Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression.
Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-beta-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phl p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF-beta expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phl p 5-specific IgA2 Abs increased after a 2-year treatment (approximately 8-fold increase, p = 0.002) in contrast to IgA1. Increases in polymeric Abs to Phl p 5 (approximately 2-fold increase, p = 0.02) and in nasal TGF-beta mRNA (p = 0.05) were also observed, and TGF-beta mRNA correlated with serum Phl p 5 IgA2 (r = 0.61, p = 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF-beta expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.
Pilette
Charles
C
Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, U.K.
Nouri-Aria
Kayhan T
KT
Jacobson
Mikila R
MR
Wilcock
Louisa K
LK
Detry
Bruno
B
Walker
Samantha M
SM
Francis
James N
JN
Durham
Stephen R
SR
D000328:Adult; D000485:Allergens / Q000032:analysis / Q000276:immunology / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007167:Immunotherapy; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009297:Nasal Mucosa / Q000737:chemistry / Q000276:immunology*; D010940:Plant Proteins / Q000032:analysis / Q000276:immunology / Q000627:therapeutic use*; D006109:Poaceae; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D000485:Allergens; D000906:Antibodies; D007070:Immunoglobulin A; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007073:Immunoglobulin E