AI Article Synopsis
- - Pemphigus vulgaris (PV) is a serious blistering disease driven by autoantibodies targeting desmoglein 3 (Dsg3), with researchers cloning anti-Dsg3 antibodies from four patients to analyze their characteristics.
- - The study identified that the pathogenic autoantibodies from all patients were of the VH1-46 type, which surprisingly had few mutations compared to expected.
- - Findings show that VH1-46 autoantibodies can still bind to Dsg3 even without many mutations, suggesting these types of antibodies may be more prevalent in PV due to their efficient autoreactivity and common immune response across different patients.
Article Abstract
Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies (autoAbs) against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3 antibodies (Abs) from four PV patients and identify pathogenic VH1-46 autoAbs from all four patients. Unexpectedly, VH1-46 autoAbs had relatively few replacement mutations. We reverted antibody somatic mutations to their germline sequences to determine the requirement of mutations for autoreactivity. Three of five VH1-46 germline-reverted Abs maintain Dsg3 binding, compared with zero of five non-VH1-46 germline-reverted Abs. Site-directed mutagenesis of VH1-46 Abs demonstrates that acidic amino-acid residues introduced by somatic mutation or heavy chain VDJ recombination are necessary and sufficient for Dsg3 binding. Our data suggest that VH1-46 autoantibody gene usage is commonly found in PV because VH1-46 Abs require few to no mutations to acquire Dsg3 autoreactivity, which may favour their early selection. Common VH gene usage indicates common humoral immune responses, even among unrelated patients.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120239 | PMC |
| http://dx.doi.org/10.1038/ncomms5167 | DOI Listing |
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