Endocrine Abstracts

Introduction: Subacute thyroiditis is a thyroid inflammatory disease, triggered mainly by viral factors in genetically susceptible individuals. Up to 2020, only HLA-B*35 was confirmed as SAT-related. However, obviously in HLA-B*35-negative patients, some other genetic background occurs.

Material and Methods: We performed HLA-typing using high resolution NGS method in different groups of patients with SAT and demonstrated the new association between HLA and SAT in the Caucasian population.

Results: In addition to HLA-B*35, SAT was proved to be associated with the presence of HLA-B*18:01, -DRB1*01 and -C*04:01. In Caucasians, HLA-C*04:01 is in a linkage disequilibrium with HLA-B*35:01/02/03. Therefore, HLA-C*04:01 alone cannot be treated as an independent SAT risk factor due to its linkage with the previously described HLA-B*35. However, the presence of any of the two haplotypes should be considered as a marker of genetic susceptibility to SAT. No such linkage disequilibrium has been described for HLA-B*18:01 or -DRB1*01 so these alleles should be considered new, completely independent SAT risk factors. Moreover, clinical course of SAT also seemed to be HLA-dependent. In regard to US pattern, typically observed multiple hypoechoic blurred lesions were demonstrated to be rarely found in -B*18:01-positive patients. In most cases with HLA-B*18:01 only, unilateral homogenously hypoechoic single SAT area, filling the whole affected lobe and mimicking the large thyroid nodule was observed. This report explained the phenomenon of various US patterns of SAT. Additionally, the risk of SAT recurrence was also reported to be HLA-associated and was significantly higher in patients with co-presence of HLA-B*18:01 and -B*35. In such cases, the steroid treatment should be intensified with slower dose reduction. SARS-CoV-2 is a novel pathogen which can trigger SAT. On the contrary to other viral factors, SAT onset in COVID-19 can be very rapid, and even simultaneous presence of both diseases was described. Our study revealed that this phenomenon can be related to the presence of homozygosity at HLA-B*35. COVID-19 vaccination is also a new factor which can induce SAT. We postulated that SAT occurrence after COVID-19 vaccination can be related to a co-presence of HLA-B*35:03 and -C*04:01.

Conclusions: Our study provided the set of four alleles whose assessment allows confirming the genetic predisposition for SAT in almost all patients. HLA-related background seems to play a crucial role in SAT occurrence as well as its typical of atypical clinical course, including cases induced by SARS-CoV-2 and COVID-19 vaccination.