Nicotinamide phosphoribosyltransferase leukocyte overexpression in Graves’ opthalmopathy

Abstract

To investigate the role of NAMPT/visfatin in euthyroid patients with Graves’ disease without (GD) and with Graves’ ophthalmopathy (GO), we analyzed NAMPT leukocyte expression and its serum concentration. This was a single-center, cross-sectional study with consecutive enrollment. In total, 149 patients diagnosed with Graves’ disease were enrolled in the study. We excluded subjects with hyper- or hypothyroidism, diabetes mellitus, other autoimmune disorders, active neoplastic disease, and infection. The control group was recruited among healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Serum levels of visfatin, TSH, FT4, FT3, antibodies against TSH receptor (TRAb), antithyroperoxidase antibodies, antithyroglobulin antibodies, fasting glucose, and insulin were measured. NAMPT mRNA leukocyte expression was assessed using RT-qPCR. NAMPT/visfatin serum concentration was higher in GD (n = 44) and GO (n = 49) patients than in the control group (n = 40) (p = 0.0275). NAMPT leukocyte expression was higher in patients with GO (n = 30) than in GD patients (n = 27) and the control group (n = 29) (p < 0.0001). Simple linear regression analysis revealed that NAMPT/visfatin serum concentration was significantly associated with GD (β = 1.5723; p = 0.021). When NAMPT leukocyte expression was used as a dependent variable, simple regression analysis found association with TRAb, fasting insulin level, HOMA-IR, GD, and GO. In the stepwise multiple regression analysis, we confirmed the association between higher serum NAMPT/visfatin level and GD (coefficient = 1.5723; p = 0.0212), and between NAMPT leukocyte expression and GO (coefficient = 2.4619; p = 0.0001) and TRAb (coefficient = 0.08742; p = 0.006). Increased NAMPT leukocyte expression in patients with GO might suggest a presently undefined role in the pathogenesis of GO.

Determinants of Visfatin/NAMPT Serum Concentration and its Leukocyte Expression in Hyperthyroidism

“…We have previously observed, that visfatin/NAMPT serum levels were associated with both free thyroid hormones and anti-thyroperoxidase autoantibodies in hypothyroid patients [16]. In addition, we have found visfatin/NAMPT serum elevation in euthyroid Graves' disease, and significant NAMPT leukocyte overexpression in euthyroid patients with Graves' orbitopathy, supporting the potential association of visfatin and thyroid autoimmunity [17]. These observations were in line with other studies presenting an increase of visfatin/NAMPT levels in serum and its overexpression in affected tissues in patients with autoimmune diseases, such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus [18][19][20][21][22].…”

Prevalence of thyroid eye disease in Graves’ disease: A meta‐analysis and systematic review

“…In total, 26,803 patients were included in the review and 10,667 were diagnosed with thyroid eye disease (TED). Articles included mainly originated from Europe (n = 28), 22‐49 Asia (n = 20), 50‐69 North America (n = 7), 70‐76 Oceania (n = 1) 77 and South America (n = 1) 78 . Table 1 summarizes the results of the meta‐analysis, and a summary of the included articles can be found in the appendix.…”

Changes of Nicotinamide Phosphoribosyltransferase Expressions in Thyroid Glands of Patients with Different Thyroid Pathologies

“…We have previously reported NAMPT overexpression in leukocytes of Graves' orbitopathy patients and its correlation with TSH receptor autoantibodies (TRAb) levels [ 10 ]. At the same time, we have observed increased NAMPT/visfatin/PBEF serum concentration in patients with Graves' disease with and without orbitopathy.…”