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- W2939977802 abstract "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." @default.
- W2939977802 created "2019-04-25" @default.
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- W2939977802 date "2017-09-01" @default.
- W2939977802 modified "2023-09-24" @default.
- W2939977802 title "2504" @default.
- W2939977802 doi "https://doi.org/10.1017/cts.2017.51" @default.
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