Immune cell phenotype and functional defects in Netherton syndrome

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dc.contributor University of Helsinki, Faculty of Medicine en
dc.contributor University of Helsinki, Integrins in immunity en
dc.contributor University of Helsinki, Department of Ophthalmology and Otorhinolaryngology en
dc.contributor University of Helsinki, Department of Clinical Chemistry and Hematology en
dc.contributor University of Helsinki, Children's Hospital en
dc.contributor University of Helsinki, Department of Clinical Chemistry and Hematology en
dc.contributor University of Helsinki, Department of Dermatology, Allergology and Venereology en
dc.contributor University of Helsinki, Department of Dermatology, Allergology and Venereology en
dc.contributor.author Eränkö, Elina
dc.contributor.author Ilander, Mette
dc.contributor.author Tuomiranta, Mirja
dc.contributor.author Mäkitie, Antti
dc.contributor.author Lassila, Tea
dc.contributor.author Kreutzman, Anna
dc.contributor.author Klemetti, Paula
dc.contributor.author Mustjoki, Satu
dc.contributor.author Hannula-Jouppi, Katariina
dc.contributor.author Ranki, Annamari
dc.date.accessioned 2018-12-17T14:04:01Z
dc.date.available 2018-12-17T14:04:01Z
dc.date.issued 2018-11-26
dc.identifier.citation Eränkö , E , Ilander , M , Tuomiranta , M , Mäkitie , A , Lassila , T , Kreutzman , A , Klemetti , P , Mustjoki , S , Hannula-Jouppi , K & Ranki , A 2018 , ' Immune cell phenotype and functional defects in Netherton syndrome ' , Orphanet journal of rare diseases , vol. 13 , 213 . https://doi.org/10.1186/s13023-018-0956-6 en
dc.identifier.issn 1750-1172
dc.identifier.other PURE: 120231627
dc.identifier.other PURE UUID: 8f7ae094-bd55-41fc-b204-7f30855fdccf
dc.identifier.other WOS: 000451349900003
dc.identifier.other Scopus: 85057223034
dc.identifier.other ORCID: /0000-0002-0816-8241/work/51806764
dc.identifier.uri http://hdl.handle.net/10138/276991
dc.description.abstract BackgroundNetherton syndrome (NS) is a rare life-threatening syndrome caused by SPINK5 mutations leading to a skin barrier defect and a severe atopic diathesis. NS patients are prone to bacterial infections, but the understanding of the underlying immune deficiency is incomplete.ResultsWe analyzed blood lymphocyte phenotypes and function in relation to clinical infections in 11 Finnish NS patients, aged 3 to 17years, and healthy age-matched controls. The proportion of B cells (CD19(+)) and naive B cells (CD27(-), IgD(+)) were high while memory B cells (CD27(+)) and switched memory B cells (CD27(+)IgM(-)IgD(-)), crucial for the secondary response to pathogens, was below or in the lowest quartile of the reference values in 8/11 (73%) and 9/11 (82%) patients, respectively. The proportion of activated non-differentiated B cells (CD21(low), CD38l(ow)) was below or in the lowest quartile of the reference values in 10/11 (91%) patients. Despite normal T cell counts, the proportion of naive CD4(+) T cells was reduced significantly and the proportion of CD8(+) T central memory significantly elevated. An increased proportion of CD57(+) CD8(+) T cells indicated increased differentiation potential of the T cells. The proportion of cytotoxic NK cells was elevated in NS patients in phenotypic analysis based on CD56DIM, CD16(+) and CD27(-) NK cells but in functional analysis, decreased expression of CD107a/b indicated impaired cytotoxicity.The T and NK cell phenotype seen in NS patients also significantly differed from that of age-matched atopic dermatitis (AD) patients, indicating a distinctive profile in NS. The frequency of skin infections correlated with the proportion of CD62L(+) T cells, naive CD4(+) and CD27(+) CD8(+) T cells and with activated B cells. Clinically beneficial intravenous immunoglobulin therapy (IVIG) increased naive T cells and terminal differentiated effector memory CD8(+) cells and decreased the proportion of activated B cells and plasmablasts in three patients studied.ConclusionsThis study shows novel quantitative and functional aberrations in several lymphocyte subpopulations, which correlate with the frequency of infections in patients with Netherton syndrome. IVIG therapy normalized some dysbalancies and was clinically beneficial. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof Orphanet journal of rare diseases
dc.rights en
dc.subject Netherton syndrome en
dc.subject T cell en
dc.subject B cell en
dc.subject NK cell en
dc.subject Cytotoxicity en
dc.subject Cytokine en
dc.subject Immunoglobulin therapy en
dc.subject NATURAL-KILLER-CELLS en
dc.subject T-CELL en
dc.subject SPINK5 en
dc.subject CD27 en
dc.subject 3111 Biomedicine en
dc.title Immune cell phenotype and functional defects in Netherton syndrome en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1186/s13023-018-0956-6
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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