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Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome

The typical anti-phospholipid antibodies (APLA) in the anti-phospholipid syndrome (APS) are reactive with the phospholipid-binding protein β2GPI as well as a growing list of other protein targets. The relation of APLA to natural antibodies and the fuzzy set of autoantigens involved provoked us to st...

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Autores principales: Pashova, Shina, Balabanski, Lubomir, Elmadjian, Gabriel, Savov, Alexey, Stoyanova, Elena, Shivarov, Velizar, Petrov, Peter, Pashov, Anastas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043687/
https://www.ncbi.nlm.nih.gov/pubmed/35493489
http://dx.doi.org/10.3389/fimmu.2022.865232
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author Pashova, Shina
Balabanski, Lubomir
Elmadjian, Gabriel
Savov, Alexey
Stoyanova, Elena
Shivarov, Velizar
Petrov, Peter
Pashov, Anastas
author_facet Pashova, Shina
Balabanski, Lubomir
Elmadjian, Gabriel
Savov, Alexey
Stoyanova, Elena
Shivarov, Velizar
Petrov, Peter
Pashov, Anastas
author_sort Pashova, Shina
collection PubMed
description The typical anti-phospholipid antibodies (APLA) in the anti-phospholipid syndrome (APS) are reactive with the phospholipid-binding protein β2GPI as well as a growing list of other protein targets. The relation of APLA to natural antibodies and the fuzzy set of autoantigens involved provoked us to study the changes in the IgM repertoire in APS. To this end, peptides selected by serum IgM from a 7-residue linear peptide phage display library (PDL) were deep sequenced. The analysis was aided by a novel formal representation of the Igome (the mimotope set reflecting the IgM specificities) in the form of a sequence graph. The study involved women with APLA and habitual abortions (n=24) compared to age-matched clinically healthy pregnant women (n=20). Their pooled Igomes (297 028 mimotope sequences) were compared also to the global public repertoire Igome of pooled donor plasma IgM (n=2 796 484) and a set of 7-mer sequences found in the J regions of human immunoglobulins (n=4 433 252). The pooled Igome was represented as a graph connecting the sequences as similar as the mimotopes of the same monoclonal antibody. The criterion was based on previously published data. In the resulting graph, identifiable clusters of vertices were considered related to the footprints of overlapping antibody cross-reactivities. A subgraph based on the clusters with a significant differential expression of APS patients’ mimotopes contained predominantly specificities underrepresented in APS. The differentially expressed IgM footprints showed also an increased cross-reactivity with immunoglobulin J regions. The specificities underexpressed in APS had a higher correlation with public specificities than those overexpressed. The APS associated specificities were strongly related also to the human peptidome with 1 072 mimotope sequences found in 7 519 human proteins. These regions were characterized by low complexity. Thus, the IgM repertoire of the APS patients was found to be characterized by a significant reduction of certain public specificities found in the healthy controls with targets representing low complexity linear self-epitopes homologous to human antibody J regions.
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spelling pubmed-90436872022-04-28 Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome Pashova, Shina Balabanski, Lubomir Elmadjian, Gabriel Savov, Alexey Stoyanova, Elena Shivarov, Velizar Petrov, Peter Pashov, Anastas Front Immunol Immunology The typical anti-phospholipid antibodies (APLA) in the anti-phospholipid syndrome (APS) are reactive with the phospholipid-binding protein β2GPI as well as a growing list of other protein targets. The relation of APLA to natural antibodies and the fuzzy set of autoantigens involved provoked us to study the changes in the IgM repertoire in APS. To this end, peptides selected by serum IgM from a 7-residue linear peptide phage display library (PDL) were deep sequenced. The analysis was aided by a novel formal representation of the Igome (the mimotope set reflecting the IgM specificities) in the form of a sequence graph. The study involved women with APLA and habitual abortions (n=24) compared to age-matched clinically healthy pregnant women (n=20). Their pooled Igomes (297 028 mimotope sequences) were compared also to the global public repertoire Igome of pooled donor plasma IgM (n=2 796 484) and a set of 7-mer sequences found in the J regions of human immunoglobulins (n=4 433 252). The pooled Igome was represented as a graph connecting the sequences as similar as the mimotopes of the same monoclonal antibody. The criterion was based on previously published data. In the resulting graph, identifiable clusters of vertices were considered related to the footprints of overlapping antibody cross-reactivities. A subgraph based on the clusters with a significant differential expression of APS patients’ mimotopes contained predominantly specificities underrepresented in APS. The differentially expressed IgM footprints showed also an increased cross-reactivity with immunoglobulin J regions. The specificities underexpressed in APS had a higher correlation with public specificities than those overexpressed. The APS associated specificities were strongly related also to the human peptidome with 1 072 mimotope sequences found in 7 519 human proteins. These regions were characterized by low complexity. Thus, the IgM repertoire of the APS patients was found to be characterized by a significant reduction of certain public specificities found in the healthy controls with targets representing low complexity linear self-epitopes homologous to human antibody J regions. Frontiers Media S.A. 2022-04-13 /pmc/articles/PMC9043687/ /pubmed/35493489 http://dx.doi.org/10.3389/fimmu.2022.865232 Text en Copyright © 2022 Pashova, Balabanski, Elmadjian, Savov, Stoyanova, Shivarov, Petrov and Pashov https://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
Pashova, Shina
Balabanski, Lubomir
Elmadjian, Gabriel
Savov, Alexey
Stoyanova, Elena
Shivarov, Velizar
Petrov, Peter
Pashov, Anastas
Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome
title Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome
title_full Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome
title_fullStr Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome
title_full_unstemmed Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome
title_short Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome
title_sort restriction of the global igm repertoire in antiphospholipid syndrome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043687/
https://www.ncbi.nlm.nih.gov/pubmed/35493489
http://dx.doi.org/10.3389/fimmu.2022.865232
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