Embed Size (px)
Citation preview
S.Sasson 2016 1
Anti-‐Adrenal Ab Anti-‐adrenal Ab can occur in isolation (Addison’s Disease) or as part of an autoimmune polyendocrine syndrome (APS-‐1/APECED and APS-‐2) Addison’s Disease
• Defined as primary adrenocortical hypo function • 75-‐80% are “idiopathic” i.e. autoimmune Addison’s disease (most common cause of primary hypoadrenalism in developed countries.)
o affects adrenal cortex but spares medulla § Adrenal cortex synthesises aldosterone. cortisol, androgens
o F>M o Peak 40-‐50yrs o Association with HLADRB1*0404 o Associates with other autoimmune diseases o The majority of patients have anti-‐adrenal cortex Ab (ACA)
• Other causes of Addison’s Disease: o TB, other granulomatous disease/sarcoid, haemorrhage, malignancy (infection is the most common cause of primary hypoarenalism world-‐wide)
• Secondary hypoadrenalism is due to hypothalamic/pituitary disease e.g. suppression by endogenous or exogenous steroid.
S.Sasson 2016 2
In autoimmune Addison’s Disease
• Histologically adrenal glands are fibrosed with a mononuclear cellular infiltrate and occasional plasma cells • Tissue destruction is thought to be due to cytotoxic T-‐cells i.e. ACA may NOT be pathological OR may play a role in antibody dependent cell mediated cytotoxicity.
ACA are directed against steroid genic enzymes:
• 21-‐OH is the major antigen, this correlates with the degree of adrenal dysfunction o part of the P450 cytochrome family essential for production of cortisol
• 17-‐a-‐OH an antigen also expressed in gonads and placenta • P450scc antigen (adrenals, gonads, placenta)
S.Sasson 2016 3
Anti Adrenal Cortex Ab (ACA) Methods of detection Assay Principle Notes IIF on primate adrenal gland-‐screening dilution approx. 1:5
• Patient sera is incubates on commercially available tissue slides. Following washing FITC-‐conjugated secondary (detection Ab is incubated). • Detection is via fluorescence microscopy where positive result demonstrates positive homogenous staining and fluorescence intensity greater than a negative control • Stains cytoplasm of all 3 zones of cortex • Note AMA+ may mimic ACA. Therefore samples positive for ACA should be tested for liver, stomach and kidney Ab
Advantages Sensitivity 60% autoimmune Addison’s Disease Specificity 99% Detects 21-‐OG and 17-‐a-‐OH May predict /herald the development of autoimmune Addison’s Disease More widely used method Disadvantages Also positive in:
• up to 18% of TB Addison’s disease • 5% 1st degree relatives of AAD • 15-‐30% pts with CMC,
hyperparathyroidism Note testis, ovaries and placenta tissue may also be positive for 21-‐OH Role in disease pathogenesis unclear Only semi-‐quantitative (titre)
21-‐0H immunoprecipitation/Radioimmunoassay • 2 currently available assays • 35-‐S-‐methionine-‐labelled 21-‐OH • 125-‐I-‐OH (Radioimmunoprecipitation) • One of the above is incubated with
serum and precipitated with protein A sepharose beads
• Analysis by gel electrophoresis
Advantages More sensitive than IIF (78%) Disadvantages Less widely used method Qualitative interpretation
S.Sasson 2016 4
Anti Adrenal Cortex Ab + IIF:
Steroid producing cell Ab (StCA)
• Generic term for Ab that react with cytoplasmic Ag of all cells producing steroids i.e. adrenals, gonads, placenta • Initially described by IIF before the specific Ag were further identifies • 17-‐a-‐OH ab, P450scc and steroid producing cell Ab are usually only found if 21-‐OH Ab are present • Associated with gonadal failure as well as adrenal failure • Found in 100% of pts with AD and ovarian failure • Predict gonadal failure in pt with ACA.
