Disease and symtoms

.

The members of the association suffer from either one of the two autoimmune conditions with a different background but with relatively large similarity in the clinical symptoms.

APECED (Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy, aka APS1; Autoimmune polyendocrinopathy type 1), is a condition that is inherited recessively. It is caused by mutations in the AIRE gene. AIRE  is normally expressed in the thymus, a lymphoid organ just behind the sternum in thoracic cavity. In the presence of Aire,the maturing lymphocytes in the thymus, which would recognize the body’s own structures, will die and thus, the body´s immune apparatus does not attack  its own tissues and cells. In contrast, when AIRE is not expressed, or is defective, (due to the mutation) such lymphocytes, which have the autoimmune capacity, will survive and cause an autoimmune diseases. In APECED, these auto-immune components are numerous, but the most important ones are the failure of the adrenal cortex, responsible for steroid hormone synthesis and the failure of the parathyroid gland, responsible for the parathormone. An additional component of APECED is the mucocutaneous Candida infection.

For a more detailed description of APECED, press here

Addison´s disease or adrenocortical failure, is a condition where the cortical layers of the adrenal glands, situated above the kidneys, stop functioning. Addison´s disease can occur alone, as a sole autoimmune disease but also connected to two other autoimmune diseases, type 1 diabetes mellitus (T1DM) or thyroid diseases. In this case, the diagnosis of APS2 is used.

The adrenal glands are composed of two distinct anatomical sections, and the inner, central part is responsible for adrenalin and noradrenalin synthesis and secretion. The cortex, on the other hand, is the main source of  the steroid hormones, such as the mineralo-corticosteroid aldosterone and the glucocorticosteroids  cortisol and hydrocortisol.

The cortical cells in the adrenal glands express several enzymes that are responsible for the biosynthesis of the steroid hormones. Similar enzymes are found in the gonads, ovaries and testis. The starting molecule for steroid hormones is cholesterol, and the first of the enzymes, “side-chain cleavage” foms pregnenolone out of this. Thereafter, several different hydroxylase enzymes modify the molecule, leading to the production of the different steroids (see figure). These hydroxylase enzymes were shown to be the target of the immune attack in Addison´s disease in the early 1990s (Krohn et al, Lancet, 1992, Uibo and Krohn,       ). It was shown  that antibodies to the 21 alpha -hydroxylase enzyme was specific for solitary Addison´s disease or APS2, while the other enzymes in the biosynthesis scheme, such as the side-chain cleavage enzyme (P450scc) and 17-alpha- hydroxylase was recognized by antibodies in the APECED patients. This fact can be used as a simple diagnostic method to distinguish APECED from APS2 when the failure of the adrenal  is the first and only clinical sign.