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Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM. [ABSTRACT FROM AUTHOR]

Clostridium difficile infection has emerged as a growing worldwide health problem. The colitis of Clostridium difficile infection results from the synergistic action of C. difficile secreted toxins A and B upon the colon mucosa. A human monoclonal IgG anti-toxin has demonstrated the ability in combination therapy to reduce mortality in C. difficile challenged hamsters. This antibody is currently in a clinical trial for the treatment of human Clostridium difficile infection. More than one group of investigators has considered using polyclonal bovine colostral antibodies to toxins A and B as an oral passive immunization. A significant proportion of the healthy human population possesses polyclonal antibodies to the Clostridium difficile toxins. We have demonstrated that polyclonal IgA derived from the pooled plasma of healthy donors possesses specificity to toxins A and B and can neutralize these toxins in a cell-based assay. This suggests that secretory IgA prepared from such pooled plasma IgA may be able to be used as an oral treatment for Clostridium difficile infection. [ABSTRACT FROM AUTHOR]

The human polyclonal IgG antibody preparation known as Intravenous Immunoglobulin (IVIG) has been under study as a potential treatment for Alzheimer's disease (AD) since 2002. Preclinical and clinical studies have shown that IVIG has anti-amyloid and immune modulatory properties relevant to treating neurodegenerative disorders. In early stage AD clinical trials, IVIG was found to reduce cognitive decline and increase brain glucose metabolism. Unfortunately, IVIG failed to meet primary outcome objectives in the North American Phase 3 clinical trial in mild to moderate AD. However, positive cognitive signals were observed in pre-planned subgroup analyses among APOE-ε4 carriers and moderately impaired AD patients. Biomarker studies revealed dose dependent increases in plasma and CSF immunoglobulins and decreases in beta amyloid-42 levels. In addition, IVIG treatment was generally safe and well-tolerated. These findings suggest that naturally occurring human anti-amyloid antibodies may play a physiologic role in the clearance of aggregated amyloid proteins. While the results of clinical trials to date do not provide support for the use of IVIG to treat AD at the doses tested, additional studies of IVIG's mechanisms are warranted and may guide the development of more effective therapies for AD in the future. [ABSTRACT FROM AUTHOR]

Antibodies executing catalytic activity are referred to as antibody enzymes or short 'abzymes' and may have diagnostic relevance. Abzymes with deoxyribonuclease (DNase) activity have been demonstrated in patients with autoimmune and infectious diseases. Despite several reports on the occurrence of DNase abzymes in systemic autoimmune rheumatic diseases, conclusive data about DNase activity of antibodies in patients with spondyloarthritides (SpAs) are lacking. In recent cross-sectional studies evaluating levels of IgG DNase activity in patients with psoriatic arthritis (PsA), reactive arthritis (ReA), and ankylosing spondylitis (AS), DNase activity of IgG has been assessed by the rivanol clot method and confirmed by agarose gel electrophoresis. Remarkably, levels of IgG DNase activity were significantly higher in sera of SpA patients than those in control subjects. In patients with PsA, ReA, and AS, a positive correlation of DNase IgG activity with synovitis, disease activity, and stage of spondylitis was observed, respectively. Given the involvement of autoimmune reactions in cytolysis and connective tissue degradation in PsA, ReA, and to a lesser extent in AS, abzymes might have an impact on the pathophysiology of SpAs. Detection of IgG DNase activity in patients suffering from SpA represents an exciting new research field and may assist in the differential diagnosis of SpA. [ABSTRACT FROM AUTHOR]

It has previously been shown that in multiple myeloma (MM) each IgG paraprotein exhibits a unique oligosaccharide profile. It has been assumed that this results from a clone specific glycosylation machinery. However, the abnormal physiological environment of the bone marrow in this disease may also affect normal plasma cells producing polyclonal IgG. We present data to show that this is so and that, in two cases, the oligosaccharide profile of the polyclonal IgG reflected that of the paraprotein from the same patient rather than that of normal polyclonal IgG. [ABSTRACT FROM AUTHOR]

Fibronectin (Fn) is an adhesive glycoprotein that plays an important role in reticuloendothelial system functioning. Fn binds several macromolecules, it is found in cryoprecipitates obtained from patients with different diseases and it interacts in vitro with immune complexes. The interaction between Fn and polyclonal IgG was characterized by ligand affinity chromatography. After IgG was modified by attachment to a solid matrix or heat aggregation, it was able to interact with either soluble or immobilized Fn, The binding was highly influenced by ionic strength and pH, The estimated affinity constants were 30 × 106M when soluble Fn was applied to solid phase IgG and 2-3 × 107M when aggregated IgG interacted with immobilized Fn. The interaction may be relevant in situations in which immune complexes are involved. [ABSTRACT FROM AUTHOR]