Prevalence of Immunological Defects in a Cohort of 97 Rubinstein–Taybi Syndrome Patients

Abstract

Although recurrent infections in Rubinstein–Taybi syndrome (RSTS) are common, and probably multifactorial, immunological abnormalities have not been extensively described with only isolated cases or small case series of immune deficiency and dysregulation having been reported. The objective of this study was to investigate primary immunodeficiency (PID) and immune dysregulation in an international cohort of patients with RSTS. All published cases of RSTS were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Ninety-seven RSTS patients were identified. For 45 patients, we retrieved data from the published reports while for 52 patients, a clinical update was provided. Recurrent or severe infections, autoimmune/autoinflammatory complications, and lymphoproliferation were observed in 72.1%, 12.3%, and 8.2% of patients. Syndromic immunodeficiency was diagnosed in 46.4% of individuals. Despite the broad heterogeneity of immunodeficiency disorders, antibody defects were observed in 11.3% of subjects. In particular, these patients presented hypogammaglobulinemia associated with low B cell counts and reduction of switched memory B cell numbers. Immunoglobulin replacement therapy, antibiotic prophylaxis, and immunosuppressive treatment were employed in 16.4%, 8.2%, and 9.8% of patients, respectively. Manifestations of immune dysfunctions, affecting mostly B cells, are more common than previously recognized in patients with RSTS. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment.

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Abbreviations

ALPS:

Autoimmune lymphoproliferative syndrome

CID:

Combined immunodeficiency

CVID:

Common variable immunodeficiency

ESID:

European Society for Immunodeficiencies

FMF:

Familial Mediterranean fever

HSCT:

Hematopoietic stem cell transplantation

PID:

Primary immunodeficiency

RSTS:

Rubinstein–Taybi syndrome

SIgAD:

Selective IgA deficiency

USI:

Unclassified syndromic immunodeficiency

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Correspondence to Francesco Saettini.

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The study conformed to the Declaration of Helsinki and was approved by the institutional review boards/ethic committee of Comitato Etico Brianza (Monza, Italy; PID-GENMET).

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Saettini, F., Herriot, R., Prada, E. et al. Prevalence of Immunological Defects in a Cohort of 97 Rubinstein–Taybi Syndrome Patients. J Clin Immunol 40, 851–860 (2020). https://doi.org/10.1007/s10875-020-00808-4

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Keywords

  • Rubinstein–Taybi syndrome
  • CREBBP
  • EP300
  • hypogammaglobulinemia
  • antibody deficiency
  • syndromic immunodeficiency
  • humoral defects
  • lymphoproliferation
  • B cells