Treatment for<unk><unk> <unk>  can be divided into two main groups, the prophylactic treatment (i.e. preventative) and curative treatment. The former attempts to manage the opportunistic infections common to<unk>  patients and the latter aims at reconstituting healthy T-lymphocyte function. From the late 60s to early 70s, physicians began using "bubbles", which were plastic enclosures used to house newborns suspected to have<unk> S, immediately after birth. The bubble, a form of isolation, was a sterile environment which meant the infant would avoid infections caused by common and lethal pathogens. On the other hand, prophylactic treatments used today for<unk><unk> <unk>  are similar to those used to treat other primary immunodeficiencies. There are three types of prophylactic treatments, namely, the use of medication, sterile environments, and intravenous immunoglobulin therapy (IVIG). First, antibiotics or antivirals are administered to control opportunistic infections, such as fluconazole for candidiasis, and acyclovir to prevent herpes virus infection. In addition, the patient can also undergo intravenous immunoglobulin (IVIG) supplementation. Here, a catheter is inserted into the vein and a fluid, containing antibodies normally made by B-cells, is injected into the patient's body. Antibodies, Y-shaped proteins created by plasma cells, recognize and neutralize any pathogens in the body. However, the IVIG is expensive, in terms of time and finance. Therefore, the aforementioned treatments only prevent the infections, and are by no means a cure for<unk><unk> <unk> . Bone marrow transplantation (BMT) is a standard curative procedure and results in a full immune reconstitution, if the treatment is successful. Firstly, a bone marrow transplant requires a human leukocyte antigen (HLA) match between the donor and the recipient. The HLA is distinct from person to person, which means the immune system utilizes the HLA to distinguish self from foreign cells. Furthermore, a BMT can be allogenic or autologous, which means the donor and recipient of bone marrow can be two different people or the same person, respectively. The autologous BMT involves a full HLA match, whereas, the allogenic BMT involves a full or half (haploidentical) HLA match. Particularly, in the allogenic BMT the chances of graft-versus-host-disease occurring is high if the match of the donor and recipient is not close enough. In this case, the T-cells in the donor bone marrow attack the patient's body because the body is foreign to this graft. The depletion of T-cells in the donor tissue and a close HLA match will reduce the chances of graft-versus-host disease occurring. Moreover, patients who received an exact HLA match had normal functioning T-cells in fourteen days. However, those who received a haploidentical HLA match, their T-cells started to function after four months. In addition, the reason BMT is a permanent solution is because the bone marrow contains multipotent hematopoietic stem cells which become common lymphoid or common myeloid progenitors. In particular, the common lymphoid progenitor gives rise to the lymphocytes involved in the immune response (B-cell, T-cell, natural killer cell). Therefore, a BMT will result in a full immune reconstitution but there are aspects of BMT that need to be improved (i.e. GvHD). Gene therapy is another treatment option which is available only for clinical trials.<unk><unk> <unk>  is a monogenic disorder, the IL2RG gene is mutated, so gene therapy will replace this mutated gene with a normal one. This will result in a normal functioning gamma chain protein of the interleukin receptor. In order to transfer a functional gene into the target cell, viral or non-viral vectors can be employed. Viral vectors, such as the retrovirus, that incorporate the gene into the genome result in long-term effects. This, coupled with the bone marrow stem cells, has been successful in treating individuals with<unk> . In one particular trial by Cavazzana-Calvo et al., ten children were treated with gene therapy at infancy for<unk> . Nine of the ten were cured of<unk> . However, about three years after treatment, two of the children developed T-cell leukemia due to insertion of the IL2RG gene near the LMO2 gene and thereby activating the LMO2 gene (a known oncogene). A third child developed leukemia within two years of that study being published, likely as a direct result of the therapy. This condition is known as insertional mutagenesis, where the random insertion of a gene interferes with the tumor suppressor gene or stimulates an oncogene. There is currently no approved gene therapy on the market, but there are many clinical trials into which<unk>  patients may enroll. Therefore, research in the field of gene therapy today and in the future is needed to avoid the occurrence of leukemia. In particular, research into the use of insulator and suicide genes is warranted as this may prevent cancer from developing. The insulator gene inhibits the activation of adjacent genes. On the other hand, the suicide gene is stimulated when a tumour begins to form, and this will result in the deactivation of the therapeutic gene. Moreover, the use of restriction enzymes such as the zinc-finger nuclease (ZFN) is being studied. The ZFN allows the researcher to choose the site of gene integration. Vector safety is important in the field of gene therapy, hence vectors that self-inactivate the promoter and enhancer (SIN) and adenoviruses that creates no immune response are prominent areas of research for vector biologists.
X-linked severe combined immunodeficiency
Severe combined immunodeficiency
Common variable immunodeficiency
X-linked agammaglobulinemia
Combined immunodeficiencies
Adult-onset immunodeficiency syndrome
Primary immunodeficiency
Chronic granulomatous disease