Endocrine Abstracts

Rationale and hypothesis: Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disease which is characterised by chronic mucocutaneous candidiasis and multiple autoimmune endocrinopathies and results from mutations in the autoimmune regulator (AIRE) gene. Approximately 80% of APS1 patients present with hypoparathyroidism which is suggested to result from aberrant immune responses against the parathyroid gland. As patients typically display organ-specific autoantibodies which correlate with a particular clinical manifestation, there has been much research to identify a parathyroid-specific autoantibody target. Previous studies have identified the parathyroid-expressed calcium-sensing receptor (CaSR) and NALP5 as autoantigens in APS1. However, it is unclear if autoantibodies against CaSR or NALP5 are a specific or sensitive marker for APS1-associated hypoparathyroidism.

Methodology: A case–control study including 44 APS1 patients and 38 healthy control subjects. Methods included ELISA; radioligand binding assays; immunoprecipitation assays; DNA sequencing; and statistical analysis.

Findings: CaSR and NALP5 autoantibodies were detected in 16/44 (36%) and 13/44 (30%) of APS1 patients, respectively, but not in healthy control subjects. No statistically significant association was found between the presence of CaSR or NALP5 autoantibodies and hypoparathyroidism (P>0.05). The detection of CaSR and NALP5 autoantibodies had specificities of 83 and 50%, and sensitivities of 39 and 26%, respectively, for the diagnosis of hypoparathyroidism. There were no significant associations between the presence of CaSR or NALP5 autoantibodies and either sex, age, or age at disease presentation (P values were >0.05). However, a significant association between a shorter APS1 duration (<10 years) and positivity for CaSR autoantibodies was noted (P=0.019). This was not the case for NALP5 autoantibodies.

Conclusions: Since CaSR and NALP5 autoantibodies are not specific or sensitive markers for hypoparathyroidism in APS1, further investigations are required to identify a useful diagnostic marker for this clinical manifestation in APS1.

Disclosure: The research is funded by University of Jazan, Saudi Arabia.