Immune cell phenotype and functional defects in Netherton syndrome

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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 .

Title: Immune cell phenotype and functional defects in Netherton syndrome
Author: Eränkö, Elina; Ilander, Mette; Tuomiranta, Mirja; Mäkitie, Antti; Lassila, Tea; Kreutzman, Anna; Klemetti, Paula; Mustjoki, Satu; Hannula-Jouppi, Katariina; Ranki, Annamari
Contributor organization: Faculty of Medicine
Department of Dermatology, Allergology and Venereology
University of Helsinki
Integrins in immunity
External Funding
Department of Clinical Chemistry and Hematology
Hematologian yksikkö
Department of Ophthalmology and Otorhinolaryngology
Department of Oncology
Children's Hospital
Research Programs Unit
Research Programme for Molecular Neurology
HUS Children and Adolescents
HUS Head and Neck Center
HUS Comprehensive Cancer Center
HUS Inflammation Center
Date: 2018-11-26
Language: eng
Number of pages: 10
Belongs to series: Orphanet journal of rare diseases
ISSN: 1750-1172
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.
Subject: Netherton syndrome
T cell
B cell
NK cell
Immunoglobulin therapy
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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