Journal ArticleDOI
[Multiple facets of ADA2 deficiency: Vasculitis, auto-inflammatory disease and immunodeficiency: A literature review of 135 cases from literature].
Antoine Fayand,Guillaume Sarrabay,Alexandre Belot,Véronique Hentgen,Isabelle Koné-Paut,Gilles Grateau,Isabelle Melki,Sophie Georgin-Lavialle +7 more
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TLDR
The role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding as mentioned in this paper.Abstract:
Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding.read more
Citations
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Journal ArticleDOI
Autoinflammatory diseases: State of the art.
Sophie Georgin-Lavialle,Sophie Georgin-Lavialle,Antoine Fayand,François Rodrigues,Claude Bachmeyer,Léa Savey,Gilles Grateau +6 more
TL;DR: To better explore AID, some key anamnesis features are crucial such as the family tree, the age at onset, crisis length and organs involved in the clinical symptoms and an acute phase response is mandatory in crisis.
Journal ArticleDOI
Association of Vasculitis and Familial Mediterranean Fever
TL;DR: FMF, particularly when supported by two pathogenic MEFV mutations, could predispose to IgA vasculitis, or a PAN-like vasculopathy with more perirenal bleeding and CNS involvement.
Journal ArticleDOI
TNF inhibition in vasculitis management in adenosine deaminase 2 deficiency (DADA2)
TL;DR: In this paper , the authors performed Sanger sequencing of the ADA2 gene and used flow cytometry, intracellular cytokine staining, transcriptome analysis, immunohistochemistry, and cell differentiation experiments to define an inflammatory signature in patients with DADA2 and studied their response to TNF-inhibitor treatment.
Journal ArticleDOI
Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review
Sara Ganhão,Graça Barros Loureiro,Diana Rita Oliveira,Rúben Dos-Reis-Maia,Francisca Aguiar,Rita Quental,Carla Pinto Moura,João Luís Barreira,Mariana Rodrigues,Iva Brito +9 more
TL;DR: Doctors must be aware of this monogenic disorder, especially in the case of early-onset PAN-like manifestations, having a family member with similar manifestations or having consanguineous parents suggesting an autosomal recessive inheritance pattern, due to its excellent cost-effective results.
References
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Journal ArticleDOI
Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2
Qing Zhou,Dan Yang,Amanda K. Ombrello,Andrey Zavialov,Camilo Toro,Anton V. Zavialov,Deborah L. Stone,Jae Jin Chae,Sergio D. Rosenzweig,Kevin Bishop,Karyl S. Barron,Hye Sun Kuehn,Patrycja Hoffmann,Alejandra Negro,Wanxia L. Tsai,Edward W. Cowen,Wuhong Pei,Joshua D. Milner,Christopher Silvin,Theo Heller,David T. Chin,Nicholas J. Patronas,John S. Barber,Chyi-Chia Richard Lee,Geryl Wood,Alexander Ling,Susan J. Kelly,David E. Kleiner,James C. Mullikin,Nancy J. Ganson,Heidi H. Kong,Sophie Hambleton,Fabio Candotti,Martha Quezado,Katherine R. Calvo,Hawwa Alao,Beverly K. Barham,Anne Jones,James F. Meschia,Bradford B. Worrall,Scott E. Kasner,Stephen S. Rich,Raphaela Goldbach-Mansky,Mario Abinun,Elizabeth Chalom,Alisa Gotte,Marilynn Punaro,Virginia Pascual,James W. Verbsky,Troy R. Torgerson,Nora G. Singer,Timothy R. Gershon,Seza Ozen,Omer Karadag,Thomas A. Fleisher,Elaine F. Remmers,Shawn M. Burgess,Susan Moir,Massimo Gadina,Raman Sood,Michael S. Hershfield,Manfred Boehm,Daniel L. Kastner,Ivona Aksentijevich +63 more
TL;DR: Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis, and were prevented by coinjection with nonmutated (but not with mutated) human C ECR1.
Journal ArticleDOI
Mutant Adenosine Deaminase 2 in a Polyarteritis Nodosa Vasculopathy
Paulina Navon Elkan,Sarah B. Pierce,Reeval Segel,Reeval Segel,Tom Walsh,Judith Barash,Shai Padeh,Abraham Zlotogorski,Yackov Berkun,Joseph J. Press,Mukamel M,Isabel Voth,Philip J. Hashkes,Liora Harel,Vered Hoffer,Eduard Ling,Fatoş Yalçınkaya,Ozgur Kasapcopur,Ming K. Lee,Rachel E. Klevit,Paul Renbaum,Ariella Weinberg-Shukron,Ariella Weinberg-Shukron,Elif Funda Sener,Elif Funda Sener,Barbara Schormair,Sharon Zeligson,Dina Marek-Yagel,Tim M. Strom,Mordechai Shohat,Mordechai Shohat,Amihood Singer,Alan Rubinow,Elon Pras,Juliane Winkelmann,Juliane Winkelmann,Mustafa Tekin,Yair Anikster,Mary Claire King,Ephrat Levy-Lahad,Ephrat Levy-Lahad +40 more
TL;DR: Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression.
