The mutation in the TNFSF5 gene causes there to be no recognition of CD40 by CD40 ligand, and thus the T cells do not induce Ig class switching in B cells, so there are markedly reduced levels of IgG, IgA, and IgE, but have normal or elevated levels of IgM. CD40 ligand is also required in the functional maturation of T lymphocytes and macrophages, so patients with this disorder have a variable defect in T-lymphocyte and macrophage effector function, as well as hyper IgM. Type 2
Immunodeficiency with hyper IgM type 2 is caused by a mutation in the Activation-Induced Cytidine Deaminase (AICDA) gene, which is located on the short arm of chromosome 12. The protein that is encoded by this gene is called Activation-Induced Cytidine Deaminase (AICDA) and functions as a DNA-editing deaminase that induces somatic hypermutation, class switch recombination, and immunoglobulin gene conversion in B cells. When a person is homozygous for the mutation in the AICDA gene, the protein fails to function, and thus somatic hypermutation, class switch recombination, and immunoglobulin gene conversion cannot occur, which creates an excess of IgM. Type 3
Immunodeficiency with hyper IgM type 3 is caused by a mutation in the gene that codes for CD40. As mentioned above, CD40 is expressed on the surface of B cells, and its binding to CD40 ligand on activated T cells induces Ig class switching.
This disease is often considered a malfunction of the immune system and can be associated with IgG4-related systemic disease, in which symptoms of autoimmune pancreatitis, retroperitoneal fibrosis and noninfectious aortitis also occur. Such is also the case in Riedel thyroiditis, an inflammation in which the thyroid tissue is replaced by fibrous tissue which can extend to neighbouring structures. Antibodies that attack the thyroid are what causes most types of thyroiditis. It can also be caused by an infection, like a virus or bacteria, which works in the same way as antibodies to cause inflammation in the glands, such as in the case of subacute granulomatous thyroiditis (de Quervain). Certain people make thyroid antibodies, and thyroiditis can be considered an autoimmune disease, because the body acts as if the thyroid gland is foreign tissue. Some drugs, such as interferon, lithium, amiodarone and immune check point inhibitors can also cause thyroiditis. Diagnosis
The most common and helpful way to diagnose thyroiditis is first for a physician to palpate the thyroid gland during a physical examination. Laboratory tests allow doctors to evaluate the patient for elevated erythrocyte sedimentation rates, elevated thyroglobulin levels, and depressed radioactive iodine uptake (Mather, 2007). Blood tests also help to determine the kind of thyroiditis and to see how much thyroid stimulating hormone the pituitary gland is producing and what antibodies are present in the body. In some cases, a biopsy may be needed to find out what is attacking the thyroid. Classification
Thyroiditis is a group of disorders that all cause thyroidal inflammation.