Michael McConville

Background: Interstitial lung disease (ILD) is an increasingly recognized manifestation of ANCA-associated vasculitis (AAV) and is associated with substantial morbidity and mortality. The marked biological and clinical heterogeneity of AAV-associated ILD (AAV-ILD) poses major challenges for diagnosis, prognostic stratification, and therapeutic decision-making. Circulating biomarkers have emerged as promising tools for improving disease characterization; however, the available evidence remains limited and fragmented. Methods: We performed a scoping review to summarize the current evidence on circulating biomarkers investigated in AAV-ILD. Peer-reviewed studies evaluating biomarkers associated with ILD occurrence, disease activity, radiological progression, pulmonary function decline, mortality, or treatment response were systematically identified and qualitatively analyzed. Results: Seven observational studies met the inclusion criteria. The identified biomarkers could be broadly classified into three biological categories: epithelial injury biomarkers (KL-6 and SP-D), immune–fibrotic biomarkers (CCL2, CXCL6, CXCL13, and IL-13), and epithelial remodelling biomarkers (CA19-9, CA125, and CYFRA21-1). KL-6 and SP-D were associated across individual studies with pulmonary involvement, disease activity, or relapse, whereas CCL2, CXCL6, CXCL13, and IL-13 were associated with inflammatory and profibrotic processes, radiological abnormalities, or disease progression. Tumour-associated biomarkers were associated with radiological abnormalities and mortality, suggesting that they may reflect aberrant epithelial remodelling rather than malignancy. Across studies, circulating biomarkers showed preliminary associations with disease detection, prognosis, longitudinal disease behaviour, and treatment response; however, their clinical utility has not been prospectively established. Overall, the current evidence is limited by small sample sizes, retrospective study designs, and substantial clinical heterogeneity. Conclusions: Circulating biomarkers represent a promising approach for improving the biological characterization of AAV-ILD and may contribute to the future characterization of inflammatory and fibrotic disease phenotypes. Prospective multicentre studies with independent validation cohorts are required before biomarker-guided management can be implemented in routine clinical practice.

Background: Interstitial lung disease (ILD) is an increasingly recognized manifestation of ANCA-associated vasculitis (AAV) and is associated with substantial morbidity and mortality. The marked biological and clinical heterogeneity of AAV-associated ILD (AAV-ILD) poses major challenges for diagnosis, prognostic stratification, and therapeutic decision-making. Circulating biomarkers have emerged as promising tools for improving disease characterization; however, the available evidence remains limited and fragmented. Methods: We performed a scoping review to summarize the current evidence on circulating biomarkers investigated in AAV-ILD. Peer-reviewed studies evaluating biomarkers associated with ILD occurrence, disease activity, radiological progression, pulmonary function decline, mortality, or treatment response were systematically identified and qualitatively analyzed. Results: Six observational studies met the inclusion criteria, comprising four retrospective and two prospective cohorts. The identified biomarkers could be broadly classified into three biological categories: epithelial injury biomarkers (KL-6 and surfactant protein D [SP-D]), immune–fibrotic biomarkers (C-C motif chemokine ligand 2 [CCL2] and C-X-C motif chemokine ligand 6 [CXCL6]), and epithelial remodelling biomarkers (carbohydrate antigen 19-9 [CA19-9], cancer antigen 125 [CA125], and cytokeratin-19 fragment [CYFRA21-1]). KL-6 and SP-D were consistently associated with pulmonary involvement, disease activity, and relapse, whereas CCL2 and CXCL6 reflected inflammatory and profibrotic pathways linked to disease progression. Tumour-associated biomarkers were associated with radiological abnormalities and mortality,suggesting that they may reflect aberrant epithelial remodelling rather than malignancy. Across studies, circulating biomarkers showed potential utility for disease detection, prognostic stratification, longitudinal monitoring, and therapeutic guidance. However, the current evidence is limited by small sample sizes, retrospective study designs, and substantial clinical heterogeneity. Conclusions: Circulating biomarkers represent a promising approach for improving the biological characterization of AAV-ILD and may facilitate more personalized management strategies by distinguishing inflammatory from fibrotic disease phenotypes. Prospective multicentre studies with independent validation cohorts are required before biomarker-guided management can be implemented in routine clinical practice.