Th2-skewed T cells correlate with B cell response to α-Gal and tick antigens in α-Gal syndrome
Danijela Apostolovic, … , Staffan Paulie, Marianne van Hage
Danijela Apostolovic, … , Staffan Paulie, Marianne van Hage
Published January 26, 2023
Citation Information: J Clin Invest. 2023;133(6):e158357. https://doi.org/10.1172/JCI158357.
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Research Article Immunology

Th2-skewed T cells correlate with B cell response to α-Gal and tick antigens in α-Gal syndrome

Abstract

Tick bites have been shown to transmit a novel form of severe food allergy, the galactose-α-1,3-galactose (α-Gal) syndrome (AGS). Cellular responses to α-Gal in patients with AGS have, to date, not been thoroughly scrutinized. Therefore, we investigated T and B cell proliferation, activation, and cytokine profiles in response to tick protein extract (TE) and α-Gal-free TE in patients with AGS and in healthy controls. T and B cells from both patients and controls proliferated in response to TE, but significantly more in patients with AGS. B cell proliferation, but not T cell proliferation, in patients with AGS was reduced by removing α-Gal from the TE. In addition, TE induced a clear Th2 cytokine profile in patients with AGS. Expression of CD23 by B cells correlated only to T cell proliferation. However, both B cell proliferation and CD23 expression were reduced when CD40L and IL-4 were blocked. A large portion of the IgG1 and IgE antibodies binding TE in patients with AGS were directed against the α-Gal epitope. We have, for what we believe to be the first time, investigated T and B cell responses to α-Gal carrying tick proteins in patients with AGS, which will be essential for the understanding of the immune response against an allergenic carbohydrate transmitted by ticks.

Authors

Danijela Apostolovic, Jeanette Grundström, Mensiena B. Gea Kiewiet, Marija Perusko, Carl Hamsten, Maria Starkhammar, Staffan Paulie, Marianne van Hage

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Figure 4

B cell expression of CD23.

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B cell expression of CD23. (A) Gating strategy for CD23-expressing B cel...
(A) Gating strategy for CD23-expressing B cells. (B) CD23 expression in unstimulated compared with TE stimulated B cells in patients with AGS (left, n = 30) and healthy controls (right, n = 18), Wilcoxon matched-pairs signed rank test, ***P < 0.001. (C) Comparison of patients with AGS and healthy controls, Mann-Whitney U test, *P < 0.05, n = 30 (AGS) and n = 18 (controls). (D) Effect of inhibition with anti-CD40L and anti-IL-4 antibodies in patients with AGS, Friedman test with Dunn’s multiple comparisons test, **P < 0.01, ***P < 0.001, n = 19. (E) Effect of removing α-Gal from the TE in patients with AGS (left, n = 9), and healthy controls (right, n = 13), Wilcoxon matched-pairs signed rank test, **P < 0.01. (F) Comparison of CD23 expression in unstimulated B cells compared with B cells stimulated with an α-Gal containing nontick protein in patients with AGS (left, n = 21) and healthy controls (right, n = 15). (G) Comparison of CD23 expression by naive (CD27-IgD+) and memory (CD27+) B cells after TE stimulation in patients with AGS, Wilcoxon matched-pairs signed rank test, ***P < 0.001, n = 17. Each point within the box plot represents 1 individual. Box plots represent IQR and median, whiskers extend to the farthest data points. (H) Correlation of T cell proliferation and CD23 expression in response to TE in patients with AGS, Spearman’s rank correlation, ρ = 0.792, P < 0.001, n = 19. Each point represents 1 individual.