Endocrine Abstracts

Summary: The autoimmune polyglandular syndromes (APS) comprise a wide spectrum of autoimmune disorders and are divided into a very rare juvenile (APS 1) and a relatively common adult type with (APS 2) or without adrenal failure (APS 3). APS 1 is caused by mutations in the autoimmune regulatory (AIRE) gene on chromosome 21 and is inherited in an autosomal recessive manner. Mutations of the AIRE gene result in defective proteins which cause autoimmune destruction of target organs by disturbing the immunological tolerance of the patients. Genetic testing may identify patients with APS 1, but not those with APS 2 and 3. For APS 2/3, susceptibility genes are known which increase the risk for developing autoimmune disorders, but without being causative. These are certain HLA genes, the cytotoxic T lymphocyte antigen (CTLA-4)gene, and the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene on chromosomes 6, 2, and 1, respectively. Actual diagnosis of APS involves serological measurement of organ-specific autoantibodies and subsequent functional testing.

Our patients: We present the history of a 30-year-old monozygotic female twin pair. One of them (KDN) had Hashimoto’s thyroiditis as first manifestation of APS and, 4 years later, Addison’s disease occured and gestational diabetes was found during her first pregnancy. The first clinical sign of the second patient (NDN) was type 1 diabetes with severe hyperglycemia and, at the same time, hypothyroidism was also found due to Hashimoto’s thyroiditis, which was followed with Addison’s disease 5 years later. These monozygotic twins presenting polyglandular autoimmunity had different manifestations of diabetes mellitus although they were HLA-identical. Genetic testing was performed for trying to find the difference in their genome and subseptibility genes.

Results: The DNA chip data showed in both patients insertion in the 12. chromosome (q21.1) and gain of ANTXRL gene the GDM (KDN) positive patient (pseudogene) and different LCHSs (loss of heterozygosity) in both patients. The RNA chip and real time PCR data revealed in the patient with T1DM (NDN) overexpression of the IFNinduced transmembrane protein, IFNγR 2, HLA DOB, PTPN2

Key words: Polyglandular autoimmune syndrome, HLA identical twins, variability of clinical manifestation, genetics.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.