HLA typing of patients who developed subacute thyroiditis and Graves’ disease after SARS-CoV-2 vaccination: a case report

Abstract

Background Cases of subacute thyroiditis (SAT) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination have been reported. A human leukocyte antigen (HLA) allele, HLA-B*35, appears to be involved in the pathogenesis of SAT. Case presentation We conducted HLA typing of one patient with SAT and another with both SAT and Graves’ disease (GD), which developed after SARS-CoV-2 vaccination. Patient 1, a 58-year-old Japanese man, was inoculated with a SARS-CoV-2 vaccine (BNT162b2; Pfizer, New York, NY, USA). He developed fever (38 °C), cervical pain, palpitations, and fatigue on day 10 after vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum C-reactive protein (CRP) and slightly increased serum antithyroid-stimulating antibody (TSAb) levels. Thyroid ultrasonography revealed the characteristic findings of SAT. Patient 2, a 36-year-old Japanese woman, was inoculated twice with a SARS-CoV-2 vaccine (mRNA-1273; Moderna, Cambridge, MA, USA). She developed fever (37.8 °C) and thyroid gland pain on day 3 after the second vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum CRP, TSAb, and antithyroid-stimulating hormone receptor antibody levels. Fever and thyroid gland pain persisted. Thyroid ultrasonography revealed the characteristic findings of SAT (i.e., slight swelling and a focal hypoechoic area with decreased blood flow). Prednisolone treatment was effective for SAT. However, thyrotoxicosis causing palpitations relapsed thereafter, for which thyroid scintigraphy with 99mtechnetium pertechnetate was conducted, and the patient was diagnosed with GD. Thiamazole treatment was then initiated, which led to improvement in symptoms. Conclusion HLA typing revealed that both patients had the HLA-B*35:01, -C*04:01, and -DPB1*05:01 alleles. Only patient 2 had the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles. The HLA-B*35:01 and HLA-C*04:01 alleles appeared to be involved in the pathogenesis of SAT after SARS-CoV-2 vaccination, and the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles were speculated to be involved in the postvaccination pathogenesis of GD.

Graves’ disease after exposure to the SARS-CoV-2 vaccine: a case report and review of the literature

“…The table was categorized according to the sales company of the vaccines. We identified 32 patients who received the Pfizer mRNA vaccine; [ 11 , 18 – 36 ] six patients who received the Moderna mRNA vaccine; [ 20 , 28 , 31 , 37 – 39 ] 12 patients who received mRNA vaccines from unknown companies; [ 40 ] ten patients who received the AstraZeneca vaccine, including those from the Serum Institute of India; [ 37 , 41 – 44 ] and one patient each who received Johnson & Johnson and Sinovac vaccines [ 27 , 38 ]. Characteristically, across all companies, most patients with Graves’ disease are relatively young women, which is consistent with Graves’ disease in general.…”

Subacute thyroiditis following COVID-19 vaccination: Case presentation

“…Human leukocyte antigens (HLA-B35, HLA-C04, and HLA-A11) have been linked to SAT susceptibility and may also play a role in the pathophysiology of SAT associated with COVID-19 immunization. [34][35][36][37][38] It is common for post-vaccine or COVID-19-associated SAT to present clinically. Neck discomfort was the most common clinical symptom of post-COVID-19 vaccine-associated SAT, followed by tiredness, fever, myalgia, and various clinical thyrotoxicosis signs (palpitation, tachycardia, and sweating).…”

Association of HLA-DRB1*11 and HLA-DRB1*12 gene polymorphism with COVID-19 in Burkina Faso

“…[ 30 ], showing that the HLA-DRB1*11 allele is associated with a reduced risk of severe symptoms requiring hospitalization or intensive care. HLA-DRB1*11 was also found to be independently associated with COVID-19(+) and a 40% decrease in the probability of COVID-19(+) in kidney transplant recipients [ 31 ]. In a recent case reports study, HLA-DRB1*11:01 was speculated to be involved in the pathogenesis of Graves’ disease following SARS-CoV-2 vaccination [ 32 ].…”

“…To detect the presence of HLA-DRB1*11 and HLA-DRB1*12 alleles, PCR-SSP was performed using the sequence-specific primers (Table 4 ) originally described by Ma et al. [ 31 ] with a slight modification. Due to the large number and variability of HLA alleles, the amplification reaction included a primer pair designed to target the human growth factor (HGF) housekeeping gene.…”