Theoretical basis of paraneoplastic autoimmune disorders - (review)

The close correlation found between malignancies and autoimmune disorders suggests that a common pathogenetic mechanism plays a role in both disorders. Recent results obtained by analysis of V-H and V-L genes of autoreactive immunocytes reveal their oligo-clonality. They are essentially autoreactive with developmental antigens since these clones are prepared to recognize normal antigens without somatic mutations. Under the concept that immunity recognize developmental antigens as well as foreign antigens, it is conceivable that auto-reactivity is induced by an autonomy of immunocytes, when antigenic duality between self and non-self is an essential feature of immunity. In this process, autoimmunity due to malignancy is non-teleologic, since autoimmunity programmed a priori within immunocytes is expressed in an autonomic manner caused by cellular selfishness. On the other hand, paraneoplastic autoimmunity with non-immunocyte tumors suggests a mechanism differing from autonomic expansion of immunocytes. In order to explain this phenomenon, there are two possibilities: the first is that tumor cells secrete immune molecules including immunoglobulins and the second is that so-called antigen drive is related with curious MHC expression of tumor cells, with or without molecular mimicry due to somatic mutations. Both mechanisms are essentially non-teleological.