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Immunological Aspects of Kabuki Syndrome: A Retrospective Multicenter Study of the Italian Primary Immunodeficiency Network (IPINet)

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Abstract

Kabuki Syndrome (KS) is a multisystemic genetic disorder. A portion of patients has immunological manifestations characterized by increased susceptibility to infections and autoimmunity. Aiming to describe the clinical and laboratory immunological aspects of KS, we conducted a retrospective multicenter observational study on patients with KS treated in centers affiliated to the Italian Primary Immunodeficiency Network.

Thirty-nine patients were enrolled, with a median age at evaluation of 10 years (range: 3 m–21y). All individuals had organ malformations of variable severity. Congenital heart defect (CHD) was present in 19/39 patients (49%) and required surgical correction in 9/39 (23%), with associated thymectomy in 7/39 (18%). Autoimmune cytopenia occurred in 6/39 patients (15%) and was significantly correlated with thymectomy (p < 0.002), but not CHD. Individuals with cytopenia treated with mycophenolate as long-term immunomodulatory treatment (n = 4) showed complete response. Increased susceptibility to infections was observed in 22/32 patients (69%). IgG, IgA, and IgM were low in 13/29 (45%), 13/30 (43%) and 4/29 (14%) patients, respectively. Immunoglobulin substitution was required in three patients. Lymphocyte subsets were normal in all patients except for reduced naïve T-cells in 3/15 patients (20%) and reduced memory switched B-cells in 3/17 patients (18%). Elevated CD3 + TCRαβ + CD4-CD8-T-cells were present in 5/17 individuals (23%) and were correlated with hematological and overall autoimmunity (p < 0.05).

In conclusion, immunological manifestations of KS in our cohort include susceptibility to infections, antibody deficiency, and autoimmunity. Autoimmune cytopenia is correlated with thymectomy and elevated CD3 + TCRαβ + CD4-CD8-T-cells, and benefits from treatment with mycophenolate.

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Data Availability

The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Fondazione Città della Speranza ONLUS (http://cittadellasperanza.org), Associazione di Promozione Sociale “Genitori in fuga” (https://www.genitoriinfuga.org) for their support to our scientific work. We would like to thank the patients, the patients’ families, and the nurses for their collaboration and efforts.

Author information

Authors and Affiliations

  1. Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, Via Giustiniani 3, Padua, 35128, Italy

    Linda Rossini, Elisa Carraro, Alessandra Biffi, Maria Caterina Putti & Antonio Marzollo

  2. Maternal and Child Health Department, Padua University, Via Giustiniani, 3, Padua, 35128, Italy

    Linda Rossini & Alessandra Biffi

  3. Immunology, Pediatric Unit, IRCCS Meyer Children’s Hospital, viale G.Pieraccini 24, Florence, 50139, Italy

    Silvia Ricci & Chiara Azzari

  4. Department of Health Sciences, University of Florence, Florence, Italy

    Silvia Ricci, Chiara Azzari & Stefano Stagi

  5. Immunology and Rheumatology Unit, Regina Margherita Children Hospital, Turin, Italy

    Davide Montin

  6. Centre of Excellence, Department of Pediatric Hematology-Oncology, IRCCS Meyer Children’s Hospital, Florence, Italy

    Eleonora Gambineri & Marco Tellini

  7. Department of “NEUROFARBA”, Section of Child’s Health, University of Florence, Florence, Italy

    Eleonora Gambineri

  8. Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, 40138, Italy

    Francesca Conti & Andrea Pession

  9. Dept. of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy

    Francesca Conti & Andrea Pession

  10. Tettamanti Research Center, University of Milano-Bicocca, University of Milano Bicocca, Monza, Italy

    Francesco Saettini

  11. Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, Italy

    Samuele Naviglio, Erica Valencic & Andrea Magnolato

  12. Department of Pediatrics, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Lucia Baselli

  13. UOC Pediatria, San Bortolo Hospital, Vicenza, Italy

    Sara Azzolini

  14. Section of Clinical and Laboratory Immunology, Division of Pediatrics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Rita Consolini

  15. Maternal, Infantile and Urological Sciences Department, Sapienza University of Rome, Rome, Italy

    Lucia Leonardi

  16. Paediatric Haematology-Oncology, Maternal Infant Hospital “G. Salesi”, Ancona, Italy

    Irene D’Alba

  17. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy

    Roberta Romano, Emilia Cirillo, Giuliana Giardino & Claudio Pignata

  18. Department of Medicine, Surgery and Dentistry, University of Salerno, Via Salvador Allende Baronissi, Campania, 84081, Italy

    Daniela Melis

  19. Auxoendocrinology Division, Meyer Children’s Hospital, IRCCS, viale G.Pieraccini 24, Florence, 50139, Italy

    Stefano Stagi

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  1. Linda Rossini
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  2. Silvia Ricci
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  27. Antonio Marzollo
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Contributions

AMar and MCP conceived and designed the study on behalf of the IPINet. SR, DMo, CA, EG, MT, FC, AP, FS, SN, EV, AMag, LB, SA, RC, LL, IDA, RR, DMe, SS, ECi, GG, AB, CP, AMar collected the data and treated the patients. Data analysis was performed by LR, AMar and ECa. The manuscript was written by AMar and LR with contributions from all authors. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Antonio Marzollo.

Ethics declarations

Ethics Approval

The study was approved from the local hospital Ethical Committee and was conducted in accordance with the Helsinki Declaration.

Consent to Participate

Informed consent was collected from all patients or their legal guardians.

Consent for Publication

Informed consent was collected from all patients or their legal guardians.

Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Additional information

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

On behalf of the Italian Primary Immunodeficiency Network (IPINet).

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Rossini, L., Ricci, S., Montin, D. et al. Immunological Aspects of Kabuki Syndrome: A Retrospective Multicenter Study of the Italian Primary Immunodeficiency Network (IPINet). J Clin Immunol 44, 105 (2024). https://doi.org/10.1007/s10875-024-01676-y

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