Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause

Detalhes bibliográficos
Autor(a) principal: Santo, GC
Data de Publicação: 2018
Outros Autores: Baldeiras, I, Guerreiro, R, Ribeiro, JA, Cunha, R, Youngstein, T, Nanthapisal, S, Leitão, J, Fernandes, C, Caramelo, F, Almeida, MR, Brás, J, Santana, I
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.4/2249
Resumo: BACKGROUND: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). METHODS: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. RESULTS: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. CONCLUSION: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.
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spelling Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown CauseAdenosina DesaminaseImunoglobulina MBiomarcadoresSíndrome de SneddonBACKGROUND: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). METHODS: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. RESULTS: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. CONCLUSION: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.RIHUCSanto, GCBaldeiras, IGuerreiro, RRibeiro, JACunha, RYoungstein, TNanthapisal, SLeitão, JFernandes, CCaramelo, FAlmeida, MRBrás, JSantana, I2019-08-22T15:00:04Z20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.4/2249engCerebrovasc Dis. 2018;46(5-6):257-264.10.1159/000495794info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-11T14:23:38Zoai:rihuc.huc.min-saude.pt:10400.4/2249Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:04:42.949954Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
title Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
spellingShingle Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
Santo, GC
Adenosina Desaminase
Imunoglobulina M
Biomarcadores
Síndrome de Sneddon
title_short Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
title_full Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
title_fullStr Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
title_full_unstemmed Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
title_sort Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause
author Santo, GC
author_facet Santo, GC
Baldeiras, I
Guerreiro, R
Ribeiro, JA
Cunha, R
Youngstein, T
Nanthapisal, S
Leitão, J
Fernandes, C
Caramelo, F
Almeida, MR
Brás, J
Santana, I
author_role author
author2 Baldeiras, I
Guerreiro, R
Ribeiro, JA
Cunha, R
Youngstein, T
Nanthapisal, S
Leitão, J
Fernandes, C
Caramelo, F
Almeida, MR
Brás, J
Santana, I
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv RIHUC
dc.contributor.author.fl_str_mv Santo, GC
Baldeiras, I
Guerreiro, R
Ribeiro, JA
Cunha, R
Youngstein, T
Nanthapisal, S
Leitão, J
Fernandes, C
Caramelo, F
Almeida, MR
Brás, J
Santana, I
dc.subject.por.fl_str_mv Adenosina Desaminase
Imunoglobulina M
Biomarcadores
Síndrome de Sneddon
topic Adenosina Desaminase
Imunoglobulina M
Biomarcadores
Síndrome de Sneddon
description BACKGROUND: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). METHODS: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. RESULTS: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. CONCLUSION: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01T00:00:00Z
2019-08-22T15:00:04Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.4/2249
url http://hdl.handle.net/10400.4/2249
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cerebrovasc Dis. 2018;46(5-6):257-264.
10.1159/000495794
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