Clusterin expression and germinal center morphometry help distinguish idiopathic multicentric castleman disease from select lymphadenopathies.

Idiopathic multicentric Castleman disease (iMCD) is a heterogeneous cytokine storm disorder involving systemic inflammation, multicentric lymphadenopathy with characteristic histopathology, and life-threatening multiple organ dysfunction. Patients can present with symptoms ranging from thrombocytopenia, anasarca, fever/elevated C-reactive protein (CRP), reticulin myelofibrosis, renal dysfunction, and organomegaly (iMCD-TAFRO) to thrombocytosis, hypergammaglobulinemia, and plasmacytosis (iMCD-IPL), with patients not falling into either group (iMCD-NOS). The molecular mechanisms across the clinical subtypes have not been elucidated and new effective treatments are needed. Here, we performed bulk RNA sequencing and targeted gene expression quantification in lymph node tissue from multiple iMCD clinical subtypes, pathologically related disorders, and controls. We identified 249 upregulated and 42 downregulated genes in iMCD-TAFRO lymph node tissue, which were enriched in the following pathways: angiogenesis, cell proliferation, and various aspects of the humoral and innate immune response. The targeted gene expression analysis revealed shared differentially expressed genes (DEGs) across all three iMCD clinical subtypes, including