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OBJECTIVES/SPECIFIC AIMS: Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies to the keratinocyte adhesion protein desmoglein 3. Several other autoimmune diseases have defective B cell tolerance checkpoints, resulting in the accumulation of self-reactive and po...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2017-09-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866117000516/type/journal_article |
| _version_ | 1811156821440724992 |
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| author | Nina Ran Christoph Ellebrecht Eun Jung Choi Aimee Payne |
| author_facet | Nina Ran Christoph Ellebrecht Eun Jung Choi Aimee Payne |
| author_sort | Nina Ran |
| collection | DOAJ |
| description | OBJECTIVES/SPECIFIC AIMS: Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies to the keratinocyte adhesion protein desmoglein 3. Several other autoimmune diseases have defective B cell tolerance checkpoints, resulting in the accumulation of self-reactive and polyreactive B cells. METHODS/STUDY POPULATION: The present work aims to determine whether PV patients develop normal tolerance to self-antigens other than desmoglein 3, as a potential “first hit” in the development of autoimmunity. We use FACS to isolate single B cells at 4 developmental stages from 8 PV patients. We perform single-cell RT-PCR to amplify each B cell receptor, produce monoclonal antibodies, and screen these for autoreactivity using ELISA/IF to several self-antigens. At each B cell stage, we compare the frequencies of self-reactive and polyreactive B cells to those found in healthy controls. RESULTS/ANTICIPATED RESULTS: We anticipate similar frequencies between PV patients and controls, suggesting that the B cell repertoire in PV patients develops normally at early checkpoints. DISCUSSION/SIGNIFICANCE OF IMPACT: The absence of generalized reactivity would distinguish PV from other autoimmune diseases and would show that PV arises from a specific break in tolerance to a single self-antigen (desmoglein 3) during late B cell maturation. Such a result would further support PV as an ideal candidate for targeted immunotherapy. |
| first_indexed | 2024-04-10T04:57:30Z |
| format | Article |
| id | doaj.art-e8244dca516648a09295be6468705ec2 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-10T04:57:30Z |
| publishDate | 2017-09-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-e8244dca516648a09295be6468705ec22023-03-09T12:30:06ZengCambridge University PressJournal of Clinical and Translational Science2059-86612017-09-011101010.1017/cts.2017.512504Nina Ran0Christoph Ellebrecht1Eun Jung Choi2Aimee Payne3School of Medicine, University of Pennsylvania, Philadelphia, PA, USASchool of Medicine, University of Pennsylvania, Philadelphia, PA, USASchool of Medicine, University of Pennsylvania, Philadelphia, PA, USASchool of Medicine, University of Pennsylvania, Philadelphia, PA, USAOBJECTIVES/SPECIFIC AIMS: Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies to the keratinocyte adhesion protein desmoglein 3. Several other autoimmune diseases have defective B cell tolerance checkpoints, resulting in the accumulation of self-reactive and polyreactive B cells. METHODS/STUDY POPULATION: The present work aims to determine whether PV patients develop normal tolerance to self-antigens other than desmoglein 3, as a potential “first hit” in the development of autoimmunity. We use FACS to isolate single B cells at 4 developmental stages from 8 PV patients. We perform single-cell RT-PCR to amplify each B cell receptor, produce monoclonal antibodies, and screen these for autoreactivity using ELISA/IF to several self-antigens. At each B cell stage, we compare the frequencies of self-reactive and polyreactive B cells to those found in healthy controls. RESULTS/ANTICIPATED RESULTS: We anticipate similar frequencies between PV patients and controls, suggesting that the B cell repertoire in PV patients develops normally at early checkpoints. DISCUSSION/SIGNIFICANCE OF IMPACT: The absence of generalized reactivity would distinguish PV from other autoimmune diseases and would show that PV arises from a specific break in tolerance to a single self-antigen (desmoglein 3) during late B cell maturation. Such a result would further support PV as an ideal candidate for targeted immunotherapy.https://www.cambridge.org/core/product/identifier/S2059866117000516/type/journal_article |
| spellingShingle | Nina Ran Christoph Ellebrecht Eun Jung Choi Aimee Payne 2504 Journal of Clinical and Translational Science |
| title | 2504 |
| title_full | 2504 |
| title_fullStr | 2504 |
| title_full_unstemmed | 2504 |
| title_short | 2504 |
| title_sort | 2504 |
| url | https://www.cambridge.org/core/product/identifier/S2059866117000516/type/journal_article |
| work_keys_str_mv | AT ninaran 2504 AT christophellebrecht 2504 AT eunjungchoi 2504 AT aimeepayne 2504 |