Background: Classical Hodgkin lymphoma (cHL) is, in many cases, characterized by pronounced inflammation, with a very high erythrocyte sedimentation rate (ESR) and presence of B-symptoms. In contrast, a number of patients have no signs of inflammation. There is a lack of structured knowledge about the clinical characteristics of these groups as well as understanding of the biological mechanisms behind the different clinical presentations.
Method: We compared patients with a high level of inflammation (ESR>75, n=25) with a group of patients without clear signs of inflammation (normal ESR according to age and sex, n=32). Clinical data was retrieved from medical records and serum samples were analyzed with comprehensive OlinkTM multiplex protein panels (Oncology, Cardiometabolic, Neurology, Inflammation, 1536 proteins in total). All patients from the regional biobank U-CAN, with clinical and proteomic data available were included. Analyses were also made with upper normal level of ESR as a cut off (n=60, n=32). Linear regression was made for each protein adjusted for age, sex and stage, as well as pathway analysis.
Results: No significant differences were seen between the groups regarding sex, age, stage or histology. Proteins that were most significantly overexpressed in the high inflammation groups were LBP, ST6GAL1, PLAG2A, AIFM1, and VWA1. IL-6 was also significantly elevated and IL-6 and LBP were found to be highly correlated. TARC was significantly overexpressed, but not ranked among the proteins with the lowest adjusted p-value.
Discussion: There seems to be two distinct types of cHL, characterized by no vs very high level of inflammation, that are not significantly associated to histology or other clinical characteristics. The elevated expression of LBP in the groups with high inflammation suggests it having a central role in the inflammatory response in cHL. The results also demonstrate a potential linkage with IL-6 which has been described earlier in patients with severe Covid-19 (Messner et al 2020). PLAG2A has been associated with inflammatory diseases such as rheumatoid arthritis, as well as poor prognosis in different gastrointestinal cancers but is not previously described in cHL. Further investigations are underway to clarify the role of each protein and their interactions within the inflammatory response in cHL. The difference in protein expression supports the hypothesis of the two groups being biologically different.
Jeremia Collin, Ragnhild Risebro, Johan Mattsson Ulfstedt, Emma Pettersson, Mats Hellström, Ingrid Glimelius, Mattias Berglund, Gunilla Enblad, Eva Freyhult, Daniel Molin