The use of monoclonal antibodies to treat Castleman's disease.

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder presenting with heterogeneous clinical features and with a complex etiology. MCD incidence is increased in people living with HIV/AIDS when it is causally associated with Kaposi's sarcoma-associated herpes virus (KSHV). HIV-seronegative individuals present with either idiopathic or KSHV-associated MCD. Central to MCD pathology is altered expression and signaling of IL-6, which promotes B-cell proliferation and causes systemic manifestations. KSHV encodes a viral homolog of human IL-6, accounting for its role in MCD, while recent evidence shows an association between IL-6 receptor polymorphisms and idiopathic MCD. The increased understanding of mechanisms underlying the pathogenesis of MCD has guided the use of new monoclonal antibody therapies for treating this complex disorder.