Hodgkin's disease: five steps from autoimmunity to cancer

A five-step hypothesis on the pathogenesis of Hodgkin's disease (HD) is presented. Weak immune suppressor activity gives a predisposition for the development of the disease, after which a non-specific immune stimulation can initiate a self-perpetuating uncontrolled stimulation between interdigitating cells (IDCs), macrophages and helper T lymphocytes (TH). The disease spreads to other lymph nodes through the secretion of humoral factors and by migration of cells. The response of the suppressor branch of the immune system is delayed, and comes from areas not yet involved in the disease, primarily from the spleen and bone marrow. Treatment will result in the predominance of the suppressor activity and allow calming of the disease. In a terminal phase, a possible neoplastic transformation of the chronically stimulated immune cells may give rise to frequent extranodal localizations and a rapid progression of the disease.