Haptoglobin as a novel predictor of visceral involvement and relapse in adult IgAV patients.

Abstract

Introduction: IgA vasculitis (IgAV) can present as skin-limited or systemic disease, which can be severe in adults. Predictive markers for visceral involvement are suboptimal. Considering haptoglobin's role as an acute phase reactant, we evaluated whether its differential expression in IgAV patients' skin and leukocytes is also reflected systemically in a larger cohort of adult IgAV patients. Additionally, soluble form of haptoglobin scavenger receptor CD163 was measured in IgAV patient serum.

Methods: We re-analyzed RNA sequencing data from leukocytes and skin biopsies of treatment-naïve adult IgAV patients: (1) IgAV nephritis (n = 3), (2) skin-limited IgAV (n = 3), and healthy controls (n = 3). Haptoglobin serum level was measured in 178, and haptoglobin genotyping was performed in 91 treatment-naïve adult IgAV patients. Serum sCD163 was measured in 60 IgAV patients and 22 HC.

Results: Transcriptomic data of leukocytes and skin of IgAV nephritis patients identified haptoglobin as a hub gene, based on protein-protein interaction network. Haptoglobin serum level was elevated in IgAV patients with nephritis or gastrointestinal involvement compared to other IgAV patients. Patients who relapsed during follow-up had decreased haptoglobin serum level at disease presentation compared to non-relapsing patients. Haptoglobin genotyping did not show differences between genotype groups regarding clinical presentation and laboratory parameters. Serum sCD163 was significantly higher in IgAV nephritis patients compared to HC.

Conclusion: We identified haptoglobin as a novel marker of visceral involvement and relapse in adult IgAV, while sCD163 is linked to renal involvement. Further studies will confirm the clinical utility of haptoglobin as biomarker in IgAV. Key Points • Haptoglobin expression is upregulated in leukocytes and skin of adult IgAV with renal involvement. • Haptoglobin serum level is elevated in IgAV patients with visceral involvement. • Patients with IgAV relapse have lower haptoglobin at disease presentation.