Immune cell phenotype and functional defects in Netherton syndrome

Show simple item record

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 2018-12-02T04:14:39Z
dc.date.available 2018-12-02T04:14:39Z
dc.date.issued 2018-11-26
dc.identifier.citation Orphanet Journal of Rare Diseases. 2018 Nov 26;13(1):213
dc.identifier.uri http://hdl.handle.net/10138/269349
dc.description.abstract Abstract Background Netherton 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. Results We analyzed blood lymphocyte phenotypes and function in relation to clinical infections in 11 Finnish NS patients, aged 3 to 17 years, and healthy age-matched controls. The proportion of B cells (CD19+) and naïve 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 (CD21low, CD38low) was below or in the lowest quartile of the reference values in 10/11 (91%) patients. Despite normal T cell counts, the proportion of naïve 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, naïve CD4+ and CD27+ CD8+ T cells and with activated B cells. Clinically beneficial intravenous immunoglobulin therapy (IVIG) increased naïve T cells and terminal differentiated effector memory CD8+ cells and decreased the proportion of activated B cells and plasmablasts in three patients studied. Conclusions This 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.
dc.publisher BioMed Central
dc.subject Netherton syndrome
dc.subject T cell
dc.subject B cell
dc.subject NK cell
dc.subject Cytotoxicity
dc.subject Cytokine
dc.subject Immunoglobulin therapy
dc.title Immune cell phenotype and functional defects in Netherton syndrome
dc.date.updated 2018-12-02T04:14:39Z
dc.language.rfc3066 en
dc.rights.holder The Author(s).
dc.type.uri http://purl.org/eprint/entityType/ScholarlyWork
dc.type.uri http://purl.org/eprint/entityType/Expression
dc.type.uri http://purl.org/eprint/type/JournalArticle

Files in this item

Total number of downloads: Loading...

Files Size Format View
13023_2018_Article_956.pdf 1.742Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record