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Published in: BMC Endocrine Disorders 1/2023

Open Access 01-12-2023 | Vaccination | Case report

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

Authors: Shigemitsu Yasuda, Seiya Suzuki, Shinnosuke Yanagisawa, Hideo Morita, Akifumi Haisa, Atsushi Satomura, Ritsuko Nakajima, Yoichi Oikawa, Ikuo Inoue, Akira Shimada

Published in: BMC Endocrine Disorders | Issue 1/2023

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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.
Literature
2.
go back to reference Scappaticcio L, Pitoia F, Esposito K, Piccardo A, Trimboli P. Impact of COVID-19 on the thyroid gland: an update. Rev Endocr Metab Disord. 2021;22:803–15.PubMedCrossRef Scappaticcio L, Pitoia F, Esposito K, Piccardo A, Trimboli P. Impact of COVID-19 on the thyroid gland: an update. Rev Endocr Metab Disord. 2021;22:803–15.PubMedCrossRef
4.
go back to reference Ohsako N, Tamai H, Sudo T, Mukuta T, Tanaka H, Kuma K, et al. Clinical characteristics of subacute thyroiditis classified according to human leukocyte antigen typing. J Clin Endocrinol Metab. 1995;80:3653–6.PubMedCrossRef Ohsako N, Tamai H, Sudo T, Mukuta T, Tanaka H, Kuma K, et al. Clinical characteristics of subacute thyroiditis classified according to human leukocyte antigen typing. J Clin Endocrinol Metab. 1995;80:3653–6.PubMedCrossRef
5.
go back to reference Stasiak M, Tymoniuk B, Michalak R, Stasiak B, Kowalski ML, Lewinski A. Subacute thyroiditis is associated with HLA-B*18:01, −DRB1*01 and -C*04:01—the significance of the new molecular background. J Clin Med. 2020;9:534.PubMedPubMedCentralCrossRef Stasiak M, Tymoniuk B, Michalak R, Stasiak B, Kowalski ML, Lewinski A. Subacute thyroiditis is associated with HLA-B*18:01, −DRB1*01 and -C*04:01—the significance of the new molecular background. J Clin Med. 2020;9:534.PubMedPubMedCentralCrossRef
6.
go back to reference Dong RP, Kimura A, Okubo R, Shinagawa H, Tamai H, Nishimura Y, et al. HLA-A and DPB1 loci confer susceptibility to Graves’ disease. Hum Immunol. 1992;35:165–72.PubMedCrossRef Dong RP, Kimura A, Okubo R, Shinagawa H, Tamai H, Nishimura Y, et al. HLA-A and DPB1 loci confer susceptibility to Graves’ disease. Hum Immunol. 1992;35:165–72.PubMedCrossRef
7.
go back to reference Popescu M, Ghemigian A, Vasile CM, Costache A, Carsote M, Ghenea AE. The new entity of subacute thyroiditis amid the COVID-19 pandemic: from infection to vaccine. Diagnostics (Basel). 2022;12:960.PubMedCrossRef Popescu M, Ghemigian A, Vasile CM, Costache A, Carsote M, Ghenea AE. The new entity of subacute thyroiditis amid the COVID-19 pandemic: from infection to vaccine. Diagnostics (Basel). 2022;12:960.PubMedCrossRef
8.
go back to reference Trimboli P, Cappelli C, Croce L, Scappaticcio L, Chiovato L, Rotondi M. COVID-19-associated subacute thyroiditis: evidence-based data from a systematic review. Front Endocrinol (Lausanne). 2021;12:707726.PubMedCrossRef Trimboli P, Cappelli C, Croce L, Scappaticcio L, Chiovato L, Rotondi M. COVID-19-associated subacute thyroiditis: evidence-based data from a systematic review. Front Endocrinol (Lausanne). 2021;12:707726.PubMedCrossRef
9.
go back to reference Stasiak M, Zawadzka-Starczewska K, Lewinski A. Clinical manifestation of subacute thyroiditis triggered by SARS-CoV-2 infection can be HLA-dependent. Viruses. 2021;13:2447.PubMedPubMedCentralCrossRef Stasiak M, Zawadzka-Starczewska K, Lewinski A. Clinical manifestation of subacute thyroiditis triggered by SARS-CoV-2 infection can be HLA-dependent. Viruses. 2021;13:2447.PubMedPubMedCentralCrossRef
10.
