Skip to content
2000
image of The Role of Various Autoantibodies and Alpha2-Macroglobulin in Patients with Hashimoto Disease: Does the Presence of Elevated Antibodies Correlate with Alpha 2-Macroglobulin Levels in Hashimoto Disease?

Abstract

Introduction

Autoimmune Thyroiditis (AIT) is caused by defects in the immune system in people with a genetic predisposition to the disease. The most prevalent type of autoimmune thyroiditis is Hashimoto's thyroiditis (HT). The present article reviews the possible relationship between α2-macroglobulin levels and autoantibodies in patients suffering from Hashimoto's disease.

Methods

A total of 170 patients with Hashimoto's disease, categorized into subclinical (96 patients) and manifest (74 patients) forms, were enrolled in the study. The control group comprised 65 individuals without thyroid pathologies or other autoimmune diseases. The levels of α2-macroglobulin and autoantibodies, including both organ-specific and non-organ-specific, were determined in all study participants.

Results

Organ-specific antibody and α2-macroglobulin levels were elevated in all patients studied compared to controls. Analysis of organ non-specific antibody levels in patients revealed elevated levels of antibodies to double-stranded (native) DNA in both the subclinical and manifest groups of patients. There were no statistically significant differences in antibody levels to single-stranded (denatured) DNA between the total patient group and the control groups.

Discussion

The data obtained demonstrated that there is no significant correlation between α2-macroglobulin levels and autoantibody titres, as well as the severity of autoimmune thyroiditis. This finding suggests that α2-macroglobulin may have an unlikely role in the pathogenesis or as a biomarker of disease activity, including in the presence of antibody-dependent cellular damage. Conversely, antibodies directed against double-stranded DNA have exhibited enhanced informativeness and can be regarded as potential markers of the severity of autoimmune thyroid lesions.

Conclusion

Consequently, α2-macroglobulin has no diagnostic value as an indicator of autoimmune process exacerbation in Hashimoto's thyroiditis. Conversely, the presence and level of antibodies to double-stranded DNA may offer a means to assess the severity of the disease and should be the focus of further studies as prognostic markers.

Loading

Article metrics loading...

/content/journals/cpps/10.2174/0113892037374562250730060143
2025-08-25
2025-11-17
Loading full text...

Full text loading...

