Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis.
BACKGROUND
Eosinophilic oesophagitis (EO) is an emerging yet increasingly prevalent disorder characterised by a dense and selective eosinophilic infiltration of the oesophageal wall. While EO is considered an atopic disease primarily triggered by food antigens, disparities between standard allergen testing and clinical responses to exclusion diets suggest the participation of distinct antigen-specific immunoglobulin E (IgE) in the pathophysiology of EO.


OBJECTIVE
To find evidence for a local IgE response.


METHODS
Endoscopic biopsies of the distal oesophagus of atopic and non-atopic EO and control individuals (CTL) were processed for immunohistochemistry and immunofluorescence to assess the presence of B cells, mast cells, and IgE-bearing cells. Oesophageal RNA was analysed for the expression of genes involved in B cell activation, class switch recombination to IgE and IgE production, including germline transcripts (GLTs), activation-induced cytidine deaminase (AID), IgE heavy chain (Cepsilon) and mature IgE mRNA using polymerase chain reaction and microarray analysis.


RESULTS
Regardless of atopy, EO showed increased density of B cells (p<0.05) and of IgE-bounded mast cells compared to CTL. Both EO and CTL expressed muGLT, epsilonGLT, gamma4GLT, AID, Cepsilon and IgE mRNA. However, the frequency of expression of total GLTs (p = 0.002), epsilonGLT (p = 0.024), and Cepsilon (p = 0.0003) was significantly higher in EO than in CTL, independent of the atopic status.


CONCLUSIONS
These results support the heretofore unproven occurrence of both local immunoglobulin class switching to IgE and IgE production in the oesophageal mucosa of EO patients. Sensitisation and activation of mast cells involving local IgE may therefore critically contribute to disease pathogenesis.
Vicario
M
M
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Blanchard
C
C
Stringer
K F
KF
Collins
M H
MH
Mingler
M K
MK
Ahrens
A
A
Putnam
P E
PE
Abonia
J P
JP
Santos
J
J
Rothenberg
M E
ME
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D004802:Eosinophilia / Q000276:immunology*; D004941:Esophagitis / Q000276:immunology*; D004947:Esophagus / Q000276:immunology; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D014158:Transcription, Genetic
D018793:Interleukin-13; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E