go back to reference Ippolito S, Gallo D, Rossini A, Patera B, Lanzo N, Fazzino GFM, et al. SARS-CoV-2 vaccine-associated subacute thyroiditis: insights from a systematic review. J Endocrinol Investig. 2022;45:1189–200.CrossRef Ippolito S, Gallo D, Rossini A, Patera B, Lanzo N, Fazzino GFM, et al. SARS-CoV-2 vaccine-associated subacute thyroiditis: insights from a systematic review. J Endocrinol Investig. 2022;45:1189–200.CrossRef
11.
go back to reference Stasiak M, Zawadzka-Starczewska K, Lewinski A. Significance of HLA haplotypes in two patients with subacute thyroiditis triggered by mRNA-based COVID-19 vaccine. Vaccines (Basel). 2022;10:280.PubMedCrossRef Stasiak M, Zawadzka-Starczewska K, Lewinski A. Significance of HLA haplotypes in two patients with subacute thyroiditis triggered by mRNA-based COVID-19 vaccine. Vaccines (Basel). 2022;10:280.PubMedCrossRef
12.
go back to reference Sendur SN, Ozmen F, Oguz SH, Iremli BG, Malkan UY, Gurlek A, et al. Association of human leukocyte antigen genotypes with severe acute respiratory syndrome coronavirus 2 vaccine-induced subacute thyroiditis. Thyroid. 2022;32:640–7.PubMedCrossRef Sendur SN, Ozmen F, Oguz SH, Iremli BG, Malkan UY, Gurlek A, et al. Association of human leukocyte antigen genotypes with severe acute respiratory syndrome coronavirus 2 vaccine-induced subacute thyroiditis. Thyroid. 2022;32:640–7.PubMedCrossRef
13.
go back to reference Bulatova NR, Zayed AA, Hijjawi UQ, Sharkas SG, Bakri FG. Painful subacute thyroiditis occurring after the administration of influenza vaccine and hyaluronic acid dermal filler: a case report. Medicine (Baltimore). 2022;101:e29120.PubMedCrossRef Bulatova NR, Zayed AA, Hijjawi UQ, Sharkas SG, Bakri FG. Painful subacute thyroiditis occurring after the administration of influenza vaccine and hyaluronic acid dermal filler: a case report. Medicine (Baltimore). 2022;101:e29120.PubMedCrossRef
14.
go back to reference Hernan Martinez J, Corder E, Uzcategui M, Garcia M, Sostre S, Garcia A. Subacute thyroiditis and dyserythropoesis after influenza vaccination suggesting immune dysregulation. Bol Asoc Med P R. 2011;103:48–52.PubMed Hernan Martinez J, Corder E, Uzcategui M, Garcia M, Sostre S, Garcia A. Subacute thyroiditis and dyserythropoesis after influenza vaccination suggesting immune dysregulation. Bol Asoc Med P R. 2011;103:48–52.PubMed
15.
go back to reference Jafarzadeh A, Nemati M, Jafarzadeh S, Nozari P, Mortazavi SMJ. Thyroid dysfunction following vaccination with COVID-19 vaccines: a basic review of the preliminary evidence. J Endocrinol Investig. 2022;45:1835–63.CrossRef Jafarzadeh A, Nemati M, Jafarzadeh S, Nozari P, Mortazavi SMJ. Thyroid dysfunction following vaccination with COVID-19 vaccines: a basic review of the preliminary evidence. J Endocrinol Investig. 2022;45:1835–63.CrossRef
17.
go back to reference Pla Peris B, Merchante Alfaro AA, Maravall Royo FJ, Abellan Galiana P, Perez Naranjo S, Gonzalez BM. Thyrotoxicosis following SARS-COV-2 vaccination: a case series and discussion. J Endocrinol Investig. 2022;45:1071–7.CrossRef Pla Peris B, Merchante Alfaro AA, Maravall Royo FJ, Abellan Galiana P, Perez Naranjo S, Gonzalez BM. Thyrotoxicosis following SARS-COV-2 vaccination: a case series and discussion. J Endocrinol Investig. 2022;45:1071–7.CrossRef
18.
