Cargando…

Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia

STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified...

Descripción completa

Detalles Bibliográficos
Autores principales: Ciullini Mannurita, Sara, Goda, Rayan, Schiavo, Ebe, Coniglio, Maria Luisa, Azzali, Annachiara, Fotzi, Ilaria, Tondo, Annalisa, Tintori, Veronica, Frenos, Stefano, Sanvito, Maria Chiara, Vignoli, Marina, Luceri, Cristina, Bigagli, Elisabetta, Grassi, Alessia, D’Elios, Mario Milco, Favre, Claudio, Gambineri, Eleonora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843414/
https://www.ncbi.nlm.nih.gov/pubmed/33519826
http://dx.doi.org/10.3389/fimmu.2020.620046
_version_ 1783644136321056768
author Ciullini Mannurita, Sara
Goda, Rayan
Schiavo, Ebe
Coniglio, Maria Luisa
Azzali, Annachiara
Fotzi, Ilaria
Tondo, Annalisa
Tintori, Veronica
Frenos, Stefano
Sanvito, Maria Chiara
Vignoli, Marina
Luceri, Cristina
Bigagli, Elisabetta
Grassi, Alessia
D’Elios, Mario Milco
Favre, Claudio
Gambineri, Eleonora
author_facet Ciullini Mannurita, Sara
Goda, Rayan
Schiavo, Ebe
Coniglio, Maria Luisa
Azzali, Annachiara
Fotzi, Ilaria
Tondo, Annalisa
Tintori, Veronica
Frenos, Stefano
Sanvito, Maria Chiara
Vignoli, Marina
Luceri, Cristina
Bigagli, Elisabetta
Grassi, Alessia
D’Elios, Mario Milco
Favre, Claudio
Gambineri, Eleonora
author_sort Ciullini Mannurita, Sara
collection PubMed
description STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.
format Online
Article
Text
id pubmed-7843414
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78434142021-01-30 Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia Ciullini Mannurita, Sara Goda, Rayan Schiavo, Ebe Coniglio, Maria Luisa Azzali, Annachiara Fotzi, Ilaria Tondo, Annalisa Tintori, Veronica Frenos, Stefano Sanvito, Maria Chiara Vignoli, Marina Luceri, Cristina Bigagli, Elisabetta Grassi, Alessia D’Elios, Mario Milco Favre, Claudio Gambineri, Eleonora Front Immunol Immunology STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention. Frontiers Media S.A. 2021-01-15 /pmc/articles/PMC7843414/ /pubmed/33519826 http://dx.doi.org/10.3389/fimmu.2020.620046 Text en Copyright © 2021 Ciullini Mannurita, Goda, Schiavo, Coniglio, Azzali, Fotzi, Tondo, Tintori, Frenos, Sanvito, Vignoli, Luceri, Bigagli, Grassi, D’Elios, Favre and Gambineri http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ciullini Mannurita, Sara
Goda, Rayan
Schiavo, Ebe
Coniglio, Maria Luisa
Azzali, Annachiara
Fotzi, Ilaria
Tondo, Annalisa
Tintori, Veronica
Frenos, Stefano
Sanvito, Maria Chiara
Vignoli, Marina
Luceri, Cristina
Bigagli, Elisabetta
Grassi, Alessia
D’Elios, Mario Milco
Favre, Claudio
Gambineri, Eleonora
Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia
title Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia
title_full Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia
title_fullStr Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia
title_full_unstemmed Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia
title_short Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia
title_sort case report: signal transducer and activator of transcription 3 gain-of-function and spectrin deficiency: a life-threatening case of severe hemolytic anemia
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843414/
https://www.ncbi.nlm.nih.gov/pubmed/33519826
http://dx.doi.org/10.3389/fimmu.2020.620046
work_keys_str_mv AT ciullinimannuritasara casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT godarayan casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT schiavoebe casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT conigliomarialuisa casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT azzaliannachiara casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT fotziilaria casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT tondoannalisa casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT tintoriveronica casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT frenosstefano casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT sanvitomariachiara casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT vignolimarina casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT lucericristina casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT bigaglielisabetta casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT grassialessia casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT deliosmariomilco casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT favreclaudio casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia
AT gambinerieleonora casereportsignaltransducerandactivatoroftranscription3gainoffunctionandspectrindeficiencyalifethreateningcaseofseverehemolyticanemia