Abstract P068

Plasma Proteomic Profiling of Classical Hodgkin Lymphoma

Background: The proteomic landscape of classical Hodgkin lymphoma (cHL) remains incompletely explored. Plasma proteomics may provide insight into disease biology, diagnosis, and prognosis. Using Olink protein panels, we performed large-scale analysis of protein expression in plasma from cHL patients and healthy controls (HC). Additionally, cHL is often accompanied by systemic inflammation, including elevated erythrocyte sedimentation rate (ESR) and B-symptoms, though not all patients present with these features. Inflammatory response does not uniformly correlate with tumor stage, with discordant cases occurring in both directions. Hence, the inflammatory proteomic profile in cHL was also investigated.

Aims: This study aims to characterize the plasma proteomic profile of cHL in comparison with HC and identify protein patterns associated with the presence or absence of an inflammatory response.

Methods: The plasma proteome (1443 proteins) from 115 cHL patients and 122 HC was compared using age- and sex-adjusted linear regression with multiple testing correction. Inflammatory (n=77) and non-inflammatory (n=38) subtypes were defined by elevated ESR. Inflammatory group differences were assessed using estimated marginal means and partial least squares discriminant analysis. Selected findings will be validated by ELISA.

Results: The results revealed 675 significantly differentially expressed proteins in cHL plasma. Beyond established markers such as TARC, PD1, PDL1, and CD30, we identified VWF and ATP5IF1 as markedly elevated across the cohort, while the suggested tumor suppressor protein CRTAC1 was reduced compared to HC. The inflammatory subtype was characterized by increased expression of many immune mediators, among them proteins associated with an antibacterial response, including LBP, CD14, DEFA1_DEFA1B, and PLA2G2A. In contrast, the non-inflammatory subtype showed higher expression of immune suppressive proteins VTCN1, CD83, FASLG, and PLA2G7. ELISA results will be ready before the conference.

Conclusions: Large-scale proteomic analysis revealed pronounced alterations in the plasma proteome of cHL compared to HC. This study confirms known cHL markers, while also identifying novel findings. Furthermore, the two inflammatory states show distinct differences in plasma proteome expression. The inflammatory subtype is characterized by elevation of antibacterial-associated proteins, while the non-inflammatory subtype displays a more immunosuppressive profile.