Artemis disease, also known as Artemis deficiency, is a severe combined immunodeficiency (SCID) characterized by extreme sensitivity to radiation and a block in the development of T and B cells. It's the most common form of radiosensitive SCID.
Understanding Artemis Disease
Artemis disease stems from pathogenic variants in the DCLRE1C gene, which encodes the Artemis protein. This protein plays a crucial role in DNA repair, particularly in the process of V(D)J recombination, which is essential for the development of functional T and B lymphocytes.
Key Features of Artemis Disease:
- Severe Combined Immunodeficiency (SCID): Affected individuals have a severely compromised immune system, making them highly susceptible to infections.
- Radiosensitivity: Cells are extremely sensitive to ionizing radiation, which can cause DNA damage. This sensitivity complicates treatment options like bone marrow transplantation, as radiation therapy, often part of the conditioning regimen, can be detrimental.
- T- and B-Cell Deficiency: The development of functional T and B cells is blocked, leading to an absence or very low numbers of these crucial immune cells.
Genetic Basis:
The DCLRE1C gene is located on chromosome 10. Mutations in this gene disrupt the function of the Artemis protein. Because SCID is autosomal recessive, an individual must inherit two copies of the mutated gene (one from each parent) to develop the disease.
Clinical Manifestations:
Infants with Artemis disease typically present within the first few months of life with:
- Recurrent and severe infections (e.g., pneumonia, sepsis).
- Failure to thrive.
- Skin rashes.
Diagnosis:
Diagnosis involves:
- Evaluating the number and function of T and B cells.
- Assessing sensitivity to radiation.
- Genetic testing to identify mutations in the DCLRE1C gene.
Treatment:
Treatment strategies include:
- Hematopoietic stem cell transplantation (HSCT): This is the primary curative treatment. However, the radiosensitivity of Artemis-deficient cells necessitates modified conditioning regimens that minimize or eliminate radiation.
- Gene therapy: This is an emerging option, with recent trials showing some promise, though it is still experimental.
- Supportive care: Includes intravenous immunoglobulin (IVIG) to provide passive immunity and prophylactic antibiotics to prevent infections.
In summary, Artemis disease is a severe, inherited immune deficiency characterized by radiosensitivity and a failure of T and B cell development, resulting from mutations in the DCLRE1C gene. Early diagnosis and treatment, especially hematopoietic stem cell transplantation with radiation-reduced conditioning, are critical for improving patient outcomes.
