Comprehensive evaluation of hematological inflammatory indices as biomarkers of autoimmune activity in Graves’ disease: associations with TRAb and disease activity

Abstract

Aim Graves’ disease (GD) is an autoimmune disorder characterized by thyroid-specific autoimmunity and systemic inflammation. This study aimed to investigate changes in hematological inflammatory indices during follow-up in patients with GD and to evaluate their associations with thyroid function, thyroid autoantibodies, and disease activity, with particular emphasis on thyrotropin receptor antibody (TRAb) positivity. Methods This retrospective observational study included 161 adult patients with Graves’ disease who were followed at a tertiary referral center. Hematological inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-platelet ratio (NPR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), and C-reactive protein-to-albumin ratio (CAR), were calculated using baseline laboratory data. Changes between diagnosis and follow-up were analyzed. Correlation analyses, receiver operating characteristic (ROC) curve analyses, and multivariable logistic regression models were performed to evaluate the relationships between inflammatory indices, thyroid function, thyroid autoantibodies, and antibody positivity. Results A total of 161 patients with Graves’ disease (mean age 41.9 ± 12.1 years; 81.4% female) were included. During follow-up, serum TSH increased significantly (0.06 ± 0.14 to 1.80 ± 4.94 mIU/L, P < .001), whereas FT3 decreased (6.36 ± 5.26 to 4.01 ± 1.66 pg/mL, P < .001). TRAb (8.11 ± 9.55 to 4.12 ± 5.63 IU/L), anti-TPO (376.16 ± 373.75 to 248.63 ± 287.41 IU/mL), and anti-Tg (172.80 ± 476.78 to 109.24 ± 258.35 IU/mL) levels all declined significantly (all p ≤ 0.003). Hematological inflammatory indices also decreased significantly, including NLR (2.38 ± 0.86 to 1.89 ± 0.63, P < .001), PLR (141.8 ± 38.6 to 129.5 ± 34.2, P = .003), SII (604 ± 221 to 487 ± 176, P < .001), NPR (0.0198 ± 0.0056 to 0.0162 ± 0.0048, P < .001), MHR (0.0127 ± 0.0041 to 0.0104 ± 0.0033, P < .001), and CAR (0.094 ± 0.036 to 0.066 ± 0.027, P < .001). Among the evaluated biomarkers, CAR demonstrated the best diagnostic performance for predicting persistent TRAb positivity at final follow-up (AUC 0.821, 95% CI 0.756–0.886), followed by NPR (adjusted OR = 1.69, 95% CI: 1.09–2.64, P = .025), MHR (AUC 0.782) and NPR (AUC 0.764). In multivariable logistic regression, CAR (adjusted OR 2.58, 95% CI 1.56–4.28, P < .001) and MHR (adjusted OR 2.03, 95% CI 1.26–3.28, P = .004) remained independent predictors of TRAb positivity. Conclusion Routine hematological inflammatory indices reflect systemic immune activation in Graves’ disease and improve following treatment. Among the evaluated biomarkers, CAR demonstrated the strongest and most consistent association with thyroid autoimmunity, while MHR also showed robust independent predictive value. These inexpensive and readily available biomarkers may complement conventional thyroid-specific tests for assessing autoimmune activity and disease severity, although prospective multicenter validation is required before routine clinical implementation.