The Significance of the Thymus Gland

Situated in the upper chest, just in front of the heart, the thymus gland is a vital organ. Its importance lies in facilitating the normal development of specific white blood cells known as T-cells. Stem cells, originating in the bone marrow, migrate to the thymus, where they undergo maturation into functional T cells capable of combating infections. T-cells are pivotal components of the immune system, making the thymus instrumental in instructing the immune system to safeguard the body against the everyday germs in our environment.

Congenital Athymia and Associated Conditions

Children born without a thymus, are said to have congenital athymia. This leads to a form of severe combined immunodeficiency (SCID) with an absence of T cells and a high risk of life-threatening infections. There can be different genetic and environmental causes when children are born with congenital athymia. The most common of these is a condition called DiGeorge Syndrome (DGS). Children diagnosed with DGS typically have a small piece of chromosome 22 missing, so it can also be called 22q11 deletion syndrome. Children affected by DGS can experience problems affecting different health systems of the body and in a small number of children with DGS (around 1 in 100) athymia can occur, this is called complete DGS (cDGS). Another genetic disorder, CHARGE Syndrome, as well as poorly controlled diabetes in mothers during early pregnancy can also lead to a DGS picture and sometimes athymia. There are also a number of very rare causes associated with defects in other genes which are necessary for the development of the thymus gland. Examples of these genes are called FOXN1 and PAX1.

Significance of Newborn Screening for SCID

Newborn screening programs play a crucial role in identifying severe combined immunodeficiency (SCID), detecting the absence of T cells and conditions like athymia, along with common bone marrow defects leading to various SCID types. While these screenings effectively identify athymia, a unique form of SCID, it distinguishes itself from other SCID types as it cannot be rectified through bone marrow transplantation (BMT). Although BMT, particularly with a fully matched family donor, may offer some clinical improvement by transplanting mature T cells, it often falls short in providing long-term immunity necessary for effective infection defense in children lacking a thymus. Therefore, in most athymia cases, the preferred approach involves performing a thymus transplant.

Thymus Transplantation at Great Ormond Street Hospital

Great Ormond Street Hospital for Children (GOSH) stands as one of the two global centers currently specializing in thymus transplantation, extending its services to patients from Europe and beyond. Thymus tissue for transplantation is sourced from donations, particularly from surgeries involving infants with significant heart defects where some thymus tissue may need to be removed. This harvested tissue is then donated, cultivated in the laboratory, and subsequently transplanted into the recipients.

During the thymus transplant procedure, children receive the new thymus tissue from a healthy donor. This transplanted tissue can safely grow within the recipient’s body, allowing the child’s own stem cells to travel from the bone marrow to the new thymus tissue. There, these stem cells undergo development into T cells, acquiring the knowledge of their functions and communication with other immune cells. Gradually, functional T cells are generated, initiating the child’s ability to combat invading germs and restoring their immune system functionality.

While awaiting thymus transplantation, strict infection prevention measures are imperative. Children are kept in rigorous isolation, either at home with their families or, in specific cases, in the hospital if additional health concerns require attention. To safeguard the children, vaccinations are withheld, as some vaccines contain live viruses that could pose a threat to those lacking T cells. Protective medications are administered to prevent infections, and continuous communication between the referring hospitals’ medical teams and the thymus transplantation team is maintained.

The development of new T cell immunity is a gradual process, spanning several months post-transplantation. The implemented precautions persist during this period. The medical teams, including the clinical nurse specialist dedicated to thymus transplantation, remain in constant collaboration, offering support, updates, and reassurance to families during uncertain times.

Complications Following Thymus Transplantation

After thymus transplantation, certain complications may arise. One crucial role of the thymus is to instruct T cells not to target the body’s own tissues. However, since the thymus tissue cannot be perfectly matched with the individual child, this instructional process is not always flawless, leading to potential reactions known as autoimmunity. This reaction primarily impacts another gland, the thyroid. Fortunately, in most instances, autoimmunity can be effectively managed with medication. Great Ormond Street Hospital (GOSH) actively engages in associated research programs to comprehend and mitigate these complications.

With over sixty patients having undergone this treatment at GOSH, a remarkable three-quarters of them have experienced positive outcomes. Many have successfully discontinued protective medications, resumed normal socialization, and attended school without hindrance. The ongoing research endeavors at GOSH underscore the commitment to advancing understanding and minimizing complications associated with thymus transplantation.

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