Clustering analysis of serum proteomes of iMCD and related diseases reveals notable heterogeneity. (A) A t-SNE plot visualizing serum proteomes of iMCD, Hodgkin lymphoma (lymphoma), HHV8-associated MCD (HHV8+MCD), and rheumatoid arthritis (RA) patients during active disease. Among the iMCD patients, siltuximab responders (partial response or complete response, per durable clinical and tumor [radiologic lymph node] response criteria as determined in NCT01024036) are indicated with open triangles, nonresponders with closed triangles, and patients for which siltuximab was not given as a monotherapy or response was not assessed by independent clinical trial review are represented by closed circles. Colored lines are drawn around clusters as determined by elastic net with fivefold cross-validation. (B) A revisualization of the t-SNE plot of iMCD and related disease serum proteomes to better indicate iMCD in relation to all other samples. Colored lines are drawn around clusters A to E as determined by elastic net with fivefold cross-validation, and samples within each cluster are colored accordingly. iMCD patients are indicated by a closed upward-facing triangle, and non-iMCD patients are visualized by an open downward-facing triangle. (C) Top 40 serum analytes that best distinguish between clusters A to E, as selected by elastic net with fivefold cross-validation, across iMCD and related disease samples.