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Induction of IgG2 and IgG4 B-cell memory following sublingual immunotherapy for ryegrass pollen allergy.

ABSTRACT: BACKGROUND:While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen-specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T-cell function and increased allergen-specific IgG4 , yet little is known about the effect on the memory B-cell compartment. OBJECTIVE:We aimed to examine the effects of AIT on the IgE- and IgG subclass-expressing memory B cells. METHODS:We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen-specific Ig levels. RESULTS:SLIT increased RGP-specific serum IgG2 and IgG4 , as well as the frequencies of IgG2 + and IgG4 + memory B cells, whereas no effect was observed on the IgE+ memory B-cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement. CONCLUSION:Our data provide evidence for immunological effects of SLIT on B-cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE-mediated allergic responses.

SUBMITTER: Heeringa JJ

PROVIDER: S-EPMC7317934 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Induction of IgG<sub>2</sub> and IgG<sub>4</sub> B-cell memory following sublingual immunotherapy for ryegrass pollen allergy.

Heeringa Jorn J JJ McKenzie Craig I CI Varese Nirupama N Hew Mark M Bakx Amy T C M ATCM Aui Pei M PM Rolland Jennifer M JM O'Hehir Robyn E RE van Zelm Menno C MC

Allergy 20191104 5

<h4>Background</h4>While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen-specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T-cell function and increased allergen-specific IgG<sub>4</sub> , yet little is known about the effect on the memory B-cell compartment.<h4> ...[more]

PMID: 31587307

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Project description:BackgroundOral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.ObjectiveWe sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy.MethodsWe randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.ResultsThirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.ConclusionOIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.

Dataset Information

Induction of IgG2 and IgG4 B-cell memory following sublingual immunotherapy for ryegrass pollen allergy.

Publications

Induction of IgG<sub>2</sub> and IgG<sub>4</sub> B-cell memory following sublingual immunotherapy for ryegrass pollen allergy.

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