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Open Access 01-12-2018 | Research

Immune cell phenotype and functional defects in Netherton syndrome

Authors: Elina Eränkö, Mette Ilander, Mirja Tuomiranta, Antti Mäkitie, Tea Lassila, Anna Kreutzman, Paula Klemetti, Satu Mustjoki, Katariina Hannula-Jouppi, Annamari Ranki

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

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 (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 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.

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Title: Immune cell phenotype and functional defects in Netherton syndrome
Authors: Elina Eränkö
Mette Ilander
Mirja Tuomiranta
Antti Mäkitie
Tea Lassila
Anna Kreutzman
Paula Klemetti
Satu Mustjoki
Katariina Hannula-Jouppi
Annamari Ranki
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-018-0956-6

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Immune cell phenotype and functional defects in Netherton syndrome

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Results

Conclusions

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