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

Date

2022-01-01

Author

Sefer, Asena Pinar
Abolhassani, Hassan
Ober, Franziska
Kayaoğlu, Başak
Eltan, Sevgi Bilgic
Kara, Altan
ERMAN, BARAN
Yilmaz, Naz Surucu
Aydogmus, Cigdem
Aydemir, Sezin
Charbonnier, Louis-Marie
KOLUKISA, BURCU
Azizi, Gholamreza
Delavari, Samaneh
Momen, Tooba
Aliyeva, Simuzar
Demirkol, Yasemin Kendir
Tekin, Saban
KIYKIM, AYÇA
Baser, Omer Faruk
ÇOKUĞRAŞ, HALUK CEZMİ
Gürsel, Mayda
Karakoc-Aydiner, Elif
Ozen, Ahmet
Krappmann, Daniel
Chatila, Talal A.
Rezaei, Nima
BARIŞ, SAFA

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

286
views

0
downloads

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.

Subject Keywords

Inborn errors of immunity, primary immunodeficiency, MALT1, combined immune deficiency, immune dysregulation, recurrent infections, skin involvement, failure to thrive, hematopoietic stem cell transplantation, NF-KAPPA-B, T-CELL, COMBINED IMMUNODEFICIENCY, MUTATIONS, ACTIVATION, CARMA1, ROLES

URI

https://hdl.handle.net/11511/95416

Journal

JOURNAL OF CLINICAL IMMUNOLOGY

DOI

https://doi.org/10.1007/s10875-021-01191-4

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Evaluation of disseminated candidiasis on an experimental animal model: A Fourier transform infrared study Dogan, Ayca; Ergen, Kivanc; Budak, Fatma; Severcan, Feride (SAGE Publications, 2007-02-01) Invasive candidiasis, defined as candidemia and disseminated candidiasis, is the most common fungal infection in hospitalized patients. In the current study, we used Fourier transform infrared (FT-IR) spectroscopy as a rapid, non-perturbing technique to investigate the effects of disseminated candidiasis on mouse liver tissues at the molecular level. The results revealed that the infection caused compositional changes in the tissues by decreasing the lipid content and the ratio of the saturated lipids to un...
Assessment of the immunogenicity and formulation of recombinant proteins from SARS-CoV-2 as vaccine antigens Keser, Duygu; Özcengiz, Gülay; Department of Biology (2022-9-15) COVID-19 is an infectious disease caused by SARS-CoV-2. The virus was first detected in Wuhan, China in late 2019, and the outbreak was declared a pandemic in January 2020 by WHO, and continues to spread worldwide. As of July 2022, more than 575 million confirmed cases have been detected all over the world, and more than 6 million people died from the disease. One of the most important public health measures in combating the spread of infectious diseases is vaccination. Despite the existence of rapidly deve...
Recent developments in cell-based assays and stem cell technologies for botulinum neurotoxin research and drug discovery. Kiriş, Erkan; Burnett, JC; Soloveva, V; Kane, CD; Bavari, S (2014-03-01) Botulinum neurotoxins (BoNTs) are exceptionally potent inhibitors of neurotransmission, causing muscle paralysis and respiratory failure associated with the disease botulism. Currently, no drugs are available to counter intracellular BoNT poisoning. To develop effective medical treatments, cell-based assays provide a valuable system to identify novel inhibitors in a time- and costefficient manner. Consequently, cell-based systems including immortalized cells, primary neurons, and stem-cell derived neurons h...
Development of an experimental recombinant vaccine formulation composed of LKTA from Mannheimia Haemolytica A1 and P31 and LPPB from Histophilus Somni 8025 against Hovine Respiratory Disease Türkmen, Nazlı Hilal; Özcengiz, Gülay; Department of Molecular Biology and Genetics (2020-9) Two major bacterial pathogens of Bovine Respiratory Disease (BRD), Mannheimia haemolytica and Histophilus somni are Gram-negative, opportunistic bacteria that live in upper respiratory tracts of ruminants commensally. The one of the most important virulence factor of M. haemolytica, leukotoxin, is responsible for lung colonization and establishment of infection. On the other hand, H. somni OMPs have a significant contribution to the pathogenicity of the organism. As the disease results in a destroyed animal...
Improving the Computer-Aided Estimation of Ulcerative Colitis Severity According to Mayo Endoscopic Score by Using Regression-Based Deep Learning Polat, Gorkem; Kani, Haluk Tarik; Ergenc, Ilkay; Alahdab, Yesim Ozen; Temizel, Alptekin; Atug, Ozlen (2022-11-01) Background Assessment of endoscopic activity in ulcerative colitis (UC) is important for treatment decisions and monitoring disease progress. However, substantial inter- and intraobserver variability in grading impairs the assessment. Our aim was to develop a computer-aided diagnosis system using deep learning to reduce subjectivity and improve the reliability of the assessment. Methods The cohort comprises 11 276 images from 564 patients who underwent colonoscopy for UC. We propose a regression-based deep ...

Citation Formats

A. P. Sefer et al., “Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency,” JOURNAL OF CLINICAL IMMUNOLOGY, pp. 0–0, 2022, Accessed: 00, 2022. [Online]. Available: https://hdl.handle.net/11511/95416.