References

  1. Ragusa F Fallahi P Elia G. Hashimoto's thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Pract. Res. Clin. Endocrinol. Metab. 2019 33 6 101367 10.1016/j.beem.2019.101367
    [Google Scholar]
  2. Rahimova R. Relationship between CTLA4, TNF-α and PTPN22 gene polymorphism and the serum levels of antithyroglobulin and antiperoxidase antibodies in autoimmune thyroiditis. AIMS Med. Sci. 2023 10 1 14 23 10.3934/medsci.2023002
    [Google Scholar]
  3. Ates I. Arikan M.F. Altay M. Yilmaz F.M. Yilmaz N. Berker D. Guler S. The effect of oxidative stress on the progression of Hashimoto’s thyroiditis. Arch. Physiol. Biochem. 2018 124 4 351 356 10.1080/13813455.2017.1408660 29185364
    [Google Scholar]
  4. Radetti G. Clinical aspects of Hashimoto’s thyroiditis. Endocr. Dev. 2014 26 158 170 10.1159/000363162 25231451
    [Google Scholar]
  5. Vargas-Uricoechea H. Nogueira J.P. Pinzón-Fernández M.V. Schwarzstein D. The usefulness of thyroid antibodies in the diagnostic approach to autoimmune thyroid disease. Antibodies 2023 12 3 48 10.3390/antib12030048 37489370
    [Google Scholar]
  6. Mancino G. Miro C. Di Cicco E. Dentice M. Thyroid hormone action in epidermal development and homeostasis and its implications in the pathophysiology of the skin. J. Endocrinol. Invest. 2021 44 8 1571 1579 10.1007/s40618‑020‑01492‑2 33683663
    [Google Scholar]
  7. Fenneman A. C. Bruinstroop E. Nieuwdorp M. van der Spek A. H. Boelen A. A comprehensive review of thyroid hormone metabolism in the gut and its clinical implications. Thyroid 2023 33 1 32 44 10.1089/thy.2022.0491
    [Google Scholar]
  8. Takasu N. Yoshimura Noh J. Hashimoto’s thyroiditis: TGAb, TPOAb, TRAb and recovery from hypothyroidism. Expert Rev. Clin. Immunol. 2008 4 2 221 237 10.1586/1744666X.4.2.221 20477052
    [Google Scholar]
  9. Umar H. Muallima N. Adam J.M. Sanusi H. Hashimoto’s thyroiditis following Graves’ disease. Acta Med. Indones. 2010 42 1 31 35 20305330
    [Google Scholar]
  10. Nishihara E. Amino N. Kudo T. Ito M. Fukata S. Nishikawa M. Nakamura H. Miyauchi A. Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases. Endocr. J. 2017 64 10 955 961 10.1507/endocrj.EJ17‑0164 28768936
    [Google Scholar]
  11. Skevaki C. Wesemann D.R. Antibody repertoire and autoimmunity. J. Allergy Clin. Immunol. 2023 151 4 898 900 10.1016/j.jaci.2023.02.008 36813185
    [Google Scholar]
  12. Hu S. Rayman M. P. Multiple nutritional factors and the risk of Hashimoto's thyroiditis. Thyroid 2017 27 5 597 610 10.1089/thy.2016.0635
    [Google Scholar]
  13. Jin B. Wang S. Pathogenesis markers of Hashimoto's disease—A mini review. Front. Biosci. 2022 27 10 297 10.31083/j.fbl2710297
    [Google Scholar]
  14. Pisetsky D.S. Garza Reyna A. Belina M.E. Spencer D.M. The interaction of anti-DNA antibodies with DNA: Evidence for unconventional binding mechanisms. Int. J. Mol. Sci. 2022 23 9 5227 10.3390/ijms23095227 35563617
    [Google Scholar]
  15. Pedro A. Romaldini J. Americo C. Takei K. Association of circulating antibodies against double-stranded and single-stranded DNA with thyroid autoantibodies in Graves’ disease and Hashimoto’s thyroiditis patients. Exp. Clin. Endocrinol. Diabetes 2006 114 1 35 38 10.1055/s‑2005‑873005 16450315
    [Google Scholar]
  16. Ruan Y. Heng X. Yang L. He W. Li L. Wang Z. Huang S. Chen Q. Han Z. Relationship between autoimmune thyroid antibodies and anti-nuclear antibodies in general patients. Front. Endocrinol. 2024 15 1368088 10.3389/fendo.2024.1368088 38590826
    [Google Scholar]
  17. Rahimova R. Dashdamirova G. Shahverdiyeva I. Yagubova V. Bayramova N. Neuroendocrine and immune interaction in autoimmune thyroiditis. Arch. Euromedica 2023 13 3 1 7 10.35630/2023/13/3.309
    [Google Scholar]
  18. Granito A. Muratori L. Tovoli F. Muratori P. Diagnostic role of anti-dsDNA antibodies: Do not forget autoimmune hepatitis. Nat. Rev. Rheumatol. 2021 17 4 244 10.1038/s41584‑021‑00573‑7 33462415
    [Google Scholar]
  19. Weetman A.P. An update on the pathogenesis of Hashimoto’s thyroiditis. J. Endocrinol. Invest. 2021 44 5 883 890 10.1007/s40618‑020‑01477‑1 33332019
    [Google Scholar]
  20. Mincer D.L. Jialal I. Hashimoto Thyroiditis. StatPearls. Treasure Island, FL StatPearls Publishing 2024
    [Google Scholar]
