Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years
Pemphigus vulgaris (PV) is a prototypic tissue-specific autoantibody-mediated disease in which anti-desmoglein 3 (Dsg3) immunoglobulin G (IgG) autoantibodies cause life-threatening blistering. We characterized the autoimmune B-cell response over 14 patient-years in two patients with active and relap...
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2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294994/ |
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pubmed-42949942015-09-01 Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years Hammers, Christoph M. Chen, Jing Lin, Chenyan Kacir, Stephen Siegel, Don L. Payne, Aimee S. Stanley, John R. Article Pemphigus vulgaris (PV) is a prototypic tissue-specific autoantibody-mediated disease in which anti-desmoglein 3 (Dsg3) immunoglobulin G (IgG) autoantibodies cause life-threatening blistering. We characterized the autoimmune B-cell response over 14 patient-years in two patients with active and relapsing disease, then in one of these patients after long-term remission induced by multiple courses of rituximab (anti-CD20 antibody). Characterization of the anti-Dsg3 IgG+ repertoire by antibody phage display (APD) and PCR indicated that 6 clonal lines persisted in patient 1 (PV3) over 5.5 years, with only one new clone detected. Six clonal lines persisted in patient 2 (PV1) for 4 years, of which 5 persisted for another 4.5 years without any new clones detected. However, after long-term clinical and serologic remission, ~11 years after initial characterization, we could no longer detect any anti-Dsg3 clones in PV1 by APD. Similarly, in another PV patient, ~4.5 years after a course of rituximab that induced long-term remission, anti-Dsg3 B-cell clones were undetectable. These data suggest that in PV a given set of non-tolerant B-cell lineages causes autoimmune disease and that new sets do not frequently or continually escape tolerance. Therapy such as rituximab, aimed at eliminating these aberrant sets of lineages, may be effective for disease because new ones are unlikely to develop. 2014-07-14 2015-03 /pmc/articles/PMC4294994/ /pubmed/25142730 http://dx.doi.org/10.1038/jid.2014.291 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Hammers, Christoph M. Chen, Jing Lin, Chenyan Kacir, Stephen Siegel, Don L. Payne, Aimee S. Stanley, John R. |
| spellingShingle |
Hammers, Christoph M. Chen, Jing Lin, Chenyan Kacir, Stephen Siegel, Don L. Payne, Aimee S. Stanley, John R. Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years |
| author_facet |
Hammers, Christoph M. Chen, Jing Lin, Chenyan Kacir, Stephen Siegel, Don L. Payne, Aimee S. Stanley, John R. |
| author_sort |
Hammers, Christoph M. |
| title |
Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years |
| title_short |
Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years |
| title_full |
Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years |
| title_fullStr |
Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years |
| title_full_unstemmed |
Persistence of Anti-Desmoglein 3 IgG+ B-Cell Clones in Pemphigus Patients Over Years |
| title_sort |
persistence of anti-desmoglein 3 igg+ b-cell clones in pemphigus patients over years |
| description |
Pemphigus vulgaris (PV) is a prototypic tissue-specific autoantibody-mediated disease in which anti-desmoglein 3 (Dsg3) immunoglobulin G (IgG) autoantibodies cause life-threatening blistering. We characterized the autoimmune B-cell response over 14 patient-years in two patients with active and relapsing disease, then in one of these patients after long-term remission induced by multiple courses of rituximab (anti-CD20 antibody). Characterization of the anti-Dsg3 IgG+ repertoire by antibody phage display (APD) and PCR indicated that 6 clonal lines persisted in patient 1 (PV3) over 5.5 years, with only one new clone detected. Six clonal lines persisted in patient 2 (PV1) for 4 years, of which 5 persisted for another 4.5 years without any new clones detected. However, after long-term clinical and serologic remission, ~11 years after initial characterization, we could no longer detect any anti-Dsg3 clones in PV1 by APD. Similarly, in another PV patient, ~4.5 years after a course of rituximab that induced long-term remission, anti-Dsg3 B-cell clones were undetectable. These data suggest that in PV a given set of non-tolerant B-cell lineages causes autoimmune disease and that new sets do not frequently or continually escape tolerance. Therapy such as rituximab, aimed at eliminating these aberrant sets of lineages, may be effective for disease because new ones are unlikely to develop. |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294994/ |
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1613176818179768320 |