Severe Combined Immunodeficiency

Bare lymphocyte syndrome I

Bare lymphocyte syndrome II

SCID ( severe combined immunodeficiency engl.; severe combined immunodeficiency ) is a collective term for diseases or syndrome, which have, as a common congenital severe disruption of the immune system. Typical is a malfunction or a lack of T- lymphocytes for all forms of SCID. Thus, a trouble of the cellular immune response in all SCID shapes is limited. Depending on SCID form the functions or the number of B-lymphocytes and NK - cells is defective. Accordingly, the humoral immunity (antibody -based defense ) may be affected. Cause for each SCID forms are congenital defects or faults of genes. The disease manifested by repeated severe infections with "unusual" organisms and developmental delay already in infancy and early childhood. Untreated SCID diseases to run best years in fatal usually within a few months. The symptomatic treatment is the isolation of the patient from pathogens of infectious diseases. The currently only curative treatment is allogeneic blood stem cell transplantation ( transfer of hematopoietic stem cells from another person). New therapeutic methods based on gene therapy to try to correct the different gene defects by introducing a "healthy" gene. These procedures are still in the experimental stage. Your first human application in a particular form of SCID have successfully corrected the underlying gene defect. As a very serious side effect, the emergence of acute leukemias by the introduced gene was observed, so that no other applications currently take place in humans.

• 6.1 Symptomatic therapy
• 6.2 Curative ( healing ) Therapy

Causes

The various forms of SCID are caused by congenital defects in genes. Depending on the form of SCID are individual different genes affected; but it can be affected at the same time, several genes. The genes affected are:

Forms of SCID (classification)

According to the genetic cause and the resulting disturbances of the immune system, the individual SCID forms are named.

Epidemiology (frequency and occurrence)

The incidence of SCID is estimated at 1:50,000 to 1:100,000 newborns.

Hospital and symptoms

The vast majority of SCID forms manifests itself through symptoms already in infancy and early childhood. An occurrence in childhood, adolescence or adulthood is very rare. Typical symptoms of all forms of SCID are

• Failure to thrive in terms of development and growth delay
• Recurrent ( recurrent ) infections, particularly pneumonia
• Chronic diarrhea ( diarrhea )

Diagnosis

The diagnosis of SCID (usually in the form of flow cytometry) observed in clinical suspicion by immunophenotyping. Here, the presence of certain proteins on white blood cells (leukocytes) are detected by means of fluorescence - labeled antibodies or their absence or reduced presence ( expression ) is confirmed. A lack of CD3 expression on leukocytes speaks very strong for the absence of T-lymphocytes and hence for the presence of a SCID. Another limitation of the SCID - form can be obtained by examination of the B- lymphocytes ( protein markers: CD19 or CD20 ) and NK cells ( protein markers: CD56 ) was detected using the same method.

The exact type of SCID can only be performed molecular genetic studies with proof of defining mutations.

Differential Diagnosis

From SCID forms are to be defined

• T- lymphopenias by external factors ( radiation therapy, especially chemotherapy)
• Combined variable immunodeficiencies ( combined variable immunodefiencies )
• HIV infection

Therapy

Symptomatic therapy

Symptomatic therapy consists of minimizing the exposure to infectious pathogens by reverse isolation. On a strict application infants and children were isolated in sterile plastic tents (so-called bubble babies ). Furthermore, infections with antibiotics ( in bacteria ), antifungal combats ( in fungi ) and antivirals (for viruses). It is worth noting that in immunocompetent individuals uncomplicated running infections (eg, rotavirus gastroenteritis) can take severe courses in SCID patients. For antibody deficiency ( mainly IgG) immunoglobulins can also be substituted.

Curative ( healing ) Therapy

The currently only well -proven curative therapy is allogeneic (donor non- patient) blood stem cell transplantation. This can be done either as transplantation of peripheral hematopoietic stem cells or bone marrow transplantation. Transplantation of allogeneic umbilical cord blood contained therein, including hematopoietic stem cells is possible.

In addition to allogeneic blood stem cell transplantation great hopes were placed in the gene therapy of SCID - forms. This should be healthy versions of morbid or mutated genes are introduced into the cells of the immune system by transporting using viral vectors ( carriers ). In addition to some impressive successes in small clinical trials, there was also very serious side effects from the development of acute leukemia in several patients just by the viral vectors. This was caused by the installation of the transferred gene at genetic loci that are thereby oncogenes.

Forecast

Untreated run the vast majority of SCID forms deadly. Under symptomatic treatment was nevertheless possible prolongation of life; a permanent obstruction of infections is not possible with the strictest application of insulation measures and infection treatment or prophylaxis.

A blood stem cell transplantation helps most SCID forms a permanent cure. As a result the associated very intensive treatment (chemotherapy ± total body irradiation to destroy the defective immune system) may lead to complications including malignant diseases. The incidence of these diseases in the long run not yet adequately known for sure, because the follow-up periods not yet over several decades in blood stem cell transplantation in SCID patients.