Increased risk of Graves´ophthalmopathy in patients with increasing TRAb after radioiodine treatment and the impact of CTLA4 on TRAb titres

Abstract

Introduction Treatment of Graves´ disease (GD) with radioiodine increases the risk of developing Graves´ ophthalmopathy (GO), and the link between thyroid and orbital tissue may be the presence of TSH-receptors. Radioiodine increases the titers of TRAb and the aim was to investigate the relationship between GO and TRAb titers after treatment with radioiodine and to define the impact of risk genes. Methods GD patients without ophthalmopathy or previous treatment with radioiodine were prospectively included at treatment with radioiodine for hyperthyroidism. A follow-up was performed 1 year later for the registration of GO development. The study was performed at a University Hospital Clinic; a referral center of all patients treated with radioiodine in the south of Sweden. The main outcome measures were the development of TRAb, anti-TPO, and anti-TG after 3 months and GO after 12 months and relationship to the genetic background (HLA, CTLA-4, and CYR61). Results Three months of radioiodine TRAb titers increased in two thirds of patients (p < 0.0005) but not in the other third. Anti-TPO titers were associated with TRAb (R = 0.362, p < 0.0001) but not anti-TG. At follow-up 1 year later (n = 204) 32 patients developed GO with a proportion of 70% in the group increasing in TRAb titers and 30% in the group with unchanged or lower TRAb titers (p-value < 0.0005). Patients with GO had higher titers of TRAb than patients without GO. CTLA-4 (rs231775 SNP) was significantly (p < 0.005) associated with TRAb titers above the median three months after radioiodine. Conclusions The increase in TRAb titers after treatment with radioiodine is associated with GO and a genetic variation in CTLA-4 is associated with higher titers of TRAb.

New Strategies in the Control of Graves’ Disease

“…However, a phenomenon is observed that contradicts the claim in this paper. This paper says that TRAb level decreases when the high TH level recovers to normal, but it is observed that after radioiodine treatment TRAb temporarily increases and that transient increase in TRAb is associated with the deterioration and the onset of the grave´s ophthalmopathy [26]. The exact cause for that is not yet clear, but the following reasons are possible:…”

The C55A Single Nucleotide Polymorphism in CTLA-4 Gene, a New Possible Biomarker in Thyroid Autoimmune Pathology Such as Hashimoto’s Thyroiditis

“…Regarding GD, it should be emphasized that the CTLA-4 gene is recognized as the most important genetic factor in the development of this pathology, from the perspective of the presence of the A22G point mutation in the CTLA-4 gene [50]. In addition, it is established by researchers in the field that the G/G genotype in the CTLA-4 gene, the A22G polymorphism is an important risk factor for HT-associated ophthalmopathy [50,51].…”

Evaluation of the Abbott Alinity i Thyroid-Stimulating Hormone Receptor Antibody (TRAb) Chemiluminescent Microparticle Immunoassay (CMIA)

“…TRAbs are the diagnostic marker for Graves’ disease, and monitoring pretreatment levels and levels before ceasing therapy provides valuable prognostic information [ 12 ]. High pretreatment TRAb levels are associated with less response to anti-thyroid drugs and higher rates of disease recurrence [ 13 ] as well as a risk of developing Graves’ ophthalmopathy [ 14 , 15 , 16 ]. TRAb levels are measured before cessation of treatment because patterns in TRAb changes can predict the risk of recurrence and guide further management [ 4 , 17 , 18 ].…”