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SCID and Other Inborn Errors of Immunity with Low TRECs — the Brazilian Experience

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Abstract

Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infections due to absent or non-functional T cells. Without early diagnosis and curative treatment, most die in early infancy. As most affected infants appear healthy at birth, newborn screening (NBS) is essential to identify and treat patients before the onset of symptoms. Here, we report 47 Brazilian patients investigated between 2009 and 2020 for SCID due to either a positive family history and/or clinical impression and low TRECs. Based on clinical presentation, laboratory finding, and genetic information, 24 patients were diagnosed as typical SCID, 14 as leaky SCID, and 6 as Omenn syndrome; 2 patients had non-SCID IEI, and 1 remained undefined. Disease onset median age was 2 months, but at the time of diagnosis and treatment, median ages were 6.5 and 11.5 months, respectively, revealing considerable delay which affected negatively treatment success. While overall survival was 51.1%, only 66.7% (30/45) lived long enough to undergo hematopoietic stem-cell transplantation, which was successful in 70% of cases. Forty-three of 47 (91.5%) patients underwent genetic testing, with a 65.1% success rate. Even though our patients did not come from the NBS programs, the diagnosis of SCID improved in Brazil during the pilot programs, likely due to improved medical education. However, we estimate that at least 80% of SCID cases are still missed. NBS-SCID started to be universally implemented in the city of São Paulo in May 2021, and it is our hope that other cities will follow, leading to early diagnosis and higher survival of SCID patients in Brazil.

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Data Availability

The data generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank the patients, their families, and all healthcare professionals that made this study possible. We specially acknowledge the support of the Jeffrey Modell Foundation, which was instrumental to the development of this work. We thank Dr Jean Laurent Casanova’s group for genetic annotation assistance, Dr. Peter Newburger for information about the VPS45 variant, Dr Juliana F Fernandes for patient transplantation information, and Dr. Gustavo B Ferreira for statistical support. Lastly, we would like to acknowledge the relevance of the work of Dr. Beatriz Tavares Costa-Carvalho (in memorian) for the present work and for patients suffering of inborn errors of immunity.

Funding

Jeffrey Modell Foundation (LAB and ACN), Fundação de Amparo à Pesquisa do Estado de São Paulo — FAPESP (grants 2016/22158–3 for ACN and 2018/09407–0 for LAB), Centro Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301299/2018–8—ACN), Brazilian Ministry of Health grant PRONAS/PDC (25000.077928/2015–06—ACN and LAB), Investigator-Initiated Research grant from Takeda Pharma Ltda (no. IISR-2020–103243—ACN), Robert A. Good Endowment, University of South Florida (JEW).

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Authors and Affiliations

  1. Laboratory of Human Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730, Av. Professor Lineu Prestes, Sao Paulo, SP, 05508-000, Brazil

    Lucila Akune Barreiros, Jusley Lira Sousa, Marilia Pylles Patto Kanegae, Tábata Takahashi França & Antonio Condino-Neto

  2. Immunology Outpatient Clinic, Vienna, Austria

    Christoph Geier & Alexander Leiss-Piller

  3. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA

    Bertrand Boisson & Jacinta Bustamante

  4. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France

    Bertrand Boisson & Jacinta Bustamante

  5. Imagine Institute, University of Paris, Paris, France

    Bertrand Boisson & Jacinta Bustamante

  6. Sabará Hospital, PENSI Institute - Jose Luiz Egydio Setubal Foundation, Sao Paulo, SP, Brazil

    Alessandra Miramontes Lima & Fátima Rodrigues Fernandes

  7. Universidade Federal de São Paulo, Sao Paulo, SP, Brazil

    Beatriz Tavares Costa-Carvalho, Carolina Sanchez Aranda & Maria Isabel de Moraes-Pinto

