BACKGROUND: IgE antibody-producing B cells are enriched in the nasal mucosa in patients with allergic rhinitis because of local class switching to IgE. The expressed IgE VH genes also undergo somatic hypermutation in situ to generate clonal families. The antigenic driving force behind these events is unknown. OBJECTIVE: To examine the possible involvement of a superantigen in allergic rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from allergic patients and the IgA VH use in the same biopsy specimens and also those from nonallergic controls. METHODS: We extracted mRNA from the nasal biopsy specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7 allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA sequences were compared with those of control subjects. We constructed a molecular model of VH5 to locate amino acids of interest. RESULTS: We observed a significantly increased frequency of IgE and IgA VH5 transcripts in the nasal mucosa of the allergic patients compared with the normal PBMC repertoire. Within IgE and IgA VH5 sequences in the nasal mucosa, the distribution of replacement amino acids was skewed toward the immunoglobulin framework regions. Three of 4 nonintrinsic hotspots of mutation identified in the VH5 sequences were in framework region 1. The hotspots and a conserved VH5-specific framework residue form a tight cluster on the surface of VH5. CONCLUSION: Our results provide evidence for the activity of a superantigen in the nasal mucosa in patients with allergic rhinitis.
BACKGROUND: IgE antibody-producing B cells are enriched in the nasal mucosa in patients with allergic rhinitis because of local class switching to IgE. The expressed IgE VH genes also undergo somatic hypermutation in situ to generate clonal families. The antigenic driving force behind these events is unknown. OBJECTIVE: To examine the possible involvement of a superantigen in allergic rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from allergic patients and the IgA VH use in the same biopsy specimens and also those from nonallergic controls. METHODS: We extracted mRNA from the nasal biopsy specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7 allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA sequences were compared with those of control subjects. We constructed a molecular model of VH5 to locate amino acids of interest. RESULTS: We observed a significantly increased frequency of IgE and IgA VH5 transcripts in the nasal mucosa of the allergic patients compared with the normal PBMC repertoire. Within IgE and IgA VH5 sequences in the nasal mucosa, the distribution of replacement amino acids was skewed toward the immunoglobulin framework regions. Three of 4 nonintrinsic hotspots of mutation identified in the VH5 sequences were in framework region 1. The hotspots and a conserved VH5-specific framework residue form a tight cluster on the surface of VH5. CONCLUSION: Our results provide evidence for the activity of a superantigen in the nasal mucosa in patients with allergic rhinitis.
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
Authors: Tobias Rogosch; Sebastian Kerzel; Kam Hon Hoi; Zhixin Zhang; Rolf F Maier; Gregory C Ippolito; Michael Zemlin Journal: Front Immunol Date: 2012-06-28 Impact factor: 7.561
Authors: Louise Saul; Kristina M Ilieva; Heather J Bax; Panagiotis Karagiannis; Isabel Correa; Irene Rodriguez-Hernandez; Debra H Josephs; Isabella Tosi; Isioma U Egbuniwe; Sara Lombardi; Silvia Crescioli; Carl Hobbs; Federica Villanova; Anthony Cheung; Jenny L C Geh; Ciaran Healy; Mark Harries; Victoria Sanz-Moreno; David J Fear; James F Spicer; Katie E Lacy; Frank O Nestle; Sophia N Karagiannis Journal: Sci Rep Date: 2016-07-14 Impact factor: 4.379
Authors: Yu-Chang B Wu; Louisa K James; Jason A Vander Heiden; Mohamed Uduman; Stephen R Durham; Steven H Kleinstein; David Kipling; Hannah J Gould Journal: J Allergy Clin Immunol Date: 2014-09 Impact factor: 10.793