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RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect.
McKenzie, Craig I; Varese, Nirupama; Aui, Pei Mun; Reinwald, Simone; Wines, Bruce D; Hogarth, P Mark; Thien, Francis; Hew, Mark; Rolland, Jennifer M; O'Hehir, Robyn E; van Zelm, Menno C.
Afiliação
  • McKenzie CI; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Varese N; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Aui PM; Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Reinwald S; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Wines BD; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Hogarth PM; Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Thien F; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Hew M; Immune Therapies Group, Burnet Institute, Melbourne, Victoria, Australia.
  • Rolland JM; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
  • O'Hehir RE; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • van Zelm MC; Immune Therapies Group, Burnet Institute, Melbourne, Victoria, Australia.
Allergy ; 78(3): 822-835, 2023 03.
Article em En | MEDLINE | ID: mdl-36153670
BACKGROUND: Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen-specific IgG4 . IgG4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B-cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen-specific Bmem subsets induced by SLIT for grass pollen allergy. METHODS: Blood samples were collected twice outside the pollen season from twenty-seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4-month pre-seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single-cell RNA sequencing was performed on FACS-purified Lol p 1-specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort. RESULTS: Four months of SLIT increased RGP-specific IgE and IgG4 in serum and induced two Lol p 1-specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG4 ), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1+ Bmem expressing surface IgG4 , CD23, and CD29 after SLIT. CONCLUSIONS: A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface-expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lolium / Rinite Alérgica Sazonal / Hipersensibilidade Limite: Humans Idioma: En Revista: Allergy Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lolium / Rinite Alérgica Sazonal / Hipersensibilidade Limite: Humans Idioma: En Revista: Allergy Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Austrália