X-linked severe combined immunodeficiency
X -SCID ( severe combined immunodeficiency ), and SCID -X1, is a form of immunodeficiency disease SCID, wherein a mutation in the common interleukin receptor - γ gene and the protein encoded by this gene is common chain (short? C, CD132 ) several interleukin receptors are no longer functional. An example is the interleukin -2 receptor (IL- 2Rγ ). Due to this error (blood stem cells) can not develop precursor T lymphocytes and no NK cells from hematopoietic stem cells. Since, however, (a " sub - class" of T lymphocytes =) are essential for the production of antibodies by B-lymphocytes as a stimulus TH2 cells, the entire adaptive immune system is not only cellular but also the humoral immune system is not able to work, so defective. The gene for the receptor is localized on the X chromosome, and therefore the designation X- SCID. X -SCID is the genetic cause of about 50 % of all SCID cases.
Affected patients are susceptible to infections of any kind, such as pneumonia or meningitis and survive without appropriate medical treatment (or screening in a sterile tent) only briefly.
Forms of treatment
Stem cell transplantation
As with many other autoimmune diseases, e.g., Leukemias, the destruction of the entire immune system is classically performed by chemotherapy ( although this is hardly necessary here ), then lymphocytes are implanted from a suitable donor through a bone marrow transplant, which should then form a new immune system in the patient.
Gene therapy is a more recent experimental method of treatment ( only one gene concerned) seem suitable for the treatment of X -SCID on the basis of the nature of these monogenic disease. Alain Fischer and co-workers from the Paris Hôpital Necker Enfants Malades of 1999-2000 led by a gene therapy to five patients suffering from X -SCID children. To the patient's hematopoietic stem cells (CD34 - positive) were collected, ex vivo, using a retroviral vector ( from the murine leukemia virus) transformed and infused to the patient again. After four months was found in four of the five patient T cells and NK cells. In the fifth patient, the transformation did not succeed and he had to be carried out HLA -incompatible bone marrow transplantation, which also succeeded for [ ]. After a total of 9 out of 10 patients the treatment was successful, the authors published in 2003 an article in which they point out that in two of their patients, " about three years after the gene therapy uncontrolled exponential clonal proliferation of mature T cells [ ... ] in the two youngest patients took place. " The authors carried out as a possible cause of leukemia to the integration of the vector near the LMO2 proto-oncogene promoter. Recent work in the mouse model, however, indicate that the gene could be self- oncogene: 33% of the mice were transformed after 1.5 years of leukemia. The insertional mutagenesis may therefore not have been the only reason for the mutation. The authors argue for long-term studies, since normally follow-up ( follow-up studies ) be terminated after six months. Against the participation of LMO2 in oncogenesis speak also studies showing that LMO2 appears to play no role in the development of lymphocytes.
Gene therapy has so far been applied only in a few cases in patients without HLA-matched donor.