Diversity in Serine/Threonine Protein Kinase-4 Deficiency and Review of the Literature.

Amyloidosis Atopy Cutaneous viral infections Isolated CD4 lymphopenia Juvenile idiopathic arthritis Leukocytoclastic vasculitis Lupus nephritis Lymphoma MST1 Mammalian Sterile 20-like Protein Kinase 1 STK4

Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
10 2021
Historique:
received: 03 01 2021
revised: 23 05 2021
accepted: 25 05 2021
pubmed: 20 6 2021
medline: 29 10 2021
entrez: 19 6 2021
Statut: ppublish

Résumé

Serine/threonine kinase-4 (STK4) deficiency is an autosomal recessive combined immunodeficiency. We aimed to define characteristic clinical and laboratory features to aid the differential diagnosis and determine the most suitable therapy. In addition to nine STK4 deficiency patients, we reviewed 15 patients from the medical literature. We compared B lymphocyte subgroups of the cohort with age-matched healthy controls. In the cohort, median age at symptom onset and age at diagnosis were 6 years 8 months (range, 6-248 months) and 7 years 5 months (range, 6-260 months), respectively. The main clinical findings were infections (in all nine patients [9 of 9]), autoimmune or inflammatory diseases (7 of 9), and atopy (4 of 9). CD4 lymphopenia (9 out 9), lymphopenia (7 out 9), intermittent eosinophilia (4 out 9), transient neutropenia (3 out 9), low IgM (4 out 9), and high IgE (4 out 9) were common. Decreased recent thymic emigrants, naive and central memory T cells, but increased effector memory T cells were present. The increase in plasmablasts (P = .003) and decrease in switched memory B cells (P = .022) were significant. When 24 patients are analyzed, cutaneous viral infections (n = 20), recurrent pneumonia (n = 18), Epstein Barr virus-associated lymphoproliferation (n = 11), atopic dermatitis (n = 10), autoimmune cytopenia (n = 7), and lymphoma (n = 6) were frequent. Lymphopenia, CD4 lymphopenia, high IgG, IgA, and IgE were common laboratory characteristics. The differential diagnosis with autosomal recessive hyper-IgE syndrome is crucial. Because, atopy and CD4 lymphopenia are common in both diseases. Immunoglobulins, antibacterial, and antiviral prophylaxis are the mainstays of treatment. Clinicians may use immunomodulatory therapies during inflammatory or autoimmune complications. However, more data are needed to recommend hematopoietic stem cell transplantation as a safe therapy.

Sections du résumé

BACKGROUND
Serine/threonine kinase-4 (STK4) deficiency is an autosomal recessive combined immunodeficiency.
OBJECTIVE
We aimed to define characteristic clinical and laboratory features to aid the differential diagnosis and determine the most suitable therapy.
METHODS
In addition to nine STK4 deficiency patients, we reviewed 15 patients from the medical literature. We compared B lymphocyte subgroups of the cohort with age-matched healthy controls.
RESULTS
In the cohort, median age at symptom onset and age at diagnosis were 6 years 8 months (range, 6-248 months) and 7 years 5 months (range, 6-260 months), respectively. The main clinical findings were infections (in all nine patients [9 of 9]), autoimmune or inflammatory diseases (7 of 9), and atopy (4 of 9). CD4 lymphopenia (9 out 9), lymphopenia (7 out 9), intermittent eosinophilia (4 out 9), transient neutropenia (3 out 9), low IgM (4 out 9), and high IgE (4 out 9) were common. Decreased recent thymic emigrants, naive and central memory T cells, but increased effector memory T cells were present. The increase in plasmablasts (P = .003) and decrease in switched memory B cells (P = .022) were significant. When 24 patients are analyzed, cutaneous viral infections (n = 20), recurrent pneumonia (n = 18), Epstein Barr virus-associated lymphoproliferation (n = 11), atopic dermatitis (n = 10), autoimmune cytopenia (n = 7), and lymphoma (n = 6) were frequent. Lymphopenia, CD4 lymphopenia, high IgG, IgA, and IgE were common laboratory characteristics.
CONCLUSIONS
The differential diagnosis with autosomal recessive hyper-IgE syndrome is crucial. Because, atopy and CD4 lymphopenia are common in both diseases. Immunoglobulins, antibacterial, and antiviral prophylaxis are the mainstays of treatment. Clinicians may use immunomodulatory therapies during inflammatory or autoimmune complications. However, more data are needed to recommend hematopoietic stem cell transplantation as a safe therapy.

Identifiants

pubmed: 34146746
pii: S2213-2198(21)00659-0
doi: 10.1016/j.jaip.2021.05.032
pii:
doi:

Substances chimiques

Intracellular Signaling Peptides and Proteins 0
Threonine 2ZD004190S
Serine 452VLY9402
STK4 protein, human EC 2.7.1.11
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

3752-3766.e4

Informations de copyright

Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Auteurs

Deniz Cagdas (D)

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey; Department of Pediatric Immunology, Institute of Child Health, Hacettepe University Medical School, Ankara, Turkey. Electronic address: deniz.ayvaz@hacettepe.edu.tr.

Sevil Oskay Halacli (SO)

Department of Pediatric Immunology, Institute of Child Health, Hacettepe University Medical School, Ankara, Turkey.

Cagman Tan (C)

Department of Pediatric Immunology, Institute of Child Health, Hacettepe University Medical School, Ankara, Turkey.

Saliha Esenboga (S)

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey.

Betül Karaatmaca (B)

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey.

Pınar Gur Cetinkaya (PG)

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey.

Burcu Balcı-Hayta (B)

Department of Medical Biology, Hacettepe University Medical School, Ankara, Turkey.

Arzu Ayhan (A)

Department of Pediatric Pathology, Hacettepe University Medical School, Ankara, Turkey.

Aysegul Uner (A)

Department of Pediatric Pathology, Hacettepe University Medical School, Ankara, Turkey.

Diclehan Orhan (D)

Department of Pediatric Pathology, Hacettepe University Medical School, Ankara, Turkey.

Kaan Boztug (K)

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Seza Ozen (S)

Department of Pediatric Rheumatology, Hacettepe University Medical School, Ankara, Turkey.

Rezan Topaloglu (R)

Department of Pediatric Nephrology, Hacettepe University Medical School, Ankara, Turkey.

Ozden Sanal (O)

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey; Department of Pediatric Immunology, Institute of Child Health, Hacettepe University Medical School, Ankara, Turkey.

Ilhan Tezcan (I)

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey; Department of Pediatric Immunology, Institute of Child Health, Hacettepe University Medical School, Ankara, Turkey.

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