BACKGROUND: It is generally assumed that all immunoglobulin isotopes develop under antigen selection pressure, leading to dramatic increases in antigen-binding affinity. As activated B cells proliferate, somatic mutations accumulate in the regions of the immunoglobulin gene associated with antigen binding. Emerging evidence from studies investigating mutations in variable region sequences of IgE antibodies suggest that IgE may develop under less selection pressure than other isotypes. Recent studies have focused on IgE mutation patterns in sequences from the blood of allergic individuals. There is, however, little evidence of these patterns in IgE sequences isolated from tissue. METHODS: Semi-nested reverse-transcription polymerase chain reaction was used to amplify the V region of IgE sequences from nasal tissue of individuals with chronic rhinosinusitis with nasal polyps (CRSwNPs). IgE sequences were analyzed for evidence of antigen selection and compared with previously reported IgE sequences from other inflammatory and allergic disorders and nonallergic individuals. RESULTS: IgE sequences were successfully amplified from four individuals with CRSwNPs. Of 217 sequences amplified, 38 were unique, 31 of which were from tissue. Identification of the IGHV, IGHD, and IGHJ genes making up each sequence showed overrepresentation of an unusual gene in one individual, but otherwise normal gene usage. Mutation analysis revealed that only 5 of the 31 unique sequences from tissue show clear evidence of antigen selection. CONCLUSION: With little influence from antigen selection, IgE antibodies are unlikely to be highly specific for antigens. Consequently, these findings have significant implications for the relevance of specific IgE, e.g., Staphylococcus aureus enterotoxin or fungal-specific IgE, in CRSwNP pathogenesis. Whether specific IgE expression is tightly related to pathogenesis or is merely a byproduct of B-cell interactions in local mucosa with colonizing organisms remains unresolved.
BACKGROUND: It is generally assumed that all immunoglobulin isotopes develop under antigen selection pressure, leading to dramatic increases in antigen-binding affinity. As activated B cells proliferate, somatic mutations accumulate in the regions of the immunoglobulin gene associated with antigen binding. Emerging evidence from studies investigating mutations in variable region sequences of IgE antibodies suggest that IgE may develop under less selection pressure than other isotypes. Recent studies have focused on IgE mutation patterns in sequences from the blood of allergic individuals. There is, however, little evidence of these patterns in IgE sequences isolated from tissue. METHODS: Semi-nested reverse-transcription polymerase chain reaction was used to amplify the V region of IgE sequences from nasal tissue of individuals with chronic rhinosinusitis with nasal polyps (CRSwNPs). IgE sequences were analyzed for evidence of antigen selection and compared with previously reported IgE sequences from other inflammatory and allergic disorders and nonallergic individuals. RESULTS: IgE sequences were successfully amplified from four individuals with CRSwNPs. Of 217 sequences amplified, 38 were unique, 31 of which were from tissue. Identification of the IGHV, IGHD, and IGHJ genes making up each sequence showed overrepresentation of an unusual gene in one individual, but otherwise normal gene usage. Mutation analysis revealed that only 5 of the 31 unique sequences from tissue show clear evidence of antigen selection. CONCLUSION: With little influence from antigen selection, IgE antibodies are unlikely to be highly specific for antigens. Consequently, these findings have significant implications for the relevance of specific IgE, e.g., Staphylococcus aureus enterotoxin or fungal-specific IgE, in CRSwNP pathogenesis. Whether specific IgE expression is tightly related to pathogenesis or is merely a byproduct of B-cell interactions in local mucosa with colonizing organisms remains unresolved.
Authors: Mattias Levin; Jasmine J King; Jacob Glanville; Katherine J L Jackson; Timothy J Looney; Ramona A Hoh; Adriano Mari; Morgan Andersson; Lennart Greiff; Andrew Z Fire; Scott D Boyd; Mats Ohlin Journal: J Allergy Clin Immunol Date: 2015-11-11 Impact factor: 10.793