A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

Kusumam Joseph, Sonia Bains, Baby G Tholanikunnel, Anette Bygum, Anne Aabom, Claus Koch, Henriette Farkas, Lilian Varga, Berhane Ghebrehiwet, Allen P Kaplan

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable.

METHODS: ELISA assays were developed using biotinylated activated factor XII (factor XIIa) or biotinylated kallikrein bound to avidin-coated plates. Incubation with plasma was followed by detection of bound C1-INH.

RESULTS: After standard curves were developed for quantification of C1-INH, serial dilutions of normal plasma were employed to validate the ability to detect known concentration of C1-INH in the plasma as a percent of normal. HAE types I and II were then tested. The level of functional C1-INH in all HAE types I and II plasma tested were less than 40% of our normal control. This was evident regardless whether we measured factor XIIa-C1-INH or kallikrein-C1-INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed levels of C1-INH between 0 and 57% of normal (mean, 38%) and 42 samples were considered equivocal (4 controls and 38 patients).

CONCLUSIONS: Diagnosis of HAE types I and II can be ascertained by inhibition of enzymes of the bradykinin-forming cascade; namely, factor XIIa and kallikrein. Either method yields functional C1-INH levels in HAE patients (types I & II) that are clearly abnormal with less variance or uncertainty than the commercial method. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftAllergy
Vol/bind70
Udgave nummer1
Sider (fra-til)115-119
ISSN0105-4538
DOI
StatusUdgivet - 2015

Fingeraftryk

Factor XIIa
Enzymes
Hereditary Angioedema Types I and II
Uncertainty

Citer dette

Joseph, K., Bains, S., Tholanikunnel, B. G., Bygum, A., Aabom, A., Koch, C., ... Kaplan, A. P. (2015). A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes. Allergy, 70(1), 115-119. https://doi.org/10.1111/all.12520
Joseph, Kusumam ; Bains, Sonia ; Tholanikunnel, Baby G ; Bygum, Anette ; Aabom, Anne ; Koch, Claus ; Farkas, Henriette ; Varga, Lilian ; Ghebrehiwet, Berhane ; Kaplan, Allen P. / A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes. I: Allergy. 2015 ; Bind 70, Nr. 1. s. 115-119.
@article{da2392ec2b7e4897892da8c45f0a7881,
title = "A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes",
abstract = "BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable.METHODS: ELISA assays were developed using biotinylated activated factor XII (factor XIIa) or biotinylated kallikrein bound to avidin-coated plates. Incubation with plasma was followed by detection of bound C1-INH.RESULTS: After standard curves were developed for quantification of C1-INH, serial dilutions of normal plasma were employed to validate the ability to detect known concentration of C1-INH in the plasma as a percent of normal. HAE types I and II were then tested. The level of functional C1-INH in all HAE types I and II plasma tested were less than 40{\%} of our normal control. This was evident regardless whether we measured factor XIIa-C1-INH or kallikrein-C1-INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed levels of C1-INH between 0 and 57{\%} of normal (mean, 38{\%}) and 42 samples were considered equivocal (4 controls and 38 patients).CONCLUSIONS: Diagnosis of HAE types I and II can be ascertained by inhibition of enzymes of the bradykinin-forming cascade; namely, factor XIIa and kallikrein. Either method yields functional C1-INH levels in HAE patients (types I & II) that are clearly abnormal with less variance or uncertainty than the commercial method. This article is protected by copyright. All rights reserved.",
author = "Kusumam Joseph and Sonia Bains and Tholanikunnel, {Baby G} and Anette Bygum and Anne Aabom and Claus Koch and Henriette Farkas and Lilian Varga and Berhane Ghebrehiwet and Kaplan, {Allen P}",
note = "This article is protected by copyright. All rights reserved.",
year = "2015",
doi = "10.1111/all.12520",
language = "English",
volume = "70",
pages = "115--119",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
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Joseph, K, Bains, S, Tholanikunnel, BG, Bygum, A, Aabom, A, Koch, C, Farkas, H, Varga, L, Ghebrehiwet, B & Kaplan, AP 2015, 'A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes', Allergy, bind 70, nr. 1, s. 115-119. https://doi.org/10.1111/all.12520

A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes. / Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G; Bygum, Anette; Aabom, Anne; Koch, Claus; Farkas, Henriette; Varga, Lilian; Ghebrehiwet, Berhane; Kaplan, Allen P.

I: Allergy, Bind 70, Nr. 1, 2015, s. 115-119.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

AU - Joseph, Kusumam

AU - Bains, Sonia

AU - Tholanikunnel, Baby G

AU - Bygum, Anette

AU - Aabom, Anne

AU - Koch, Claus

AU - Farkas, Henriette

AU - Varga, Lilian

AU - Ghebrehiwet, Berhane

AU - Kaplan, Allen P

N1 - This article is protected by copyright. All rights reserved.

PY - 2015

Y1 - 2015

N2 - BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable.METHODS: ELISA assays were developed using biotinylated activated factor XII (factor XIIa) or biotinylated kallikrein bound to avidin-coated plates. Incubation with plasma was followed by detection of bound C1-INH.RESULTS: After standard curves were developed for quantification of C1-INH, serial dilutions of normal plasma were employed to validate the ability to detect known concentration of C1-INH in the plasma as a percent of normal. HAE types I and II were then tested. The level of functional C1-INH in all HAE types I and II plasma tested were less than 40% of our normal control. This was evident regardless whether we measured factor XIIa-C1-INH or kallikrein-C1-INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed levels of C1-INH between 0 and 57% of normal (mean, 38%) and 42 samples were considered equivocal (4 controls and 38 patients).CONCLUSIONS: Diagnosis of HAE types I and II can be ascertained by inhibition of enzymes of the bradykinin-forming cascade; namely, factor XIIa and kallikrein. Either method yields functional C1-INH levels in HAE patients (types I & II) that are clearly abnormal with less variance or uncertainty than the commercial method. This article is protected by copyright. All rights reserved.

AB - BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable.METHODS: ELISA assays were developed using biotinylated activated factor XII (factor XIIa) or biotinylated kallikrein bound to avidin-coated plates. Incubation with plasma was followed by detection of bound C1-INH.RESULTS: After standard curves were developed for quantification of C1-INH, serial dilutions of normal plasma were employed to validate the ability to detect known concentration of C1-INH in the plasma as a percent of normal. HAE types I and II were then tested. The level of functional C1-INH in all HAE types I and II plasma tested were less than 40% of our normal control. This was evident regardless whether we measured factor XIIa-C1-INH or kallikrein-C1-INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed levels of C1-INH between 0 and 57% of normal (mean, 38%) and 42 samples were considered equivocal (4 controls and 38 patients).CONCLUSIONS: Diagnosis of HAE types I and II can be ascertained by inhibition of enzymes of the bradykinin-forming cascade; namely, factor XIIa and kallikrein. Either method yields functional C1-INH levels in HAE patients (types I & II) that are clearly abnormal with less variance or uncertainty than the commercial method. This article is protected by copyright. All rights reserved.

U2 - 10.1111/all.12520

DO - 10.1111/all.12520

M3 - Journal article

VL - 70

SP - 115

EP - 119

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 1

ER -