Biologic response modifiers in primary immunodeficiency disorders

To propose a new classification for the primary immunodeficiency disorders and to review potential therapeutic applications of biologic response modifiers in these disorders.

Relevant articles were identified through a search of MEDLINE using the following indexing terms: primary immunodeficiencies (and subclassifications), and human immunomodulators (and subclassifications).

Articles were critically reviewed and included if relevant.

The primary immunodeficiency disorders are classified according to functional abnormalities, specifically, abnormalities in early cellular maturation, differentiation, regulatory cell function, enzymatic function, and cytokine responses. Such a classification clarifies the potential role of biologic response modifiers in primary immunodeficiency disorders. Intravenous gammaglobulin and histamine-2 (H2)-receptor blockers modify regulatory cell function; retinoids modify abnormal cellular differentiation, gene transfer and enzyme replacement can be applied in disorders characterized by specific functional gene abnormalities; and interferons modify abnormal cytokine responses. Interleukin-2, thymic hormones, transfer factor, and levamisole appear to affect multiple functional defects.

Biologic response modifiers are currently important ancillary tools in the treatment of immunodeficiency disorders, and their therapeutic role will become even more important in the future. Multi-center cooperative trials of new and existing agents are needed to fully define their roles and efficacy in the treatment of these disorders.