  21. Segni M. Pucarelli I. Truglia S. Turriziani I. Serafinelli C. Conti F. High prevalence of antinuclear antibodies in children with thyroid autoimmunity. J. Immunol. Res. 2014 2014 1 6 10.1155/2014/150239 24741574
    [Google Scholar]
  22. Siriwardhane T. Krishna K. Ranganathan V. Jayaraman V. Wang T. Bei K. Rajasekaran J.J. Krishnamurthy H. Exploring systemic autoimmunity in thyroid disease subjects. J. Immunol. Res. 2018 2018 1 7 10.1155/2018/6895146 30911555
    [Google Scholar]
  23. Franco J.S. Amaya-Amaya J. Anaya J. Chapter 30 M. Thyroid disease and autoimmune diseases. Autoimmunity: From Bench to Bedside Anaya J.M. Shoenfeld Y. Rojas-Villarraga A. Bogota, Colombia El Rosario University Press 2013
    [Google Scholar]
  24. Wrońska K. Hałasa M. Szczuko M. The role of the immune system in the course of hashimoto’s thyroiditis: The current state of knowledge. Int. J. Mol. Sci. 2024 25 13 6883 10.3390/ijms25136883 38999993
    [Google Scholar]
  25. Zhang Q.Y. Ye X.P. Zhou Z. Zhu C.F. Li R. Fang Y. Zhang R.J. Li L. Liu W. Wang Z. Song S.Y. Lu S.Y. Zhao S.X. Lin J.N. Song H.D. Lymphocyte infiltration and thyrocyte destruction are driven by stromal and immune cell components in Hashimoto’s thyroiditis. Nat. Commun. 2022 13 1 775 10.1038/s41467‑022‑28120‑2 35140214
    [Google Scholar]
  26. Vandooren J. Itoh Y. Alpha-2-macroglobulin in inflammation, immunity and infections. Front. Immunol. 2021 12 Dec 803244 10.3389/fimmu.2021.803244 34970276
    [Google Scholar]
  27. Yao Z. Guo F. Tan Y. Zhang Y. Geng Y. Yang G. Wang S. Causal relationship between inflammatory cytokines and autoimmune thyroid disease: A bidirectional two-sample Mendelian randomization analysis. Front. Immunol. 2024 15 1334772 10.3389/fimmu.2024.1334772 38571956
    [Google Scholar]
  28. Pyzik A. Grywalska E. Matyjaszek-Matuszek B. Roliński J. Immune disorders in Hashimoto’s thyroiditis: What do we know so far? J. Immunol. Res. 2015 2015 1 8 10.1155/2015/979167 26000316
    [Google Scholar]
  29. Efendiyev A.M. Azizova G.I. Dadashova A.R. Investigation of some endogenous antimicrobial peptides in thalassemia. Thalassemia Reports 2018 8 2 7744 10.4081/thal.2018.7744
    [Google Scholar]
  30. Marshall J.S. Warrington R. Watson W. Kim H.L. An introduction to immunology and immunopathology. Allergy Asthma Clin. Immunol. 2018 14 S2 49 10.1186/s13223‑018‑0278‑1 30263032
    [Google Scholar]
  31. Paknys G. Kondrotas A.J. Kevelaitis E. Hasimoto tiroidito rizikos veiksniai ir patogeneze. Medicina 2009 45 7 574 583 10.3390/medicina45070076 19667753
    [Google Scholar]
  32. Cater J.H. Wilson M.R. Wyatt A.R. Alpha-2-macroglobulin, a hypochlorite-regulated chaperone and immune system modulator. Oxid. Med. Cell. Longev. 2019 2019 1 9 10.1155/2019/5410657 31428227
    [Google Scholar]
  33. Gulhar R. Ashraf M.A. Jialal I. Physiology, acute phase reactants. StatPearls. Treasure Island, FL StatPearls Publishing 2024
    [Google Scholar]
  34. Siddiqui T. Zia M.K. Ali S.S. Ahsan H. Khan F.H. Insight into the interactions of proteinase inhibitor- alpha-2-macroglobulin with hypochlorite. Int. J. Biol. Macromol. 2018 117 401 406 10.1016/j.ijbiomac.2018.05.112 29778882
    [Google Scholar]
  35. Gámez A. Yuste-Checa P. Brasil S. Briso-Montiano Á. Desviat L.R. Ugarte M. Pérez-Cerdá C. Pérez B. Protein misfolding diseases: Prospects of pharmacological treatment. Clin. Genet. 2018 93 3 450 458 10.1111/cge.13088 28671287
    [Google Scholar]
  36. Garcia-Ferrer I. Marrero A. Gomis-Rüth F.X. Goulas T. α2-Macroglobulins: Structure and function. Subcell. Biochem. 2017 83 149 183 10.1007/978‑3‑319‑46503‑6_6 28271476
    [Google Scholar]
  37. Targovnik H.M. Scheps K.G. Rivolta C.M. Defects in protein folding in congenital hypothyroidism. Mol. Cell. Endocrinol. 2020 501 110638 10.1016/j.mce.2019.110638 31751626
    [Google Scholar]
  38. Ajmal M.R. Protein misfolding and aggregation in proteinopathies: Causes, mechanism and cellular response. Diseases 2023 11 1 30 10.3390/diseases11010030 36810544
    [Google Scholar]
  39. Erge E. Kiziltunc C. Balci S.B. Atak Tel B.M. Bilgin S. Duman T.T. Aktas G. A novel inflammatory marker for the diagnosis of hashimoto’s thyroiditis: Platelet-count-to-lymphocyte-count ratio. Diseases 2023 11 1 15 10.3390/diseases11010015 36810529
