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Mast cell chymase: a useful serum marker in anaphylaxis

Mast cell chymase: a useful serum marker in anaphylaxis
Mast cell chymase: a useful serum marker in anaphylaxis
RATIONALE: The reliable diagnosis of anaphylaxis can present challenge. We have explored mast cell chymase as a potential marker for anaphylaxis.

METHODS: A sandwich-based ELISA was developed with monoclonal antibodies we have prepared against chymase, and validated for application to serum samples. The enzymatic activity of chymase was determined in parallel using the chromogenic substrates suc-AAPF-pNA and RETF-4NA. Tryptase, carboxypeptidase and DPPI were measured by ELISA. Serum was collected from cases of anaphylaxis provoked by food, drug and insect stings (n=181); from healthy blood donors (n=123); and from patients allergic to food (n=76) or drugs (n=26).

RESULTS: The ELISA allowed detection of chymase in all serum samples, and values obtained were unaffected by the presence of alpha-2-macroglobulin or other inhibitors. Chymase levels in serum collected from patients within 8h of anaphylaxis were greater than those in the control group (p=0.0069); and concentrations remained high at least 24h after onset of the reaction. Chymase levels in anaphylaxis correlated with levels of mast cell carboxypeptidase and with dipeptidyl peptidase 1 (DPPI), but not tryptase. Concentrations of chymase measured by ELISA were weakly associated with serum chymase activity. Addition of DPPI to serum increased the chymase activity in samples collected prior to allergen challenge (p=0.0008) consistent with the presence of pro-forms of chymase in the circulation. However, DPPI-induced increases in serum chymase activity were not observed in samples collected following a reaction (when serum DPPI concentrations were elevated).

CONCLUSIONS: Measurement of mast cell chymase in serum should be useful as a means for laboratory confirmation of anaphylaxis.
0091-6749
AB143
Zhou, X.
84558a96-3129-44de-b295-869d9ee4d19f
Whitworth, H.S.
920dc983-f88e-4afe-99d4-c3440d4ade94
E-Khedr, M.
37c876ff-7226-4d51-bd20-dfe0bbca3d73
Brown, T.A.
8fe60c1d-d67f-4156-a5ec-638c12290753
Goswami, R.
64e8d1fe-46a3-4ace-acdd-c6ee900a1087
Eren, E.
7a11b792-2ebb-47f0-aca7-3d2f5e87e129
Lucas, J.A.
5cb3546c-87b2-4e59-af48-402076e25313
Erlewyn-Lajeunesse, M.D.S.
e1763b6d-165b-45c5-9108-5dc8722220b9
Summers, C.W.
00ef86a6-37b5-4f07-822b-534a5a9c161b
Pumphrey, R.S.H.
da8e3ec1-be1d-4fdf-a28d-f759d48bb3e5
Wild, G.
b059ab6a-087e-499b-a38c-327182b56e33
Pedersen, J.
4e08a1a9-a4ad-4614-bc62-77560d53f153
Walls, A.F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Zhou, X.
84558a96-3129-44de-b295-869d9ee4d19f
Whitworth, H.S.
920dc983-f88e-4afe-99d4-c3440d4ade94
E-Khedr, M.
37c876ff-7226-4d51-bd20-dfe0bbca3d73
Brown, T.A.
8fe60c1d-d67f-4156-a5ec-638c12290753
Goswami, R.
64e8d1fe-46a3-4ace-acdd-c6ee900a1087
Eren, E.
7a11b792-2ebb-47f0-aca7-3d2f5e87e129
Lucas, J.A.
5cb3546c-87b2-4e59-af48-402076e25313
Erlewyn-Lajeunesse, M.D.S.
e1763b6d-165b-45c5-9108-5dc8722220b9
Summers, C.W.
00ef86a6-37b5-4f07-822b-534a5a9c161b
Pumphrey, R.S.H.
da8e3ec1-be1d-4fdf-a28d-f759d48bb3e5
Wild, G.
b059ab6a-087e-499b-a38c-327182b56e33
Pedersen, J.
4e08a1a9-a4ad-4614-bc62-77560d53f153
Walls, A.F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe

Zhou, X., Whitworth, H.S., E-Khedr, M., Brown, T.A., Goswami, R., Eren, E., Lucas, J.A., Erlewyn-Lajeunesse, M.D.S., Summers, C.W., Pumphrey, R.S.H., Wild, G., Pedersen, J. and Walls, A.F. (2011) Mast cell chymase: a useful serum marker in anaphylaxis. Journal of Allergy and Clinical Immunology, 127 (2), AB143. (doi:10.1016/j.jaci.2010.12.566).

Record type: Meeting abstract

Abstract

RATIONALE: The reliable diagnosis of anaphylaxis can present challenge. We have explored mast cell chymase as a potential marker for anaphylaxis.

METHODS: A sandwich-based ELISA was developed with monoclonal antibodies we have prepared against chymase, and validated for application to serum samples. The enzymatic activity of chymase was determined in parallel using the chromogenic substrates suc-AAPF-pNA and RETF-4NA. Tryptase, carboxypeptidase and DPPI were measured by ELISA. Serum was collected from cases of anaphylaxis provoked by food, drug and insect stings (n=181); from healthy blood donors (n=123); and from patients allergic to food (n=76) or drugs (n=26).

RESULTS: The ELISA allowed detection of chymase in all serum samples, and values obtained were unaffected by the presence of alpha-2-macroglobulin or other inhibitors. Chymase levels in serum collected from patients within 8h of anaphylaxis were greater than those in the control group (p=0.0069); and concentrations remained high at least 24h after onset of the reaction. Chymase levels in anaphylaxis correlated with levels of mast cell carboxypeptidase and with dipeptidyl peptidase 1 (DPPI), but not tryptase. Concentrations of chymase measured by ELISA were weakly associated with serum chymase activity. Addition of DPPI to serum increased the chymase activity in samples collected prior to allergen challenge (p=0.0008) consistent with the presence of pro-forms of chymase in the circulation. However, DPPI-induced increases in serum chymase activity were not observed in samples collected following a reaction (when serum DPPI concentrations were elevated).

CONCLUSIONS: Measurement of mast cell chymase in serum should be useful as a means for laboratory confirmation of anaphylaxis.

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More information

e-pub ahead of print date: 19 February 2011
Published date: February 2011

Identifiers

Local EPrints ID: 432869
URI: http://eprints.soton.ac.uk/id/eprint/432869
ISSN: 0091-6749
PURE UUID: fce2e970-d3ce-41da-a268-5ef645ecf3d4
ORCID for M. E-Khedr: ORCID iD orcid.org/0000-0001-9942-4409
ORCID for M.D.S. Erlewyn-Lajeunesse: ORCID iD orcid.org/0000-0003-1982-1397
ORCID for A.F. Walls: ORCID iD orcid.org/0000-0003-4803-4595

Catalogue record

Date deposited: 31 Jul 2019 16:30
Last modified: 10 Nov 2021 03:53

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Contributors

Author: X. Zhou
Author: H.S. Whitworth
Author: M. E-Khedr ORCID iD
Author: T.A. Brown
Author: R. Goswami
Author: E. Eren
Author: J.A. Lucas
Author: M.D.S. Erlewyn-Lajeunesse ORCID iD
Author: C.W. Summers
Author: R.S.H. Pumphrey
Author: G. Wild
Author: J. Pedersen
Author: A.F. Walls ORCID iD

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