Endocrine Abstracts

Introduction: Graves’ disease (GD) is the most common cause of hyperthyroidism. The first-choice therapy is administration of thyreostatic drugs. However, approximately half of patients relapse within two years of discontinuation. It is then necessary to decide whether to re-initiate thyreostatic treatment, which may have serious side effects, or to choose a radical approach (TTE, radioiodine). Familial forms of GD indicate that the disease has a significant genetic component. The autoimmune nature of GD refers to the human leukocyte antigen complex (HLA). Within HLA, some variants of DRB1, DQA1 and DQB1 genes appear to be possible predictors of GD development and recurrence. The aim of our work was to introduce a reliable methodology for testing the HLA background of GD. Assessment of its predictive potential on the disease recurrence in long-term follow-up would make it easier for physicians and patients to choose an optimal therapeutic approach.

Methods: In 50 patients treated in the Institute of Endocrinology with GD, the sequencing was chosen as the most reliable haplotyping method. In the three HLA candidate genes (DRB1, DQA1 and DQB1), exon 2 was amplified as the part of the HLA molecule determining its antigenic properties. Amplification of DNA sequences required the group-specific S2, S3 and S4 kits (PentaGen, Protrans - Germany). NGS was performed on MiSDefault (Illumina).

Results: Concerning the patients with recurrence (n=24), the predisposing allelic groups were equally distributed ranging from no risk allele to four risk alleles. Unfortunately, patients who have not yet relapsed and whose remission lasts for more than 2 years are represented by only two individuals, one carrying no risk allele and the other carrying one risk allele. Fisher’s exact test identified allelic group DQA1*05 to be close to statistical significance in terms of the ability to predict the recurrence (P=0.06). The remaining patients in the current cohort (n=24) can not yet be included in the statistical analysis as they are still being treated or their remission period has not yet reached two years of duration.

Conclusion: We reliably classified the HLA DRB1, DQA1 and DQB1 allelic groups in first 50 patients with GD. Low number of patients in long-term remission does not yet allow to quantify the allele-associated risk of the disease relapse. However, the DQA1*05 appears to be the most promising recurrence predictor.

Grant support: MH CR - DRO (EÚ, 00023761), MEYS CR (OP RDE, Excellent research - ENDO.CZ).