Immune complex diseases concept

With respect to studies in animal models which dissect the mechanisms of formation, localization, and fate of immune complexes, the mechanisms by which they elicit an inflammatory response, and their biologic activities, we provide little more than summary information required to understand the concept of immune complex disease and the principles of the tests. For more detailed information, the reader is referred to several excellent reviews (C14, H2, Til, Ul, W12). 

Animal models of disease, whether naturally occurring or artificially induced, provide valuable insights into human disease and allow rigidly controlled studies that are not possible in humans. Probably the most intensively studied model of an immune complex disease is the spontaneous lupuslike disease that occurs in certain inbred strains of mice, especially the (NZB x NZW) F, hybrid. Its study has provided insights with respect to genetic predisposition (H25), the role of endogenous retroviruses (D8), the influence of sex hormones (R9), the identification of T suppressor cell abnormalities (T3), and the propensity to form certain autoantibodies, especially to double-stranded DNA (S36) and to the RNA-protein complex, Sm (E2). Though animal studies are not the subject of this review, we emphasize that the entire concept and framework by which we view immune complex disease in humans are based on initial observations in animals. 

While in the original conceptions of immune complex diseases, interaction of antigen with antibody in free solution frequently led to tissue damage, it has become clear that the large majority of immune complexes arising in vivo are probably not pathogenic at all. First, the size and composition of the complex seems to play a... 

Plasmapheresis is primarily used in patients with muscular dystrophy and lately with parkinsonism. However, the use of plasmapheresis in thyroid eye disease has mirrored problems observed in assessing responses in other autoimmune disease. The concept of an immune complex involvement in the pathophysiology of thyroid eye disease is unproven. A study reported 11 patients who received multiple plasmapheresis sessions with systemic prednisone and azathioprine. It noted that this form of... 

Finally, the linear low-dose extrapolation obviates de facto the concept of a threshold in the dose-response curve. The threshold concept is universally accepted for most other, noncancer toxicity and for many other biological phenomena (e.g., taste thresholds), and many scientists would argue that such thresholds (or practical thresholds ) should apply to the cancer or mutation response due to the undo-lying complexities in toxicokinetics and in the dynamics of DNA damage and repair, immune surveillance, and the variation in the progression of clinical diseases. ... 

SemBioSys Genetics Inc. (Calgary, Canada), in addition to insulin and apoHpopro-tein AI, demonstrated a proof-of-concept for proteins addressing osteoporosis, pulmonary and Hver fibrosis, psoriasis and gastrointestinal disorders. Plantigen Inc. (London, Canada) has proof of principle for several products under development Those include glutamic acid decarboxylase (GAD) for the treatment of type 1 diabetes interleukin-10 (IL-10) for treatment of inflammatory bowel disease interleukin-4 (IL-4) for use as adjuvant to enhance immune response and major histocompati-ble complex (MHG) and cytokines for use in organ transplants. 

---