In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-4-13)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.865232
DOI:
10.3389/fimmu.2022.865232.s001
DOI:
10.3389/fimmu.2022.865232.s002
DOI:
10.3389/fimmu.2022.865232.s003
DOI:
10.3389/fimmu.2022.865232.s004
DOI:
10.3389/fimmu.2022.865232.s005
DOI:
10.3389/fimmu.2022.865232.s006
DOI:
10.3389/fimmu.2022.865232.s007
DOI:
10.3389/fimmu.2022.865232.s008
DOI:
10.3389/fimmu.2022.865232.s009
DOI:
10.3389/fimmu.2022.865232.s010
DOI:
10.3389/fimmu.2022.865232.s011
DOI:
10.3389/fimmu.2022.865232.s012
DOI:
10.3389/fimmu.2022.865232.s013
DOI:
10.3389/fimmu.2022.865232.s014
DOI:
10.3389/fimmu.2022.865232.s015
DOI:
10.3389/fimmu.2022.865232.s016
DOI:
10.3389/fimmu.2022.865232.s017
DOI:
10.3389/fimmu.2022.865232.s018
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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