Subacute Thyroiditis is Associated with HLA-B*18:01, -DRB1*01 and -C*04:01—The Significance of the New Molecular Background

Abstract

Subacute thyroiditis (SAT) is a thyroid inflammatory disease whose pathogenesis is still not completely defined. Previous viral infection is considered to be a triggering factor in genetically predisposed individuals. In about 70% of patients, susceptibility to SAT is associated with the HLA-B*35 allele. The correlation between SAT and other human leukocyte antigens (HLA) has not yet been unequivocally demonstrated and the genetic background is still unknown in about 30% of patients. The purpose of our study was to perform HLA genotyping using a next-generation sequencing method, to find out whether alleles other than HLA-B*35 are correlated with SAT morbidity. HLA-A, -B, -C, -DQB1, -DRB1 were genotyped using a next-generation sequencing method in 1083 subjects, including 60 SAT patients and 1023 healthy controls. Among 60 patients diagnosed with SAT, 81.7% of subjects were identified as having allele HLA-B*35, 23.3% had HLA-B*18:01, 28.3% had HLA-DRB1*01 and 75.5% had HLA-C*04:01. These alleles occurred in the control group at frequencies of 10.2%, 7.2%, 12.9% and 12.5%, respectively. The differences were statistically significant, with p < 0.05. In addition to its previously described relationship with HLA-B*35, genetic susceptibility to SAT was associated with the presence of HLA-B*18:01, DRB1*01 and C*04:01. The alleles HLA-B*18:01 and DRB1*01 were independent SAT risk factors. The assessment of these four alleles allows the confirmation of genetic predisposition in almost all patients with SAT.

New aspects in the pathogenesis and management of subacute thyroiditis

“…Recent improvement of diagnostic methods brought the novel insight into the genetic background. In 2020, our research team demonstrated the new association between HLA and SAT in the Caucasian population [ 10 ]. In addition to the previously described correlation with HLA-B*35 , SAT was proved to be associated with the presence of HLA-B*18:01, -DRB1*01 and -C*04:01 [ 10 ].…”

“…In 2020, our research team demonstrated the new association between HLA and SAT in the Caucasian population [ 10 ]. In addition to the previously described correlation with HLA-B*35 , SAT was proved to be associated with the presence of HLA-B*18:01, -DRB1*01 and -C*04:01 [ 10 ]. In Caucasians, HLA-C*04:01 is in a linkage disequilibrium with HLA-B*35:01/02/03 , i.e.…”

“…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 [ 10 ]. 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.…”

Subakute Thyreoiditis und akute suppurative Thyreoiditis

“…Für eine (post-)virale Genese spricht auch, dass die SAT in vielen Fällen nach Infekten der oberen Atemwege auftritt, wobei die Latenz üblicherweise zwischen 2 und 8 Wochen beträgt [10]. In der Pathogenese der SAT dürfte außerdem auch eine gewisse genetische Prädisposition eine Rolle spielen, da in bis zu 70 % der Fälle eine Assoziation mit HLA-B35 besteht [11]. Durch die entstehende Inflammation kommt es zu einer Beschädigung der Schilddrüsenfollikel sowie zu einer Proteolyse des in den Schilddrüsenfollikeln gespeicherten Thyreoglobulins.…”

Painful Subacute Thyroiditis is Commonly Misdiagnosed as Suspicious Thyroid Nodular Disease

“…2,3 More recent investigations have uncovered an association with the presence of additional antigens, namely, HLA-B*18:01, DRB1*01, and HLA-C*04:01. 4 The annual reported age-and sex-adjusted incidence is 4.9 patients per 100,000 population. 5,6 The distinctive clinical picture includes typical viral symptoms, such as malaise, fever, and myalgias.…”