Disease-related antibodies

The isolation of disease-related antibodies specific for either melanoma [ 180], the autoimmune thyroid peroxidase antigen [174], or neutrophil antigen characteristic of ulcerative colitis [17] from nonnaive patient repertoire phage libraries has been reviewed above in the Panning on cells section. The isolation of anti-viral antibodies with diagnostic or therapeutic potential from antibody repertoire libraries has been described in earlier papers e.g. against HIV [197], hepatitis B virus [198] and human respiratory syncytial virus [199],... 

With a genetic or disease-related predisposition, the intake of medicaments and their subsequent catabolism in the biotransformatory system sometimes lead to the formation of reactive metabolites, (s. p. 55) (s. fig. 3.11) These can bind to components of the cytochrome system. After cytolysis, they may become the target antigens of antibodies, (s. p. 544) (s. fig. 29.1) This has been ascertained, for example, for carbamazepine (LMK 3),... 

In cancer, host antibodies react with a unique group of autologous intracellular proteins known as tumor-associated antigens (TAAs). Additionally, autoimmunity is consistently observed in a variety of well-known autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and insulin-dependent diabetes mellitus. The detection of autoimmunity is useful because autoantibodies can serve as biomarkers for disease, and their presence may help to elucidate the role of significant disease-related biochemical pathways. 

For each infectious disease, antibody levels (if any) in naive, subclinically infected, clinically infected, and immune individuals in the endemic population should be sought. Only in this way can the immunoassayist relate antibody levels to infection. Once these parameters are known, the effect of vaccination in these individuals can be assayed as well as the relationship between protective antibody and immunity. 

Surface-enhanced laser desorption ionization (SELDI) uses so-called protein chips for the detection of peptides and proteins from complex biological fluids such as blood or urine, often for the identification of diagnostic biomarkers for specific carcinomas [156, 157]. These protein chips can contain various media for positive or negative ion exchange or reverse-phase chromatography, as well as specific antibodies or DNA. The functionaUzed surface is immobihzed on a MALDl sample plate for the selective enrichment of constituents of the complex mixture applied, whereas the not bound supernatant is removed by washing. Unfortunately, a large number of unsubstantiated claims for the detection of disease-related biomarkers has discredited this approach, mostly as a result of poor mass spectrometric performance. 

Dulay, S., Lozano-Sanchez, R, Iwoha, E. et al (2011) Electrochemical detection of celiac disease-related anti-tissue transglutaminase antibodies using thiol based surface chemistry. Biosens. Bioelectron., 26, 3852-3856. 

A number of chimerized, humanized, and one human mAb have now been approved for therapeutic use in humans in the treatment of autoimmunity, malignancy, infection and cardiovascular disease (Table 1). Some of the currently licensed mAb will be discussed here. A much larger number of mAb are currently being evaluated in Phase I, II and III trials. In general, chimeric, humanized and human mAb are very well tolerated with few side effects. Chimeric or humanized mAb still have the potential to evoke host immune response to the variable domains or CDRs of the antibody so-called HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody) responses, although these responses are uncommon. Short-lived and occasionally severe infusion-related acute hypersensitivity reactions such as fever, skin itching, shivering, respiratory compromise and low blood pressure sometimes occur-. Such effects may... 

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