go back to reference Suzuki N, Yoshimura Noh J, Sugisawa C, Hoshiyama A, Hiruma M, Kawaguchi A, et al. Therapeutic efficacy and limitations of potassium iodide for patients newly diagnosed with Graves' disease. Endocr J. 2020;67:631–8.PubMedCrossRef Suzuki N, Yoshimura Noh J, Sugisawa C, Hoshiyama A, Hiruma M, Kawaguchi A, et al. Therapeutic efficacy and limitations of potassium iodide for patients newly diagnosed with Graves' disease. Endocr J. 2020;67:631–8.PubMedCrossRef
19.
go back to reference Kamijo K, Togashi K. Development of more sensitive bioassay of TSAb due to the modification of conventional assay and its measurement in M22-TRAb-seronegative graves’ patients. Ann Thyroid Res. 2014;1:5–10. Kamijo K, Togashi K. Development of more sensitive bioassay of TSAb due to the modification of conventional assay and its measurement in M22-TRAb-seronegative graves’ patients. Ann Thyroid Res. 2014;1:5–10.
20.
go back to reference Suzuki S, Midorikawa S, Fukushima T, Shimura H, Ohira T, Ohtsuru A, et al. Systematic determination of thyroid volume by ultrasound examination from infancy to adolescence in Japan: the Fukushima health management survey. Endocr J. 2015;62:261–8.PubMedCrossRef Suzuki S, Midorikawa S, Fukushima T, Shimura H, Ohira T, Ohtsuru A, et al. Systematic determination of thyroid volume by ultrasound examination from infancy to adolescence in Japan: the Fukushima health management survey. Endocr J. 2015;62:261–8.PubMedCrossRef
21.
go back to reference Nishihara E, Amino N, Kudo T, Kohsaka K, Ito M, Fukata S, et al. Moderate frequency of anti-thyroglobulin antibodies in the early phase of subacute thyroiditis. Eur Thyroid J. 2019;8:268–72.PubMedPubMedCentralCrossRef Nishihara E, Amino N, Kudo T, Kohsaka K, Ito M, Fukata S, et al. Moderate frequency of anti-thyroglobulin antibodies in the early phase of subacute thyroiditis. Eur Thyroid J. 2019;8:268–72.PubMedPubMedCentralCrossRef
22.
go back to reference Ishihara T. Acute exacerbation of Hashimoto's thyroiditis. Nihon Rinsho. 2006;Suppl 1:438–40.PubMed Ishihara T. Acute exacerbation of Hashimoto's thyroiditis. Nihon Rinsho. 2006;Suppl 1:438–40.PubMed
23.
go back to reference Iitaka M, Momotani N, Hisaoka T, Noh JY, Ishikawa N, Ishii J, et al. TSH receptor antibody-associated thyroid dysfunction following subacute thyroiditis. Clin Endocrinol. 1998;48:445–53.CrossRef Iitaka M, Momotani N, Hisaoka T, Noh JY, Ishikawa N, Ishii J, et al. TSH receptor antibody-associated thyroid dysfunction following subacute thyroiditis. Clin Endocrinol. 1998;48:445–53.CrossRef
24.
go back to reference Giovanella L, Ruggeri RM, Ovcaricek PP, Campenni A, Treglia G, Deandreis D. Prevalence of thyroid dysfunction in patients with COVID-19: a systematic review. Clin Transl Imaging. 2021;9:233–40.PubMedPubMedCentralCrossRef Giovanella L, Ruggeri RM, Ovcaricek PP, Campenni A, Treglia G, Deandreis D. Prevalence of thyroid dysfunction in patients with COVID-19: a systematic review. Clin Transl Imaging. 2021;9:233–40.PubMedPubMedCentralCrossRef
25.
go back to reference Olivieri B, Betterle C, Zanoni G. Vaccinations and autoimmune diseases. Vaccines (Basel). 2021;9:815.PubMedCrossRef Olivieri B, Betterle C, Zanoni G. Vaccinations and autoimmune diseases. Vaccines (Basel). 2021;9:815.PubMedCrossRef
26.
go back to reference Bostan H, Sencar ME, Calapkulu M, Kayihan S, Hepsen S, Cimsir A, et al. Impact of the COVID-19 pandemic on the incidence, seasonal distribution, and characteristics of subacute thyroiditis. Endocrine. 2022;21:1–8. Bostan H, Sencar ME, Calapkulu M, Kayihan S, Hepsen S, Cimsir A, et al. Impact of the COVID-19 pandemic on the incidence, seasonal distribution, and characteristics of subacute thyroiditis. Endocrine. 2022;21:1–8.
