JCEM_CHROMOGRANIN_A_EBERT-KAHALY_SUPPLEMENTARY_TABLE

The glycoprotein Chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as marker of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed. CgA serum levels were evaluated in 807 subjects in a cross-sectional study, of whom 385 had endocrine and 197 non-endocrine autoimmunity, and 32 NET, to investigate its utility as a marker of autoimmunity. Serum CgA concentrations were increased in 65.6%, 39.3%, 38.4%, and 23.5% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared to 49 healthy controls (C) and 82 euthyroid subjects with thyroid nodules (TN), odds ratios for positive CgA levels were 27.4, 15.9, 7.82 (all p < 0.0001) and 4.29 (p = 0.0034) in patients with NET, T1D, AG and AP, respectively. In AG, CgA and serum gastrin correlated positively (r = 0.55, p < 0.0001). The area under receiver operating characteristic curve to predict AG was higher for parietal cell antibody (PCA) positivity than for CgA (0.84 versus 0.67, p < 0.0001). However, in combination with PCA and intrinsic factor autoantibodies (IFA), CgA independently improves prediction of AG (odds ratio 6.5, p = 0.031). Further, for the first time, we describe that smoking significantly increases CgA serum levels by 21%. CgA qualifies as a novel biomarker for T1D, AP, and especially AG.