Journal ArticleDOI
Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review.
TL;DR: In this article, the authors reviewed the available scientific evidence, because patients frequently ask for dietary advice, and exclusive pharmacological treatment of RA is often not satisfying, and they suggested that fasting followed by vegetarian diet may help patients with rheumatoid arthritis.
Journal ArticleDOI
Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages.
Andrey V. Zavialov,Andrey V. Zavialov,Eduard Gracia,Nicolas Glaichenhaus,Rafael Franco,Anton V. Zavialov,Grégoire Lauvau +6 more
TL;DR: The discovery of the growth factor‐like activity of ADA2 explains clinical observations and suggests that this enzyme could be used as a drug candidate to modulate the immune responses during inflammation and cancer.
Journal ArticleDOI
ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study.
Roberta Caorsi,Federica Penco,Alice Grossi,Antonella Insalaco,Alessia Omenetti,Maria Alessio,Giovanni Conti,Federico Marchetti,Paolo Picco,Alberto Tommasini,Silvana Martino,Clara Malattia,Romina Gallizi,Rosa A. Podda,Annalisa Salis,Fernanda Falcini,Francesca Schena,Francesca Garbarino,Alessia Morreale,M Pardeo,Claudia Ventrici,Chiara Passarelli,Qing Zhou,Mariasavina Severino,Carlo Gandolfo,Gianluca Damonte,Alberto Martini,Angelo Ravelli,Ivona Aksentijevich,Isabella Ceccherini,Marco Gattorno +30 more
TL;DR: DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist and should complement genetic testing in patients with non-confirming genotypes.
Related Papers (3)
Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2
Qing Zhou,Dan Yang,Amanda K. Ombrello,Andrey Zavialov,Camilo Toro,Anton V. Zavialov,Deborah L. Stone,Jae Jin Chae,Sergio D. Rosenzweig,Kevin Bishop,Karyl S. Barron,Hye Sun Kuehn,Patrycja Hoffmann,Alejandra Negro,Wanxia L. Tsai,Edward W. Cowen,Wuhong Pei,Joshua D. Milner,Christopher Silvin,Theo Heller,David T. Chin,Nicholas J. Patronas,John S. Barber,Chyi-Chia Richard Lee,Geryl Wood,Alexander Ling,Susan J. Kelly,David E. Kleiner,James C. Mullikin,Nancy J. Ganson,Heidi H. Kong,Sophie Hambleton,Fabio Candotti,Martha Quezado,Katherine R. Calvo,Hawwa Alao,Beverly K. Barham,Anne Jones,James F. Meschia,Bradford B. Worrall,Scott E. Kasner,Stephen S. Rich,Raphaela Goldbach-Mansky,Mario Abinun,Elizabeth Chalom,Alisa Gotte,Marilynn Punaro,Virginia Pascual,James W. Verbsky,Troy R. Torgerson,Nora G. Singer,Timothy R. Gershon,Seza Ozen,Omer Karadag,Thomas A. Fleisher,Elaine F. Remmers,Shawn M. Burgess,Susan Moir,Massimo Gadina,Raman Sood,Michael S. Hershfield,Manfred Boehm,Daniel L. Kastner,Ivona Aksentijevich +63 more
Mutant Adenosine Deaminase 2 in a Polyarteritis Nodosa Vasculopathy
Paulina Navon Elkan,Sarah B. Pierce,Reeval Segel,Reeval Segel,Tom Walsh,Judith Barash,Shai Padeh,Abraham Zlotogorski,Yackov Berkun,Joseph J. Press,Mukamel M,Isabel Voth,Philip J. Hashkes,Liora Harel,Vered Hoffer,Eduard Ling,Fatoş Yalçınkaya,Ozgur Kasapcopur,Ming K. Lee,Rachel E. Klevit,Paul Renbaum,Ariella Weinberg-Shukron,Ariella Weinberg-Shukron,Elif Funda Sener,Elif Funda Sener,Barbara Schormair,Sharon Zeligson,Dina Marek-Yagel,Tim M. Strom,Mordechai Shohat,Mordechai Shohat,Amihood Singer,Alan Rubinow,Elon Pras,Juliane Winkelmann,Juliane Winkelmann,Mustafa Tekin,Yair Anikster,Mary Claire King,Ephrat Levy-Lahad,Ephrat Levy-Lahad +40 more
ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study.
Roberta Caorsi,Federica Penco,Alice Grossi,Antonella Insalaco,Alessia Omenetti,Maria Alessio,Giovanni Conti,Federico Marchetti,Paolo Picco,Alberto Tommasini,Silvana Martino,Clara Malattia,Romina Gallizi,Rosa A. Podda,Annalisa Salis,Fernanda Falcini,Francesca Schena,Francesca Garbarino,Alessia Morreale,M Pardeo,Claudia Ventrici,Chiara Passarelli,Qing Zhou,Mariasavina Severino,Carlo Gandolfo,Gianluca Damonte,Alberto Martini,Angelo Ravelli,Ivona Aksentijevich,Isabella Ceccherini,Marco Gattorno +30 more