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.
(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
For a more
detailed description of APECED, press
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.