Serum complexes between C1INH and C1INH autoantibodies for the diagnosis of acquired angioedema
(2019) In Clinical and Experimental Immunology 198(3). p.341-350- Abstract
Acquired angioedema due to C1-inhibitor (C1INH) deficiency (AAE) is caused by secondary C1INH deficiency leading to bradykinin-mediated angioedema episodes. AAE typically presents in adulthood and is associated with B cell lymphoproliferation. Anti-C1INH autoantibodies (antiC1INHAbs) are detectable in a subset of AAE cases and considered a hallmark of the disease. When free antiC1INHAbs and malignant tumors are not detectable, diagnosis relies on the finding of low C1INH levels and/or function, lack of family history and SERPING1 mutations, age at onset and low or undetectable C1q levels, none of which is specific for AAE. We tested the diagnostic value of a novel enzyme-linked immunosorbent assay (ELISA) for the detection of... (More)
Acquired angioedema due to C1-inhibitor (C1INH) deficiency (AAE) is caused by secondary C1INH deficiency leading to bradykinin-mediated angioedema episodes. AAE typically presents in adulthood and is associated with B cell lymphoproliferation. Anti-C1INH autoantibodies (antiC1INHAbs) are detectable in a subset of AAE cases and considered a hallmark of the disease. When free antiC1INHAbs and malignant tumors are not detectable, diagnosis relies on the finding of low C1INH levels and/or function, lack of family history and SERPING1 mutations, age at onset and low or undetectable C1q levels, none of which is specific for AAE. We tested the diagnostic value of a novel enzyme-linked immunosorbent assay (ELISA) for the detection of circulating complexes between C1INH and antiC1INHAbs (C1INH–antiC1INHAb) in the serum of 20 European AAE patients characterized on the basis of their complement levels and function. Free antiC1INHAbs were detected in nine of 20 patients [six of immunoglobulin (Ig)G class, two of IgM class and one simultaneously presenting IgG and IgM classes], whereas C1INH–antiC1INHAb complexes were found in 18 of 20 of the AAE cases, regardless of the presence or absence of detectable free anti-C1INHAbs. Of note, nine of 20 patients showed negative free antiC1INHabs, but positive C1INH–antiC1INHAb complexes in their first measurement. In the cohort presented, IgM-class C1INH–antiC1INHAb are specifically and strongly associated with low C1q serum levels. Detection of C1INH–antiC1-INHAbs provides an added value for AAE diagnosis, especially in those cases in whom no free anti-C1INH antibodies are detected. The link between IgM-class C1INH–antiC1INHAb complexes and C1q consumption could have further implications for the development of autoimmune manifestations in AAE.
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- author
- López-Lera, A. ; Garrido, S. ; Nozal, P. ; Skatum, L. LU ; Bygum, A. ; Caballero, T. and López Trascasa, M.
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- acquired angioedema, autoantibody, diagnosis, ELISA, immune complex
- in
- Clinical and Experimental Immunology
- volume
- 198
- issue
- 3
- pages
- 10 pages
- publisher
- British Society for Immunology
- external identifiers
-
- scopus:85075091693
- pmid:31397881
- ISSN
- 0009-9104
- DOI
- 10.1111/cei.13361
- language
- English
- LU publication?
- no
- id
- 5c81749a-580e-42ae-b5e6-f20001a553ba
- date added to LUP
- 2019-11-28 13:36:17
- date last changed
- 2024-05-29 04:32:15
@article{5c81749a-580e-42ae-b5e6-f20001a553ba,
abstract = {{<p>Acquired angioedema due to C1-inhibitor (C1INH) deficiency (AAE) is caused by secondary C1INH deficiency leading to bradykinin-mediated angioedema episodes. AAE typically presents in adulthood and is associated with B cell lymphoproliferation. Anti-C1INH autoantibodies (antiC1INHAbs) are detectable in a subset of AAE cases and considered a hallmark of the disease. When free antiC1INHAbs and malignant tumors are not detectable, diagnosis relies on the finding of low C1INH levels and/or function, lack of family history and SERPING1 mutations, age at onset and low or undetectable C1q levels, none of which is specific for AAE. We tested the diagnostic value of a novel enzyme-linked immunosorbent assay (ELISA) for the detection of circulating complexes between C1INH and antiC1INHAbs (C1INH–antiC1INHAb) in the serum of 20 European AAE patients characterized on the basis of their complement levels and function. Free antiC1INHAbs were detected in nine of 20 patients [six of immunoglobulin (Ig)G class, two of IgM class and one simultaneously presenting IgG and IgM classes], whereas C1INH–antiC1INHAb complexes were found in 18 of 20 of the AAE cases, regardless of the presence or absence of detectable free anti-C1INHAbs. Of note, nine of 20 patients showed negative free antiC1INHabs, but positive C1INH–antiC1INHAb complexes in their first measurement. In the cohort presented, IgM-class C1INH–antiC1INHAb are specifically and strongly associated with low C1q serum levels. Detection of C1INH–antiC1-INHAbs provides an added value for AAE diagnosis, especially in those cases in whom no free anti-C1INH antibodies are detected. The link between IgM-class C1INH–antiC1INHAb complexes and C1q consumption could have further implications for the development of autoimmune manifestations in AAE.</p>}},
author = {{López-Lera, A. and Garrido, S. and Nozal, P. and Skatum, L. and Bygum, A. and Caballero, T. and López Trascasa, M.}},
issn = {{0009-9104}},
keywords = {{acquired angioedema; autoantibody; diagnosis; ELISA; immune complex}},
language = {{eng}},
number = {{3}},
pages = {{341--350}},
publisher = {{British Society for Immunology}},
series = {{Clinical and Experimental Immunology}},
title = {{Serum complexes between C1INH and C1INH autoantibodies for the diagnosis of acquired angioedema}},
url = {{http://dx.doi.org/10.1111/cei.13361}},
doi = {{10.1111/cei.13361}},
volume = {{198}},
year = {{2019}},
}