Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient

<div><p>The scope of this study is to show that DM in a LRBA-deficient patient with a stop codon mutation (c.3999 G > A) was not mediated through autoimmunity. We have evaluated the ability of the proband’s T cells to be activated by assessing their CTLA-4 expression. A nonsignificant...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Iman Hawari (12561958) (author)
مؤلفون آخرون: Johan Ericsson (49714) (author), Basirudeen Syed Ahamed Kabeer (9676280) (author), Damien Chaussabel (26369) (author), Asma Alsulaiti (18281824) (author), Sanaa A. Sharari (18281827) (author), Cristina Maccalli (2632465) (author), Faiyaz Ahmad Khan (18281830) (author), Khalid Hussain (110443) (author)
منشور في: 2022
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author Iman Hawari (12561958)
author2 Johan Ericsson (49714)
Basirudeen Syed Ahamed Kabeer (9676280)
Damien Chaussabel (26369)
Asma Alsulaiti (18281824)
Sanaa A. Sharari (18281827)
Cristina Maccalli (2632465)
Faiyaz Ahmad Khan (18281830)
Khalid Hussain (110443)
author2_role author
author
author
author
author
author
author
author
author_facet Iman Hawari (12561958)
Johan Ericsson (49714)
Basirudeen Syed Ahamed Kabeer (9676280)
Damien Chaussabel (26369)
Asma Alsulaiti (18281824)
Sanaa A. Sharari (18281827)
Cristina Maccalli (2632465)
Faiyaz Ahmad Khan (18281830)
Khalid Hussain (110443)
author_role author
dc.creator.none.fl_str_mv Iman Hawari (12561958)
Johan Ericsson (49714)
Basirudeen Syed Ahamed Kabeer (9676280)
Damien Chaussabel (26369)
Asma Alsulaiti (18281824)
Sanaa A. Sharari (18281827)
Cristina Maccalli (2632465)
Faiyaz Ahmad Khan (18281830)
Khalid Hussain (110443)
dc.date.none.fl_str_mv 2022-04-18T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/biology11040612
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Understanding_the_Mechanism_of_Diabetes_Mellitus_in_a_LRBA-Deficient_Patient/25516195
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Agricultural, veterinary and food sciences
Agricultural biotechnology
Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Immunology
diabetes mellitus
autoimmunity
LRBA
CTLA-4
blood transcriptomics
insulin secretion
dc.title.none.fl_str_mv Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>The scope of this study is to show that DM in a LRBA-deficient patient with a stop codon mutation (c.3999 G > A) was not mediated through autoimmunity. We have evaluated the ability of the proband’s T cells to be activated by assessing their CTLA-4 expression. A nonsignificant difference was seen in the CTLA-4 expression on CD3+ T cells compared to the healthy control at basal level and after stimulation with PMA/ionomycin. Blood transcriptomic analysis have shown a remarkable increase in abundance of transcripts related to CD71+ erythroid cells. There were no differences in the expression of modules related to autoimmunity diseases between the proband and pooled healthy controls. In addition, our novel findings show that siRNA knockdown of LRBA in mouse pancreatic β-cells leads reduced cellular proinsulin, insulin and consequently insulin secretion, without change in cell viability in cultured MIN6 cells.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biology<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biology11040612" target="_blank">https://dx.doi.org/10.3390/biology11040612</a></p>
eu_rights_str_mv openAccess
id Manara2_2f786237eb9f3818587ad0362a053a5d
identifier_str_mv 10.3390/biology11040612
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25516195
publishDate 2022
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rights_invalid_str_mv CC BY 4.0
spelling Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient PatientIman Hawari (12561958)Johan Ericsson (49714)Basirudeen Syed Ahamed Kabeer (9676280)Damien Chaussabel (26369)Asma Alsulaiti (18281824)Sanaa A. Sharari (18281827)Cristina Maccalli (2632465)Faiyaz Ahmad Khan (18281830)Khalid Hussain (110443)Agricultural, veterinary and food sciencesAgricultural biotechnologyBiological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesImmunologydiabetes mellitusautoimmunityLRBACTLA-4blood transcriptomicsinsulin secretion<div><p>The scope of this study is to show that DM in a LRBA-deficient patient with a stop codon mutation (c.3999 G > A) was not mediated through autoimmunity. We have evaluated the ability of the proband’s T cells to be activated by assessing their CTLA-4 expression. A nonsignificant difference was seen in the CTLA-4 expression on CD3+ T cells compared to the healthy control at basal level and after stimulation with PMA/ionomycin. Blood transcriptomic analysis have shown a remarkable increase in abundance of transcripts related to CD71+ erythroid cells. There were no differences in the expression of modules related to autoimmunity diseases between the proband and pooled healthy controls. In addition, our novel findings show that siRNA knockdown of LRBA in mouse pancreatic β-cells leads reduced cellular proinsulin, insulin and consequently insulin secretion, without change in cell viability in cultured MIN6 cells.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biology<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biology11040612" target="_blank">https://dx.doi.org/10.3390/biology11040612</a></p>2022-04-18T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/biology11040612https://figshare.com/articles/journal_contribution/Understanding_the_Mechanism_of_Diabetes_Mellitus_in_a_LRBA-Deficient_Patient/25516195CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/255161952022-04-18T03:00:00Z
spellingShingle Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
Iman Hawari (12561958)
Agricultural, veterinary and food sciences
Agricultural biotechnology
Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Immunology
diabetes mellitus
autoimmunity
LRBA
CTLA-4
blood transcriptomics
insulin secretion
status_str publishedVersion
title Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
title_full Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
title_fullStr Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
title_full_unstemmed Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
title_short Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
title_sort Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
topic Agricultural, veterinary and food sciences
Agricultural biotechnology
Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Immunology
diabetes mellitus
autoimmunity
LRBA
CTLA-4
blood transcriptomics
insulin secretion