Chromogranin Serves as Novel Biomarker of Endocrine and Gastric Autoimmunity

Abstract

Abstract Context The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed. Objective To investigate CgA utility as a marker of endocrine autoimmunity. Methods CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology. Results Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy participant controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, the odds ratios (ORs) for positive CgA levels were 27.98, 15.22, 7.32 (all P < 0.0001) and 3.89 (P = 0.0073) 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 the receiver operating characteristic curve to predict AG was higher for parietal cell antibody (PCA) positivity than for CgA (0.84 vs 0.67; P < 0.0001). However, in combination with PCA and intrinsic factor autoantibodies, CgA independently improved prediction of AG (OR 6.5; P = 0.031). An impact of age on CgA positivity and on CgA value was detected (P < 0.0001) while current smoking significantly increased CgA serum levels by 25% (P = 0.0080). Conclusion CgA qualifies as a novel biomarker for T1D, AP, and AG.