27.
go back to reference Pirola I, Gandossi E, Rotondi M, Marini F, Cristiano A, Chiovato L, et al. Incidence of De Quervain's thyroiditis during the COVID-19 pandemic in an area heavily affected by Sars-CoV-2 infection. Endocrine. 2021;74:215–8.PubMedPubMedCentralCrossRef Pirola I, Gandossi E, Rotondi M, Marini F, Cristiano A, Chiovato L, et al. Incidence of De Quervain's thyroiditis during the COVID-19 pandemic in an area heavily affected by Sars-CoV-2 infection. Endocrine. 2021;74:215–8.PubMedPubMedCentralCrossRef
28.
go back to reference Vojdani A, Vojdani E, Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: implications for autoimmune diseases. Front Immunol. 2020;11:617089.PubMedCrossRef Vojdani A, Vojdani E, Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: implications for autoimmune diseases. Front Immunol. 2020;11:617089.PubMedCrossRef
29.
go back to reference Iwama S, Ikezaki A, Kikuoka N, Kim HS, Matsuoka H, Yanagawa T, et al. Association of HLA-DR, −DQ genotype and CTLA-4 gene polymorphism with Graves’ disease in Japanese children. Horm Res. 2005;63:55–60.PubMed Iwama S, Ikezaki A, Kikuoka N, Kim HS, Matsuoka H, Yanagawa T, et al. Association of HLA-DR, −DQ genotype and CTLA-4 gene polymorphism with Graves’ disease in Japanese children. Horm Res. 2005;63:55–60.PubMed
30.
go back to reference Zawadzka-Starczewska K, Tymoniuk B, Stasiak B, Lewinski A, Stasiak M. Actual associations between HLA haplotype and Graves’ disease development. J Clin Med. 2022;11:2492.PubMedPubMedCentralCrossRef Zawadzka-Starczewska K, Tymoniuk B, Stasiak B, Lewinski A, Stasiak M. Actual associations between HLA haplotype and Graves’ disease development. J Clin Med. 2022;11:2492.PubMedPubMedCentralCrossRef
31.
go back to reference Yanagawa T, Mangklabruks A, Chang YB, Okamoto Y, Fisfalen ME, Curran PG, et al. Human histocompatibility leukocyte antigen-DQA1*0501 allele associated with genetic susceptibility to Graves’ disease in a Caucasian population. J Clin Endocrinol Metab. 1993;76:1569–74.PubMed Yanagawa T, Mangklabruks A, Chang YB, Okamoto Y, Fisfalen ME, Curran PG, et al. Human histocompatibility leukocyte antigen-DQA1*0501 allele associated with genetic susceptibility to Graves’ disease in a Caucasian population. J Clin Endocrinol Metab. 1993;76:1569–74.PubMed
32.
go back to reference Barlow AB, Wheatcroft N, Watson P, Weetman AP. Association of HLA-DQA1*0501 with Graves’ disease in English Caucasian men and women. Clin Endocrinol. 1996;44:73–7.CrossRef Barlow AB, Wheatcroft N, Watson P, Weetman AP. Association of HLA-DQA1*0501 with Graves’ disease in English Caucasian men and women. Clin Endocrinol. 1996;44:73–7.CrossRef
33.
go back to reference Mangklabruks A, Cox N, DeGroot LJ. Genetic factors in autoimmune thyroid disease analyzed by restriction fragment length polymorphisms of candidate genes. J Clin Endocrinol Metab. 1991;73:236–44.PubMedCrossRef Mangklabruks A, Cox N, DeGroot LJ. Genetic factors in autoimmune thyroid disease analyzed by restriction fragment length polymorphisms of candidate genes. J Clin Endocrinol Metab. 1991;73:236–44.PubMedCrossRef
34.
