A novel immunoassay for neostatin-7 quantifies basement membrane remodeling and reveals an association with reduced pulmonary function in systemic sclerosis

Systemic sclerosis (SSc) is characterized by immune dysregulation, vasculopathy, and excessive extracellular matrix remodeling. Type XVIII collagen in the basement membrane undergoes proteolytic cleavage generating bioactive fragments such as neostatin-7. This study aimed to develop and validate a novel ELISA, NEO7, targeting neostatin-7, an MMP-generated fragment of type XVIII collagen, and to evaluate its clinical relevance in SSc. The competitive ELISA was developed using a monoclonal antibody directed against neostatin-7-specific cleavage site. Technical evaluation included assessments of specificity, precision, accuracy, interference, and stability. Clinical evaluation was performed in serum from 102 SSc patients and 42 healthy controls. The NEO7 assay showed robust technical performance, and levels were significantly elevated in SSc patients compared to healthy controls (p < 0.01). NEO7 was not associated with proximal skin thickening (p = 0.08), defined as skin thickening proximal to metacarpophalangeal joints, but was higher in patients with airway restriction (forced vital capacity < 80%, p < 0.01). ROC analysis demonstrated moderate discrimination of airway restriction (AUROC = 0.70). NEO7 correlated positively with C-reactive protein (r = 0.34, p < 0.01) and was lower in patients receiving immunomodulatory therapy (p < 0.05). These findings identify NEO7 as a candidate biomarker of basement membrane remodeling in SSc.