Elevated Immunoglobulin G4 Levels in Patients with Thyroid Eye Disease and Their Clinical Implications

Abstract

The purpose of this study was to assess the relationship between thyroid eye disease (TED) in patients undergoing orbital decompression and immunoglobulin G4 (IgG4) levels. METHODS. A prospective observational cohort study was conducted among 185 consecutive patients who were diagnosed with TED and underwent orbital decompression. Serum levels of IgG4 were measured, and immunohistochemical staining for IgG and IgG4 was performed in orbital adipose tissue. Data related to clinicopathologic features were analyzed. RESULTS. Among the 185 enrolled patients with TED, 64 (34.6%) were IgG4-positive. The IgG4-positive patients were older, had higher clinical activity scores (CAS), and had worse best-corrected visual acuity (BCVA) than the IgG4-negative patients. Higher thyrotropin receptor antibody (TRAb) levels, histopathological IgG4 counts, IgG4/IgG ratios, and dense lymphocyte infiltration were more frequently observed in IgG4-positive than in IgG4-negative patients. Definitive and probable IgG4 subtypes were independently associated with the active stage in patients with TED. CONCLUSIONS. Our data suggest that the IgG4 subtype in TED is common. IgG4-positive patients with TED may be older, have more severe disease, and have higher clinical activity scores. IgG4 may play an important role in the pathogenesis of TED.

Reshaping the Concept of Riedel’s Thyroiditis into the Larger Frame of IgG4-Related Disease (Spectrum of IgG4-Related Thyroid Disease)

“…A differentiation between eye involvement in IgG4-positive Basedow’s disease and IgG4-related ophthalmic disease as part of the IgG4-RD picture is mandatory [ 80 ]. The current medical approach to thyroid eye disease includes the understanding of new pathogenic traits and potential applications of new drugs based on immunomodulation and immunosuppression, including the loop of IgG4 [ 81 , 82 , 83 , 84 , 85 ]. For instance, one study from 2021 revealed on 69 consecutive subjects with Graves’ ophthalmopathy that one third of them had an increased level of serum IgG4 while blood IgG4 correlated with the disease’s activity and severity.…”

Clinical relevance of serum immunoglobulin G4 in glucocorticoid therapy of Graves’ ophthalmopathy

“…There was a low proportion of active GO patients and a lack of high CAS score GO patients (CAS score greater than 3) in the above‐mentioned studies. A recently published study of GO patients who underwent orbital decompression found that the IgG4‐positive subgroup (histopathological or serum IgG4 positive) had higher clinical activity scores (CAS) and worse best‐corrected visual acuity (BCVA) than the IgG4‐negative patients 29 . Our current study, which was specific to Graves’ ophthalmopathy patients, enrolled 69 GO patients with different CAS scores (2 patients had CAS of 0, 5 patients had CAS of 1, 17 patients had CAS of 2, 25 patients had CAS of 3, 11 patients had CAS of 4, 5 patients had CAS of 5, 1 patient had CAS of 6, and 3 patients had CAS of 7) and different severity (22 mild, 40 moderate‐to‐severe and 7 DON patients), in which 23 patients (33.3%) had elevated IgG4 levels.…”

Spettro delle manifestazioni della malattia correlata a IgG4: una revisione della letteratura

“…Malattia oftalmica del sacco lacrimale dovuta a DR-IgG4 DRA-IgG4 oftalmico DR-IgG4 associato a malattia dell'occhio della tiroide Aryasit et al, 2021;Au et al, 2020;Ye et al, 2020.…”