Changes in humoral responses to β-lactoglobulin in tolerant patients suggest a particular role for IgG4 in delayed, non-IgE-mediated cow's milk allergy

Authors: Sletten, Gaynour B. G.; Halvorsen, Ragnhild1; Egaas, Eliann2; Halstensen, Trond S.

Source: Pediatric Allergy and Immunology, Volume 17, Number 6, September 2006 , pp. 435-443(9)

Publisher: Blackwell Publishing

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Abstract:

Sletten GBG, Halvorsen R, Egaas E, Halstensen TS. Changes in humoral responses to β-lactoglobulin in tolerant patients suggest a particular role for IgG4 in delayed, non-IgE-mediated cow's milk allergy.

Pediatr Allergy Immunol 2006: 17: 435-443. © 2006 The Authors Journal compilation © 2006 Blackwell Munksgaard

The major cow's milk allergen β-lactoglobulin (β-LG) is relatively resistant to enzymatic degradation and may therefore be involved in non-immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) with delayed gastrointestinal symptoms. Serum levels of β-LG-specific IgG1, IgG4, IgE, and IgA were compared in clinically reactive and tolerized IgE-mediated and non-IgE-mediated CMA with delayed gastrointestinal symptoms (n = 29) and controls (n = 10). Tolerance was associated with decreased β-LG-specific IgE, IgG1, and IgG4 levels in both patient groups. However, the significantly increased β-LG-specific IgG4 levels in clinically reactive non-IgE-mediated CMA patients, and its median 36-fold reduction in tolerant patients, suggested a possible immunopathological role for IgG4 in delayed CMA. Similarly, the significantly increased β-LG-specific IgE levels in IgE-mediated CMA patients were decreased 44-fold in tolerant patients. The tolerant patients had apparently shifted the humoral immune response from a β-LG-specific IgE- and/or IgG4-dominated immune response to an IgA-dominated immune response as the IgA/IgE or IgA/IgG4 ratios increased 90- and 15-fold in tolerant IgE-mediated-, and non-IgE-mediated CMA patients, respectively. Thus, the marked difference in β-LG-specific Ig ratios suggested a tolerance-induced inhibition of a Th2-type of immune response with significantly increased IgA dominance in both CMA patient groups.

Keywords: cow's milk protein; immunoglobulins

Document Type: Research article

DOI: 10.1111/j.1399-3038.2006.00408.x

Affiliations: 1: Voksentoppen Centre for Asthma and Allergy, Oslo, Norway 2: National Veterinary Institute, Oslo, Norway

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