Severe combined immunodeficiency

Severe Combined Immunodeficiency (SCID) is a rare, genetically inherited disorder that severely impairs the development and functioning of key immune cells - T cells and B cells. Characterized by a broad range of genetic mutations, SCID manifests with a variety of clinical presentations. It primarily affects the antibody response due to defects in B lymphocytes themselves or the inability of T-helper cells to correctly activate B lymphocytes. This dysfunction hampers both 'arms' of the adaptive immune system, owing to defects in one or more genes.

Clinical Manifestation and Prognosis

Typically, SCID patients exhibit symptoms of severe bacterial, viral, or fungal infections early in life. Common presentations include interstitial lung disease, chronic diarrhea, and failure to thrive. Recurrent ear infections, Pneumocystis jirovecii pneumonia, and extensive oral candidiasis are other frequent manifestations.

SCID is regarded as the most severe type of primary immunodeficiencies with at least nine different known genes whose mutations can lead to a form of SCID. SCID patients are extremely vulnerable to infectious diseases. They are often colloquially referred to as having 'bubble boy disease' or 'bubble baby disease', as their highly compromised immune system necessitates living in a near-sterile environment, much like David Vetter, who gained fame for this reason.

Without treatment, typically in the form of a successful hematopoietic stem cell transplantation, infants with SCID usually succumb to severe, recurrent infections within their first year of life.

Pathophysiology

In SCID, the adaptive immune system, comprising B cells and T cells, is fundamentally impaired. This defect occurs due to mutations in any one of a growing number of identified genes. These mutations disrupt the development and functioning of T cells, B cells, or both, significantly compromising the body's capacity to fight off infections.

The common feature among all forms of SCID is a profound deficiency in T cell function. In some forms, B cells and natural killer (NK) cells may also be affected. For example, in X-linked SCID, one of the most common forms of the disease, the number of B cells is usually normal, but the T cells and NK cells are significantly reduced.

The genetic defects in SCID primarily impact the lymphocyte development, maturation, and signaling processes, leaving affected individuals with few or no functional lymphocytes. As a result, SCID patients lack almost all immune defenses, rendering them extraordinarily susceptible to infections.

Diagnosis

Diagnosis of SCID is often suspected in infants presenting with severe recurrent infections, failure to thrive, and a history of early mortality in siblings. Diagnostic tests focus on immunological analysis, including complete blood count with differential and lymphocyte subset enumeration via flow cytometry.

Further genetic testing can identify the specific mutation causing SCID, which can help guide treatment decisions and offer predictive information for family planning. Prenatal and newborn screening for SCID, particularly the T-cell receptor excision circle (TREC) test, is becoming increasingly prevalent and can lead to earlier diagnosis and improved outcomes.

Treatment

The mainstay of SCID treatment is hematopoietic stem cell transplantation (HSCT), ideally from a matched sibling donor. This treatment can restore immune function and offers the possibility of a full cure.

Gene therapy is another promising avenue of treatment, especially for forms of SCID caused by a single gene defect. This treatment approach involves correcting the genetic defect in the patient's own stem cells, enabling the development of functional immune cells.

While waiting for definitive therapy or when definitive therapy is not possible, prophylactic antibiotics and immunoglobulin replacement therapy can be used to prevent infections. Moreover, rigorous infection control measures are crucial to protect these patients from exposure to pathogens.

See also

• Primary immunodeficiency
• David Vetter
• Adaptive immune system
• B cell
• T cell
• Hematopoietic stem cell transplantation
• Gene therapy

References

Severe combined immunodeficiency Resources
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