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01-04-2022 | Stem Cell Transplantation | Original Article

Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency

Authors: Asena Pinar Sefer, Hassan Abolhassani, Franziska Ober, Basak Kayaoglu, Sevgi Bilgic Eltan, Altan Kara, Baran Erman, Naz Surucu Yilmaz, Cigdem Aydogmus, Sezin Aydemir, Louis-Marie Charbonnier, Burcu Kolukisa, Gholamreza Azizi, Samaneh Delavari, Tooba Momen, Simuzar Aliyeva, Yasemin Kendir Demirkol, Saban Tekin, Ayca Kiykim, Omer Faruk Baser, Haluk Cokugras, Mayda Gursel, Elif Karakoc-Aydiner, Ahmet Ozen, Daniel Krappmann, Talal A. Chatila, Nima Rezaei, Safa Baris

Published in: Journal of Clinical Immunology | Issue 3/2022

Abstract

Purpose

MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency.

Methods

The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation.

Results

The mean age of patients and disease onset were 33 ± 17 and 1.6 ± 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03).

Conclusion

This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life.

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Title: Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency
Authors: Asena Pinar Sefer
Hassan Abolhassani
Franziska Ober
Basak Kayaoglu
Sevgi Bilgic Eltan
Altan Kara
Baran Erman
Naz Surucu Yilmaz
Cigdem Aydogmus
Sezin Aydemir
Louis-Marie Charbonnier
Burcu Kolukisa
Gholamreza Azizi
Samaneh Delavari
Tooba Momen
Simuzar Aliyeva
Yasemin Kendir Demirkol
Saban Tekin
Ayca Kiykim
Omer Faruk Baser
Haluk Cokugras
Mayda Gursel
Elif Karakoc-Aydiner
Ahmet Ozen
Daniel Krappmann
Talal A. Chatila
Nima Rezaei
Safa Baris
Publication date: 01-04-2022
Publisher: Springer US
Keywords: Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Published in: Journal of Clinical Immunology / Issue 3/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-021-01191-4

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Purpose

Methods

Results

Conclusion

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