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Delayed Diagnosis of Chronic Necrotizing Granulomatous Skin Lesions due to TAP2 Deficiency

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Abstract

Major histocompatibility complex class I (MHC-I) deficiency, also known as bare lymphocyte syndrome type 1 (BLS-1), is a rare autosomal recessively inherited immunodeficiency disorder with remarkable clinical and biological heterogeneity. Transporter associated with antigen processing (TAP) is a member of the ATP-binding cassette superfamily of transporters and consists of two subunits, TAP1 or TAP2. Any defect resulting from a mutation or deletion of these two subunits may adversely affect the peptide translocation in the endoplasmic reticulum, which is an important process for properly assembling MHC-I molecules. To date, only 12 TAP2-deficient patients were reported in the literature. Herein, we described two Iranian cases with 2 and 3 decades of delayed diagnosis of chronic necrotizing granulomatous skin lesions due to TAP2 deficiency without pulmonary involvement. Segregation analysis in family members identified 3 additional homozygous asymptomatic carriers. In both asymptomatic and symptomatic carriers, HLA-I expression was only 4–15% of the one observed in healthy controls. We performed the first deep immunophenotyping in TAP2-deficient patients. While total CD8 T cell counts were normal as previously reported, the patients showed strongly impaired naïve CD8 T cell counts. Mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cell counts were increased.

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Acknowledgements

The authors would like to thank the patients and Clinical Research Development Unit (CRDU) of Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, for their help and support in conducting this study.

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Authors and Affiliations

  1. Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 193955487, Tehran, Iran

    Ilad Alavi Darazam, Atousa Hakamifard, Farid Javandoust Gharehbagh & Firouze Hatami

  2. Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, P.O. Box 193955487, Tehran, Iran

    Ilad Alavi Darazam

  3. Department of Infectious Diseases, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Atousa Hakamifard

  4. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR-1163, Necker Hospital for Sick Children, Paris, France

    Mana Momenilandi, Marie Materna, Antoine Fayand, Jean-Laurent Casanova & Vivien Béziat

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

    Mana Momenilandi, Marie Materna, Antoine Fayand, Jean-Laurent Casanova & Vivien Béziat

  6. Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran

    Mohammad Shahrooei, Nasrin Alipour Olyaei & Jean-Laurent Casanova

  7. Genomic Research Center and Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Shahrooei & Nasrin Alipour Olyaei

  8. Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Farahnaz Bidari Zerehpoosh

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

    Antoine Fayand & Vivien Béziat

  10. Internal Medicine Department, French National Reference Center for Autoinflammatory Diseases (CEREMAIA), Tenon Hospital, Sorbonne University, Paris, France

    Antoine Fayand & Jean-Laurent Casanova

  11. Department of Nephrology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Legha Lotfollahi

  12. Division of Pulmonary Medicine, Department of Medicine, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland

    Nahal Mansouri

  13. Howard Hughes Medical Institute, New York, NY, USA

    Jean-Laurent Casanova

  14. Department of Pediatrics, Necker Hospital for Sick Children, Paris, France

    Jean-Laurent Casanova

  15. Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Davood Mansouri

  16. Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Davood Mansouri

Authors
  1. Ilad Alavi Darazam
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  2. Atousa Hakamifard
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  3. Mana Momenilandi
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  4. Marie Materna
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  5. Farid Javandoust Gharehbagh
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  6. Mohammad Shahrooei
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  7. Nasrin Alipour Olyaei
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  8. Farahnaz Bidari Zerehpoosh
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  9. Antoine Fayand
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  10. Firouze Hatami
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  11. Legha Lotfollahi
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  12. Nahal Mansouri
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  13. Jean-Laurent Casanova
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  14. Vivien Béziat
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  15. Davood Mansouri
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by IAD, DM, VB, and JLC. The first draft of the manuscript was written by AH and IAD, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ilad Alavi Darazam.

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Ethics Approval

This research was approved by the ethics committee of Shahid Beheshti University of Medical Sciences (ethical code: IR.SBMU.RETECH.REC.1400.1021).

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All participants signed the informed consent for the immunological study and provided consent for the publication of data.

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The authors declare no competing interests.

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Darazam, I.A., Hakamifard, A., Momenilandi, M. et al. Delayed Diagnosis of Chronic Necrotizing Granulomatous Skin Lesions due to TAP2 Deficiency. J Clin Immunol 43, 217–228 (2023). https://doi.org/10.1007/s10875-022-01374-7

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  • DOI: https://doi.org/10.1007/s10875-022-01374-7

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