  8. Departamento de Pediatra, Universidade Federal de Uberlândia, Uberlandia, MG, Brazil

    Gesmar Rodrigues Silva Segundo

  9. Hospital Infantil Albert Sabin, Fortaleza, CE, Brazil

    Janaira Fernandes Severo Ferreira

  10. Hospital da Criança de Brasília José de Alencar, Brasilia, DF, Brazil

    Fabíola Scancetti Tavares

  11. Hospital Materno Infantil de Brasília, Brasilia, DF, Brazil

    Flávia Alice Timburiba de Medeiros Guimarães

  12. Faculdade de Medicina de São José Do Rio Preto, Sao Jose Do Rio Preto, SP, Brazil

    Eliana Cristina Toledo

  13. Departamento de Pediatria E Imunologia, Hospital Universitário de Taubaté, Universidade de Taubaté, Taubate, SP, Brazil

    Ana Carolina da Matta Ain

  14. Hospital Universitário Prof. Alberto Antunes, Maceio, AL, Brazil

    Iramirton Figueirêdo Moreira

  15. Hospital das Clínicas, Universidade Federal de Santa Caratina, Florianopolis, SC, Brazil

    Gustavo Soldatelli

  16. Faculdade de Medicina, Centro Universitário FMABC, Santo Andre, SP, Brazil

    Anete Sevciovic Grumach

  17. Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, SP, Brazil

    Mayra de Barros Dorna

  18. Hospital das Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Cristina Worm Weber

  19. Hospital da Criança Conceição, Porto Alegre, RS, Brazil

    Regina Sumiko Watanabe Di Gesu

  20. Departamento de Pediatria, Universidade Federal Do Rio Grande Do Norte, Natal, RN, Brazil

    Vera Maria Dantas

  21. Allen Institute for Immunology, Seattle, USA

    Troy Robert Torgerson

  22. Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Research Institute, Seattle, USA

    Hans Dietrich Ochs

  23. Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France

    Jacinta Bustamante

  24. University of South Florida at Johns Hopkins All Children’s Hospital, Saint Petersburg, FL, USA

    Jolan Eszter Walter

  25. Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA, USA

    Jolan Eszter Walter

  26. Immunogenic Laboratories Inc, Sao Paulo, SP, Brazil

    Antonio Condino-Neto

Authors
  1. Lucila Akune Barreiros
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  2. Jusley Lira Sousa
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  3. Christoph Geier
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  8. Alessandra Miramontes Lima
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  9. Beatriz Tavares Costa-Carvalho
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  11. Maria Isabel de Moraes-Pinto
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  14. Fabíola Scancetti Tavares
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  15. Flávia Alice Timburiba de Medeiros Guimarães
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  17. Ana Carolina da Matta Ain
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  18. Iramirton Figueirêdo Moreira
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  20. Anete Sevciovic Grumach
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  29. Jolan Eszter Walter
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  30. Antonio Condino-Neto
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Contributions

Lucila Akune Barreiros, Marilia Pylles Patto Kanegae, and Antonio Condino-Neto contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Lucila Akune Barreiros, Jusley Lira Sousa, Christoph Geier, Alexander Leiss-Piller, Marilia Pylles Patto Kanegae, and Tábata Takahashi França. The first draft of the manuscript was written by Lucila Akune Barreiros, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Antonio Condino-Neto.

Ethics declarations

Ethics Approval

This study was approved by the ethics committee of the Institute of Biomedical Sciences of the University of São Paulo (CAAE 54324416.5.000.5467).

Consent to Participate and Consent to Publish

Informed consent was given by either parent or another family member to allow for sample collection and data publication of all patients.

Competing Interests

The authors declare no competing interests.

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Dedicated to Beatriz Tavares Costa-Carvalho, who passed away during the presentation of this study.

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Barreiros, L.A., Sousa, J.L., Geier, C. et al. SCID and Other Inborn Errors of Immunity with Low TRECs — the Brazilian Experience. J Clin Immunol 42, 1171–1192 (2022). https://doi.org/10.1007/s10875-022-01275-9

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  • DOI: https://doi.org/10.1007/s10875-022-01275-9

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