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Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome

The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has b...

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Autores principales: Pathak, Shelly, Rowczenio, Dorota, Lara-Reyna, Samuel, Kacar, Mark, Owen, Roger, Doody, Gina, Krause, Karoline, Lachmann, Helen, Doffinger, Rainer, Newton, Darren, Savic, Sinisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793813/
https://www.ncbi.nlm.nih.gov/pubmed/33424831
http://dx.doi.org/10.3389/fimmu.2020.569006
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author Pathak, Shelly
Rowczenio, Dorota
Lara-Reyna, Samuel
Kacar, Mark
Owen, Roger
Doody, Gina
Krause, Karoline
Lachmann, Helen
Doffinger, Rainer
Newton, Darren
Savic, Sinisa
author_facet Pathak, Shelly
Rowczenio, Dorota
Lara-Reyna, Samuel
Kacar, Mark
Owen, Roger
Doody, Gina
Krause, Karoline
Lachmann, Helen
Doffinger, Rainer
Newton, Darren
Savic, Sinisa
author_sort Pathak, Shelly
collection PubMed
description The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder.
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spelling pubmed-77938132021-01-09 Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome Pathak, Shelly Rowczenio, Dorota Lara-Reyna, Samuel Kacar, Mark Owen, Roger Doody, Gina Krause, Karoline Lachmann, Helen Doffinger, Rainer Newton, Darren Savic, Sinisa Front Immunol Immunology The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC7793813/ /pubmed/33424831 http://dx.doi.org/10.3389/fimmu.2020.569006 Text en Copyright © 2020 Pathak, Rowczenio, Lara-Reyna, Kacar, Owen, Doody, Krause, Lachmann, Doffinger, Newton and Savic http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pathak, Shelly
Rowczenio, Dorota
Lara-Reyna, Samuel
Kacar, Mark
Owen, Roger
Doody, Gina
Krause, Karoline
Lachmann, Helen
Doffinger, Rainer
Newton, Darren
Savic, Sinisa
Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome
title Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome
title_full Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome
title_fullStr Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome
title_full_unstemmed Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome
title_short Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome
title_sort evidence of b cell clonality and investigation into properties of the igm in patients with schnitzler syndrome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793813/
https://www.ncbi.nlm.nih.gov/pubmed/33424831
http://dx.doi.org/10.3389/fimmu.2020.569006
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