Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK

S K Witting Christensen, I Kortekaas Krohn, J Thuraiaiyah, T Skjold, J M Schmid, H J H Hoffmann

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.

METHODS: We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10).

RESULTS: Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05).

CONCLUSION: Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation.

OriginalsprogEngelsk
TidsskriftAllergy
Vol/bind69
Udgave nummer10
Sider (fra-til)1343-9
Antal sider7
ISSN0105-4538
DOI
StatusUdgivet - okt. 2014

Fingeraftryk

Allergens
Poaceae
Pyroglyphidae

Citer dette

Witting Christensen, S. K., Kortekaas Krohn, I., Thuraiaiyah, J., Skjold, T., Schmid, J. M., & Hoffmann, H. J. H. (2014). Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK. Allergy, 69(10), 1343-9. https://doi.org/10.1111/all.12482
Witting Christensen, S K ; Kortekaas Krohn, I ; Thuraiaiyah, J ; Skjold, T ; Schmid, J M ; Hoffmann, H J H. / Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK. I: Allergy. 2014 ; Bind 69, Nr. 10. s. 1343-9.
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title = "Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK",
abstract = "BACKGROUND: Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.METHODS: We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10).RESULTS: Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0{\%} (66.3-88.8) to 35.4{\%} (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6{\%} activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4{\%} activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1{\%} (15.6-92.8) to 26.1{\%} (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05).CONCLUSION: Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation.",
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month = "10",
doi = "10.1111/all.12482",
language = "English",
volume = "69",
pages = "1343--9",
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Witting Christensen, SK, Kortekaas Krohn, I, Thuraiaiyah, J, Skjold, T, Schmid, JM & Hoffmann, HJH 2014, 'Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK', Allergy, bind 69, nr. 10, s. 1343-9. https://doi.org/10.1111/all.12482

Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK. / Witting Christensen, S K; Kortekaas Krohn, I; Thuraiaiyah, J; Skjold, T; Schmid, J M; Hoffmann, H J H.

I: Allergy, Bind 69, Nr. 10, 10.2014, s. 1343-9.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK

AU - Witting Christensen, S K

AU - Kortekaas Krohn, I

AU - Thuraiaiyah, J

AU - Skjold, T

AU - Schmid, J M

AU - Hoffmann, H J H

N1 - © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2014/10

Y1 - 2014/10

N2 - BACKGROUND: Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.METHODS: We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10).RESULTS: Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05).CONCLUSION: Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation.

AB - BACKGROUND: Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.METHODS: We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10).RESULTS: Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05).CONCLUSION: Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation.

KW - Adult

KW - Basophil Degranulation Test

KW - Basophils/immunology

KW - Desensitization, Immunologic

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Poaceae/immunology

KW - Rhinitis, Allergic, Seasonal/immunology

KW - Young Adult

KW - p38 Mitogen-Activated Protein Kinases/immunology

U2 - 10.1111/all.12482

DO - 10.1111/all.12482

M3 - Journal article

VL - 69

SP - 1343

EP - 1349

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 10

ER -