Expression of integrin α4β1 and α4β7 on B cells correlates with autoimmune responses in Graves' disease

Int Immunopharmacol. 2024 Dec 5;142(Pt B):113218. doi: 10.1016/j.intimp.2024.113218. Epub 2024 Sep 23.

Abstract

Background: Integrins are upregulated on endothelial cells and T-lymphocytes in autoimmune thyroid disease (AITD), potentially contributing to immune response localization. The role of integrins on B-cells in AITD remains unclear.

Methods: Peripheral blood samples were collected from healthy controls (n = 56), patients with Graves' disease (GD) (n = 37) and Hashimoto's thyroiditis (HT) (n = 52). Ultrasound-guided fine-needle aspiration (FNA) of the thyroid was performed in patients with non-autoimmune thyroid disease (nAITD) (n = 19), GD (n = 11), and HT (n = 40). Integrins α4β7, α4β1, and αEβ7 in B cells were measured by flow cytometry. Serum zonulin levels were quantified via ELISA. Associations of integrins on B cells with thyroid hormones, thyroid autoantibodies, AITD duration, and zonulin were analyzed.

Results: HT patients exhibited lower α4β7 and higher α4β1 expression on B cells compared to healthy controls and GD patients. While α4β7 was predominant on circulating B cells, the dominant integrin expressed on intrathyroidal B cells varied with specific thyroid diseases. In GD patients, α4β7 and α4β1 expression on circulating B cells correlated positively and negatively with thyroid function and thyroid stimulating immunoglobulins (TSI) levels, respectively. Intrathyroidal α4β1+ B cells positively correlated with TSH levels in HT patients. Additionally, serum zonulin was elevated in HT patients, and intrathyroidal α4β7+ B cells and α4β1+ B cells correlated negatively and positively with zonulin levels, respectively. Integrin αEβ7 on B cells showed no significant association with AITD.

Conclusion: Integrins expressed on B cells potentially play a role in the pathogenesis of AITD and might serve as immune biomarkers for the disease.

Keywords: Autoimmune thyroid disease; B cells; Graves’ disease; Hashimoto’s thyroiditis; Integrin.

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / metabolism
  • Cholera Toxin / immunology
  • Enterotoxins / immunology
  • Female
  • Graves Disease* / blood
  • Graves Disease* / immunology
  • Haptoglobins / metabolism
  • Hashimoto Disease / blood
  • Hashimoto Disease / immunology
  • Hashimoto Disease / metabolism
  • Humans
  • Integrin alpha4beta1 / immunology
  • Integrin alpha4beta1 / metabolism
  • Integrins* / metabolism
  • Male
  • Middle Aged
  • Protein Precursors / metabolism
  • Thyroid Gland / immunology
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology

Substances

  • Integrins
  • Integrin alpha4beta1
  • integrin alpha4beta7
  • zonulin
  • Autoantibodies
  • Haptoglobins
  • Protein Precursors
  • Cholera Toxin
  • Enterotoxins