CD83 as a novel prognostic biomarker for diffuse large B-cell lymphoma arising in immune deficiency/dysregulation among rheumatoid arthritis patients treated with methotrexate

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of methotrexate-associated lymphoma arising in immune deficiency/dysregulation (MTX-associated IDD-DLBCL) among rheumatoid arthritis patients treated with MTX and is characterized by frequent spontaneous regression (SR) after MTX withdrawal. However, some patients do not achieve SR and have poor outcomes. Epstein–Barr virus (EBV) infection correlates with frequent SR but does not fully explain clinical heterogeneity. We investigated prognostic factors irrespective of EBV infection status. We analyzed 21 MTX-associated IDD-DLBCL cases applying the nCounter PanCancer Immune Profiling Panel and immunohistochemistry (IHC) to identify predictors of non-SR cases. Ten patients were classified as SR and 11 as non-SR. Gene expression profiling revealed higher expression of CD83, ICOSLG, IL21R, BCL6, CD40, PAX5, CXCR5, CD79A, DMBT1, and TNFRSF13C in non-SR cases. We therefore focused on CD83, which showed the highest fold change and the most significant P value among these markers. Although CD83 is reported to be a surface marker of mature dendritic cells, IHC analysis revealed that CD83 was more frequently expressed on tumor cells than on dendritic cells. High CD83 IHC positivity (≥15%) in tumor cells correlated with mRNA levels and predicted non-SR after MTX withdrawal. Multivariate analysis identified CD83 IHC high expression as an independent predictor of non-SR cases. High CD83 expression is an independent prognostic factor in MTX-associated IDD-DLBCL, and combined evaluation may refine risk stratification and guide clinical decisions.