Severe combined immunodeficiency (SCID): An overview
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Associate Professor of Pediatrics
- Harvard Medical School
The term "primary immunodeficiency" denotes diseases resulting from inherited defects of the immune system. Many distinct disorders have been described . Combined immunodeficiency syndromes are a heterogeneous group of disorders arising from a disturbance in the development and function of both T and B cells (cellular and humoral immunity). Combined immunodeficiencies are termed "severe" when they lead to early death from overwhelming infection, typically in the first year of life.
An overview of severe combined immunodeficiency (SCID), including clinical manifestations and diagnosis, is presented here. The major combined immunodeficiencies, including multiple causes of SCID, are discussed in detail separately. (See "Severe combined immunodeficiency (SCID): Specific defects" and "X-linked severe combined immunodeficiency (SCID)" and "Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis" and "T-B-NK+ SCID: Pathogenesis and genetics" and "Severe combined immunodeficiency (SCID) with JAK3 deficiency" and "ZAP-70 deficiency" and "Combined immunodeficiencies" and "CD3/T cell receptor complex disorders causing immunodeficiency".)
The humoral immunodeficiencies and disorders involving phagocytic and complement defects are presented separately. (See "Primary humoral immunodeficiencies: An overview" and "Primary disorders of phagocytic function: An overview" and "Inherited disorders of the complement system".)
A study using data from newborn screening for T cell lymphopenia in the United States found an incidence of 1 in 58,000 live births (95% CI, 1 in 46000 to 1 in 80,000) for typical SCID, leaky SCID, and Omenn syndrome . The incidence of autosomal recessive SCID is higher in cultures in which consanguineous marriage is common [3,4]. (See 'SCID classification' below and "Newborn screening for primary immunodeficiencies".)
SCID is a syndrome caused by mutations in different genes whose products are crucial for the development and function of both T and B cells. In some cases, the molecular defect results in only T cell deficiency, while B cells are normal. However, serious T cell dysfunction precludes effective humoral immunity since B cells require signals from T cells to produce antibody.
- Al-Herz W, Bousfiha A, Casanova JL, et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol 2014; 5:162.
- Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA 2014; 312:729.
- Suliaman F, Al-Ghonaium A, Harfi H. High incidence of severe combined immune deficiency in the Eastern Province of Saudi Arabia. Pediatr Asthma Allergy Immunol 2006; 19:14.
- Al-Herz W, Al-Mousa H. Combined immunodeficiency: the Middle East experience. J Allergy Clin Immunol 2013; 131:658.
- Liston A, Enders A, Siggs OM. Unravelling the association of partial T-cell immunodeficiency and immune dysregulation. Nat Rev Immunol 2008; 8:545.
- Shearer WT, Dunn E, Notarangelo LD, et al. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol 2014; 133:1092.
- Griffith LM, Cowan MJ, Notarangelo LD, et al. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol 2009; 124:1152.
- Barron MA, Makhija M, Hagen LE, et al. Increased resting energy expenditure is associated with failure to thrive in infants with severe combined immunodeficiency. J Pediatr 2011; 159:628.
- Dadi HK, Simon AJ, Roifman CM. Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency. N Engl J Med 2003; 349:1821.
- Patel NC, Hertel PM, Estes MK, et al. Vaccine-acquired rotavirus in infants with severe combined immunodeficiency. N Engl J Med 2010; 362:314.
- Filipovich AH, Mathur A, Kamat D, Shapiro RS. Primary immunodeficiencies: genetic risk factors for lymphoma. Cancer Res 1992; 52:5465s.
- Mueller BU, Pizzo PA. Cancer in children with primary or secondary immunodeficiencies. J Pediatr 1995; 126:1.
- Shapiro RS. Malignancies in the setting of primary immunodeficiency: Implications for hematologists/oncologists. Am J Hematol 2011; 86:48.
- Müller SM, Ege M, Pottharst A, et al. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood 2001; 98:1847.
- Buckley RH. Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Immunol Res 2011; 49:25.
- Tabori U, Mark Z, Amariglio N, et al. Detection of RAG mutations and prenatal diagnosis in families presenting with either T-B- severe combined immunodeficiency or Omenn's syndrome. Clin Genet 2004; 65:322.
- Myers LA, Patel DD, Puck JM, Buckley RH. Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood 2002; 99:872.
- Lipstein EA, Vorono S, Browning MF, et al. Systematic evidence review of newborn screening and treatment of severe combined immunodeficiency. Pediatrics 2010; 125:e1226.
- Brown L, Xu-Bayford J, Allwood Z, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood 2011; 117:3243.
- Kwan A, Puck JM. History and current status of newborn screening for severe combined immunodeficiency. Semin Perinatol 2015; 39:194.
- Borzutzky A, Crompton B, Bergmann AK, et al. Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter. Clin Immunol 2009; 133:287.
- Hanson IC, Shearer WT. Ruling out HIV infection when testing for severe combined immunodeficiency and other T-cell deficiencies. J Allergy Clin Immunol 2012; 129:875.
- Papadopoulou-Alataki E, Hassan A, Davies EG. Prevention of infection in children and adolescents with primary immunodeficiency disorders. Asian Pac J Allergy Immunol 2012; 30:249.
- Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol 2004; 22:625.
- Antoine C, Müller S, Cant A, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99. Lancet 2003; 361:553.
- Naik S, Nicholas SK, Martinez CA, et al. Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. J Allergy Clin Immunol 2016; 137:1498.