For a study, it was determined that MCD-TAFRO (multicentric Castleman disease–thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal failure, and organomegaly) was an emerging phenotype defined by lymphoproliferation, fluid collection, hemocytopenia, and multiple organopathy. Despite research demonstrating an abnormal blood cytokine/chemokine profile known as “chemokine storm,” the cause remained unknown. Using serum cytokine/chemokine profiles for a study, researchers attempted to discover pathogenic important molecules, possible diagnostic targets, and therapeutic indicators in MCD-TAFRO. In 6 patients with MCD-TAFRO in remission or non-remission, they performed a targeted cytokine/chemokine multiplex study. They found substantial differences in blood concentrations of CCL2, CCL5, and Chitinase-3-like-1 in MCD-TAFRO patients in active vs inactive states. Glycogen synthase kinase 3 (GSK3) and CCR6, which was expressed in megakaryocytes, were discovered as upstream positive regulators for activating MCD-TAFRO status in an ingenuity pathway analysis. 

Patients with MCD-TAFRO had more GSK3+CCR6+ cells, such as megakaryocytes, in their bone marrow than those with systemic lupus erythematosus, MCD-not otherwise defined, or autoimmune hemophagocytic lymphohistiocytosis. The cellularity of GSK3+CCR6+ cells was linked to disease activities, including anemia and thrombocytopenia. Finally, bone marrow cells GSK3 and CCR6 were shown to be implicated in the etiology of MCD-TAFRO and might be used as diagnostic and therapeutic indicators.