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Hematopoietic Stem Cell Transplantation in ARPC1B Deficiency


Mutations in the ARPC1B isoform component of human actin-related protein 2/3 complex have been recently associated with an inborn error of immunity characterized by combined immunodeficiency, allergies, autoinflammation, and platelet abnormalities. Currently, indications on the management of this novel disease and information on its outcome are lacking. We report the first case series of 7 children with a homozygous mutation in ARPC1B gene who underwent allogeneic-HSCT (allo-HSCT). All patients presented an early clinical onset, characterized by recurrent infections, failure to thrive and gastrointestinal bleeding episodes complicated with neonatal hemorrhagic enteritis in 3 cases, and macrophage activating syndrome in 2. Allo-HSCT was performed at the median age of 1.83 years after a myeloablative conditioning regimen in all cases. Engraftment occurred in all patients with full donor chimerism in 6 out of 7. The clinical course after engraftment was uneventful in 3 out of 7 children; 2 patients developed a grade 1–2 acute graft-versus-host disease (GvHD), and 1 patient a grade 1 chronic-GvHD. JC virus-related progressive multifocal leukoencephalopathy was diagnosed in one patient 13 months after haploidentical-HSCT and successfully managed with donor-derived viral-specific T-cell infusion. Only one patient had a fatal outcome 3 months after HSCT because of sepsis, after veno-occlusive disease, and transplant-associated microangiopathy. At a median follow-up of 19 months (range 3–110), 6 out of 7 patients are alive and disease-free. The severity of the clinical phenotype at diagnosis and the high survival rate, with limited transplant-related morbidity, strongly support the indication to allo-HSCT for patients with this diagnosis.

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Authors and Affiliations



SG, SV, MF, and MG contributed to the study conception and design. All other authors contributed to the clinical management and data collection, each for patients belonging to their own center. Material preparation, data collection, and analysis were performed by SG and FL. The first draft of the manuscript was written by SG. All authors contributed to manuscript revision and approved its final version.

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

Corresponding author

Correspondence to Stefano Giardino.

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This study, performed in line with the principles of the Declaration of Helsinki, is an observational retrospective study that collects pseudo-anonymized data. The Research Ethics Committee of each Centre involved has confirmed that no ethical approval is required.

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Informed consent to participate in retrospective study was obtained from the parents of all individual participants included in the study.

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The authors declare no competing interests.

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Giardino, S., Volpi, S., Lucioni, F. et al. Hematopoietic Stem Cell Transplantation in ARPC1B Deficiency. J Clin Immunol (2022).

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  • ARPC1B deficiency
  • Allogenic-HSCT
  • Primary immunodeficiency
  • Autoinflammatory disease