Frontiers in Immunology (Nov 2021)

Clinical and Immunological Features of Human BCL10 Deficiency

  • Blanca Garcia-Solis,
  • Blanca Garcia-Solis,
  • Blanca Garcia-Solis,
  • Ana Van Den Rym,
  • Ana Van Den Rym,
  • Ana Van Den Rym,
  • Jareb J. Pérez-Caraballo,
  • Jareb J. Pérez-Caraballo,
  • Abdulwahab Al–Ayoubi,
  • Anas M. Alazami,
  • Lazaro Lorenzo,
  • Carolina Cubillos-Zapata,
  • Carolina Cubillos-Zapata,
  • Eduardo López-Collazo,
  • Antonio Pérez-Martínez,
  • Antonio Pérez-Martínez,
  • Luis M. Allende,
  • Janet Markle,
  • Janet Markle,
  • Miguel Fernández-Arquero,
  • Miguel Fernández-Arquero,
  • Silvia Sánchez-Ramón,
  • Silvia Sánchez-Ramón,
  • Maria J. Recio,
  • Maria J. Recio,
  • Jean-Laurent Casanova,
  • Jean-Laurent Casanova,
  • Jean-Laurent Casanova,
  • Jean-Laurent Casanova,
  • Reem Mohammed,
  • Reem Mohammed,
  • Rubén Martinez-Barricarte,
  • Rubén Martinez-Barricarte,
  • Rebeca Pérez de Diego,
  • Rebeca Pérez de Diego,
  • Rebeca Pérez de Diego

DOI
https://doi.org/10.3389/fimmu.2021.786572
Journal volume & issue
Vol. 12

Abstract

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The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and TFH cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.

Keywords