Olafur T, Eyjolfsson, Gudmundur I, Olafsson, Isleifur, Onundarson, Pall Torfi, Sigurdardottir, Olof, Gislason, David, Gislason, Thorarinn, Ludviksson, Bjorn Runar, Ludviksdottir, Dora, Boezen, H Marike, Heinzmann, Andrea, Krueger, Marcus, Porsbjerg, Celeste, Ahluwalia, Tarunveer S, Waage, Johannes, Backer, Vibeke, Deichmann, Klaus A, Koppelman, Gerard H, Bønnelykke, Klaus, Bisgaard, Hans, Masson, Gisli, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F, Johnston, James A, Jonsdottir, Ingileif, and Stefansson, Kari

Abstract

IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (β = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.

Published
2017

21. A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma

Author

Smith, Dirk, primary, Helgason, Hannes, additional, Sulem, Patrick, additional, Bjornsdottir, Unnur Steina, additional, Lim, Ai Ching, additional, Sveinbjornsson, Gardar, additional, Hasegawa, Haruki, additional, Brown, Michael, additional, Ketchem, Randal R., additional, Gavala, Monica, additional, Garrett, Logan, additional, Jonasdottir, Adalbjorg, additional, Jonasdottir, Aslaug, additional, Sigurdsson, Asgeir, additional, Magnusson, Olafur T., additional, Eyjolfsson, Gudmundur I., additional, Olafsson, Isleifur, additional, Onundarson, Pall Torfi, additional, Sigurdardottir, Olof, additional, Gislason, David, additional, Gislason, Thorarinn, additional, Ludviksson, Bjorn Runar, additional, Ludviksdottir, Dora, additional, Boezen, H. Marike, additional, Heinzmann, Andrea, additional, Krueger, Marcus, additional, Porsbjerg, Celeste, additional, Ahluwalia, Tarunveer S., additional, Waage, Johannes, additional, Backer, Vibeke, additional, Deichmann, Klaus A., additional, Koppelman, Gerard H., additional, Bønnelykke, Klaus, additional, Bisgaard, Hans, additional, Masson, Gisli, additional, Thorsteinsdottir, Unnur, additional, Gudbjartsson, Daniel F., additional, Johnston, James A., additional, Jonsdottir, Ingileif, additional, and Stefansson, Kari, additional

Published
2017
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24. Prior cancer and risk of monoclonal gammopathy of undetermined significance: a population-based study in Iceland and Sweden.

Author

Rögnvaldsson S, Thorsteinsdóttir S, Syriopoulou E, Sverrisdottir I, Turesson I, Eythorsson E, Oskarsson JT, Long TE, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Olafsson I, Thorsteinsdottir I, Aspelund T, Gislason GK, Olafsson A, Sigurdsson JK, Hultcrantz M, Durie BGM, Harding S, Bjorkholm M, Landgren O, Love TJ, and Kristinsson SY

Subjects
Humans, Iceland epidemiology, Sweden epidemiology, Male, Female, Middle Aged, Aged, Risk Factors, Multiple Myeloma epidemiology, Multiple Myeloma diagnosis, Multiple Myeloma etiology, Neoplasms epidemiology, Neoplasms etiology, Neoplasms diagnosis, Disease Progression, Adult, Population Surveillance, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance diagnosis
Abstract

There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with a higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore constitute a target population for MGUS screening. This two-part study is the first study to evaluate a relationship between MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio=1.10; 95% confidence interval: 1.00-1.20). This excess risk was limited to prior cancers in the year preceding MGUS screening. A history of prior cancer was associated with progression of MGUS, except for myeloid malignancies which were associated with a lower risk of progression (hazard ratio=0.37; 95% confidence interval: 0.16-0.89; P=0.028). Our findings indicate that a prior cancer is not a significant etiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a prior cancer.

Published
2024
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