    [Google Scholar]
  40. Merle N.S. Church S.E. Fremeaux-Bacchi V. Roumenina L.T. Complement system part I – molecular mechanisms of activation and regulation. Front. Immunol. 2015 6 262 10.3389/fimmu.2015.00262 26082779
    [Google Scholar]
  41. Rehman A.A. Ahsan H. Khan F.H. α-2-macroglobulin: A physiological guardian. J. Cell. Physiol. 2013 228 8 1665 1675 10.1002/jcp.24266 23086799
    [Google Scholar]
  42. Wallace D.F. The regulation of iron absorption and homeostasis. Clin. Biochem. Rev. 2016 37 2 51 62 28303071
    [Google Scholar]
  43. Thornton C.A. Morgan G. Innate and adaptive immune pathways to tolerance. Nestle Nutr. Inst. Workshop Ser. 2009 64 45 61 10.1159/000235782 19710514
    [Google Scholar]
  44. Szklarz M. Gontarz-Nowak K. Matuszewski W. Bandurska-Stankiewicz E. Iron: Not Just a Passive Bystander in AITD. Nutrients 2022 14 21 4682 10.3390/nu14214682 36364944
    [Google Scholar]
  45. Chang R. Chu K.A. Lin M.C. Chu Y.H. Hung Y.M. Wei J.C.C. Newly diagnosed iron deficiency anemia and subsequent autoimmune disease: A matched cohort study in Taiwan. Curr. Med. Res. Opin. 2020 36 6 985 992 10.1080/03007995.2020.1748585 32223346
    [Google Scholar]
  46. Rayman M.P. Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc. Nutr. Soc. 2019 78 1 34 44 10.1017/S0029665118001192 30208979
    [Google Scholar]
  47. Monko T.R. Tripp E.H. Burr S.E. Gunderson K.N. Lanier L.M. Georgieff M.K. Bastian T.W. Cellular iron deficiency disrupts thyroid hormone regulated gene expression in developing hippocampal neurons. bioRxiv 2023 2023.06.17.545408 10.1101/2023.06.17.545408
    [Google Scholar]
  48. Le S.N. Porebski B.T. McCoey J. Fodor J. Riley B. Godlewska M. Góra M. Czarnocka B. Banga J.P. Hoke D.E. Kass I. Buckle A.M. Modelling of thyroid peroxidase reveals insights into its enzyme function and autoantigenicity. PLoS One 2015 10 12 0142615 10.1371/journal.pone.0142615 26623656
    [Google Scholar]
  49. Rahimova R.R. Study of matrix metalloproteinase activity in patients with autoimmune thyroiditis. Ukr. Biochem. J. 2022 94 2 51 56 10.15407/ubj94.02.051
    [Google Scholar]
  50. Malik H.I. Mir A.R. Abidi M. Habib S. Khan F.H. Moinuddin . Preferential recognition of epitopes on peroxynitrite-modified alpha-2-macroglobulin by circulating autoantibodies in rheumatoid arthritis patients. J. Biomol. Struct. Dyn. 2020 38 7 1984 1994 10.1080/07391102.2019.1623073 31179888
    [Google Scholar]
  51. Maklakova T.P. Zorina V.N. Shapel’ T.T. Boiko O.N. Zorina R.M. Zorin N.A. The levels of immunoreactive proteins and cytokines in the blood of the patients presenting with autoimmune thyroid diseases. Prob. Endokrinol. 2014 60 6 1 6 10.14341/probl201460610‑13
    [Google Scholar]
  52. Shokal U. Eleftherianos I. Evolution and function of thioester-containing proteins and the complement system in the innate immune response. Front. Immunol. 2017 8 759 10.3389/fimmu.2017.00759 28706521
    [Google Scholar]
  53. Alfadda A. Benabdelkamel H. Masood A. Jammah A. Ekhzaimy A. Differences in the plasma proteome of patients with hypothyroidism before and after thyroid hormone replacement: A proteomic analysis. Int. J. Mol. Sci. 2018 19 1 88 10.3390/ijms19010088 29301248
    [Google Scholar]
  54. Rekvig O.P. The anti-DNA antibodies: Their specificities for unique DNA structures and their unresolved clinical impact—A system criticism and a hypothesis. Front. Immunol. 2022 12 808008 10.3389/fimmu.2021.808008 35087528
    [Google Scholar]
  55. Elnady B.M. Kamal N.M. Shaker R.H.M. Soliman A.F. Hasan W.A. Alghamdi H.A. Algethami M.M. Jajah M.B. Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases. Medicine 2016 95 38 4336 10.1097/MD.0000000000004336 27661011
    [Google Scholar]
  56. Wang X. Xia Y. Anti-double stranded DNA antibodies: Origin, pathogenicity, and targeted therapies. Front. Immunol. 2019 10 1667 10.3389/fimmu.2019.01667 31379858
    [Google Scholar]
/content/journals/cpps/10.2174/0113892037374562250730060143
Loading
/content/journals/cpps/10.2174/0113892037374562250730060143
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: Autoimmune thyroiditis ; antibodies ; Hashimoto's thyroiditis ; Ab-nDNA ; Ab-dDNA ; α2-macroglobulin
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test