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Abstract

  Combined immunodeficiency comprises a heterogeneous group of disorders, characterized by lack of T cell-mediated immunity and impaired B cell function.
  Combined immunodeficiency has most often an early onset, frequently with protracted diarrhea, interstitial pneumonia, recurrent or persistent candidiasis, and failure to thrive.
  Infections are sustained by intracellular pathogens (especially Pneumocystis jiroveci), viruses, bacteria, and fungi.
  Use of live vaccines and of unirradiated blood products is highly contraindicated in infants with severe combined immunodeficiency (SCID).
  Maternal T cell engraftment is common in SCID. It may cause “graft-versus-host”-like features, but may also occur without specific symptoms.
  Family history is of paramount importance. Some combined immunodeficiencies inherited as an X-linked trait, but several autosomal recessive forms exist, which altogether comprise the majority of cases.
  Lymphopenia is a laboratory hallmark of SCID. However, normal lymphocyte count may be observed in some forms of SCID, especially if maternal T cell engraftment is present or if the defect allows for residual T cell development.
  Hypomorphic defects may lead to leaky forms of SCID, with residual T cell development. Autoimmune manifestations are common in this setting.
  Hematopoietic stem cell transplantation is the treatment of choice for SCID, and can cure more than 70% of the affected patients. Promising results have been achieved with gene therapy, although long-term safety remains an issue.

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