Establishment of prohaptoglobin-specific antibody and haptoglobin detection systems as biomarkers for pancreatic diseases

Fucosylated haptoglobin (Fuc-Hp) has been recognized as a cancer-associated glycoform. We previously established a monoclonal antibody, 10-7G mAb, which detects both Fuc-Hp and its precursor prohaptoglobin (proHp). Recent studies have suggested that proHp itself may serve as a cancer-associated biomarker with clinical implications distinct from those of Fuc-Hp. Importantly, proHp is produced during inflammation and cancer progression and may exert biological activities different from mature haptoglobin. These observations highlight the need for a reagent that can specifically detect proHp. However, to date, no antibody strictly specific to proHp has been available. In this study, we generated a monoclonal antibody, 21-4F mAb, that specifically recognizes human proHp without cross-reactivity to mature Hp. Using 21-4F mAb, we developed a proHp-specific ELISA and integrated it with assays for several types of Hp, enabling independent quantification of three Hp-related isoforms. Serum analyses of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer revealed distinct alterations among these isoforms, and their combined use provided the highest diagnostic performance. Taken together, 21-4F mAb offers a novel analytical tool for investigating the pathophysiological significance of proHp and may contribute to the development of refined biomarker panels for cancer diagnosis and disease monitoring.