go back to reference Chan SH, Lin YN, Wee GB, Ren EC, Lui KF, Cheah JS. Human leucocyte antigen DNA typing in Singaporean Chinese patients with Graves’ disease. Ann Acad Med Singap. 1993;22:576–9.PubMed Chan SH, Lin YN, Wee GB, Ren EC, Lui KF, Cheah JS. Human leucocyte antigen DNA typing in Singaporean Chinese patients with Graves’ disease. Ann Acad Med Singap. 1993;22:576–9.PubMed
35.
go back to reference Wongsurawat T, Nakkuntod J, Charoenwongse P, Snabboon T, Sridama V, Hirankarn N. The association between HLA class II haplotype with Graves’ disease in Thai population. Tissue Antigens. 2006;67:79–83.PubMedCrossRef Wongsurawat T, Nakkuntod J, Charoenwongse P, Snabboon T, Sridama V, Hirankarn N. The association between HLA class II haplotype with Graves’ disease in Thai population. Tissue Antigens. 2006;67:79–83.PubMedCrossRef
36.
go back to reference Marino M, Latrofa F, Menconi F, Chiovato L, Vitti P. Role of genetic and non-genetic factors in the etiology of Graves’ disease. J Endocrinol Investig. 2015;38:283–94.CrossRef Marino M, Latrofa F, Menconi F, Chiovato L, Vitti P. Role of genetic and non-genetic factors in the etiology of Graves’ disease. J Endocrinol Investig. 2015;38:283–94.CrossRef
37.
go back to reference Jacobson EM, Tomer Y. The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun. 2007;28:85–98.PubMedPubMedCentralCrossRef Jacobson EM, Tomer Y. The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun. 2007;28:85–98.PubMedPubMedCentralCrossRef
38.
go back to reference Ban Y. Genetic factors of autoimmune thyroid diseases in Japanese. Autoimmune Dis. 2012;2012:236981.PubMed Ban Y. Genetic factors of autoimmune thyroid diseases in Japanese. Autoimmune Dis. 2012;2012:236981.PubMed
39.
go back to reference Dechairo BM, Zabaneh D, Collins J, Brand O, Dawson GJ, Green AP, et al. Association of the TSHR gene with Graves’ disease: the first disease specific locus. Eur J Hum Genet. 2005;13:1223–30.PubMedCrossRef Dechairo BM, Zabaneh D, Collins J, Brand O, Dawson GJ, Green AP, et al. Association of the TSHR gene with Graves’ disease: the first disease specific locus. Eur J Hum Genet. 2005;13:1223–30.PubMedCrossRef
40.
go back to reference Hiratani H, Bowden DW, Ikegami S, Shirasawa S, Shimizu A, Iwatani Y, et al. Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves’ disease. J Clin Endocrinol Metab. 2005;90:2898–903.PubMedCrossRef Hiratani H, Bowden DW, Ikegami S, Shirasawa S, Shimizu A, Iwatani Y, et al. Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves’ disease. J Clin Endocrinol Metab. 2005;90:2898–903.PubMedCrossRef
41.
go back to reference Saheb Sharif-Askari N, Saheb Sharif-Askari F, Ahmed SBM, Hannawi S, Hamoudi R, Hamid Q, et al. Enhanced expression of autoantigens during SARS-CoV-2 viral infection. Front Immunol. 2021;12:686462.PubMedPubMedCentralCrossRef Saheb Sharif-Askari N, Saheb Sharif-Askari F, Ahmed SBM, Hannawi S, Hamoudi R, Hamid Q, et al. Enhanced expression of autoantigens during SARS-CoV-2 viral infection. Front Immunol. 2021;12:686462.PubMedPubMedCentralCrossRef
Metadata
Title
HLA typing of patients who developed subacute thyroiditis and Graves’ disease after SARS-CoV-2 vaccination: a case report
Authors
Shigemitsu Yasuda
Seiya Suzuki
Shinnosuke Yanagisawa
Hideo Morita
Akifumi Haisa
Atsushi Satomura
Ritsuko Nakajima
Yoichi Oikawa
Ikuo Inoue
Akira Shimada
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2023
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-023-01287-5

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