Abstract

Aims: To develop a highly sensitive immunoassay for PLA2R autoantibodies and study the relationship between PLA2R autoantibodies and autoimmune thyroid disease-associated nephropathy.Methods: We applied a highly sensitive time-resolved fluoroimmunoassay to quantitatively detect the concentration of phospholipase A2 receptor (PLA2R) antibodies in the serum of patients with Graves' disease, Hashimoto's thyroiditis (HT), nephrotic patients with idiopathic membranous nephropathy (IMN), and normal controls. We immunohistochemically analyzed the existing PLA2R target antigen in the thyroid tissue of patients with Graves' disease and HT, as well as the nephridial tissue of nephrotic patients with IMN.Results: PLA2R antibody concentrations in the serum of normal controls, patients with nodular goiter, Graves' disease, and HT, as well as patients with IMN were 1.13 ± 0.43, 1.07 ± 0.22, 2.12 ± 2.11, 8.07 ± 4.74, and 15.91 ± 19.50 mg/L, respectively. PLA2R antibody concentration in the serum and the area under the receiver operating characteristic curve in patients with HT and IMN were increased significantly. Immunohistochemistry revealed obvious staining of PLA2R in tissues from patients with HT, with a positive rate of 66.67%.Conclusions: PLA2R is a potential pathogenic target antigen for HT, and the production of PLA2R antibodies may cause autoimmune thyroid disease-associated nephropathy.

Highlights

  • Autoimmune thyroid disease (AITD) includes Graves’ disease and Hashimoto’s thyroiditis (HT)

  • Because phospholipase A2 receptor (PLA2R) serves as the target antigen of idiopathic membranous nephropathy (IMN), and IMN is associated with AITD, the relationship between PLA2R in AITD should be determined

  • The results showed that the positive rates of urine protein and hematuria in patients with IMN were high, and some patients tested positive for thyroid disease

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Summary

Introduction

Autoimmune thyroid disease (AITD) includes Graves’ disease and Hashimoto’s thyroiditis (HT). Some patients with thyroid disease experience proteinuria for several months or years after confirmation of the disease [1]. HT combined with membranous nephropathy was first reported in 1976 by O’Regan et al [2]; membranous nephropathy can be PLA2R and Autoimmune Thyroid Disease classified as idiopathic and secondary membranous nephropathy according to the disease etiology. Recent studies showed that idiopathic membranous nephropathy (IMN) is generally associated with production of phospholipase A2 receptor (PLA2R) antibodies, indicating that PLA2R is a major target antigen of the disease. In the present study, we used a highly sensitive time-resolved fluoroimmunoassay (TRFIA) technique to establish a quantitative method for detecting and analyzing PLA2R antibodies in the serum of patients with several common thyroid diseases and IMN. We performed immunohistochemical analysis of pathological samples obtained from patients to investigate the clinical significance of AITD in relation to PLA2R

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