The B-cell arm of the immune system has long been appreciated for its crucial role in pathogen resistance, but in the study of many autoimmune diseases, T cells have dominated the limelight for decades. However, the development of the B-cell-depleting antibody rituximab as a lymphoma therapy has provided a tool to probe the contribution made by B cells in several immune disorders. Recently, the success of B-cell depletion with rituximab in the treatment of rheumatoid arthritis has stimulated investigation of its effects in several other immune disorders, and considerable interest in the potential of drugs that can modulate B-cell function for the treatment of such diseases in general. This article discusses the role of B cells in a range of autoimmune disorders, including rheumatoid arthritis and systemic lupus erythematosus, and analyses approaches to therapeutic B-cell manipulation.

B cells move to centre stage: novel opportunities for autoimmune disease treatment

Extracts from the plant Synadenium carinatum latex are widely and indiscriminately used in popular medicine to treat a great number of inflammatory disorders and although the mechanisms underlying these effects remain undefined, the lectin isolated from S. carinatum latex (ScLL) is thought to be in part responsible for these anti-inflammatory effects. In order to elucidate possible immunoregulatory activities of ScLL, we investigated the effects of ScLL administration in models of acute and chronic inflammation. Oral administration of ScLL significantly inhibited neutrophil and eosinophil extravasation in models of acute and chronic inflammation and reduced eosinophil and mononuclear blood counts during chronic inflammation. ScLL administration reduced IL(interleukin)-4 and IL-5 levels but increased interferon-γ and IL-10 in an asthma inflammatory model, which suggested that it might induce a TH2 to TH1 shift in the adaptive immune response. ScLL also inhibited IκBα degradation, a negative regulator of proinflammatory NF-κB. Taken together, these results provide the first description of a single factor isolated from S. carinatum latex extract with immunoregulatory functions and suggest that ScLL may be useful in the treatment of allergic inflammatory disorders.

Anti-asthmatic potential of a d-galactose-binding lectin from Synadenium carinatum latex

In the present review of airway remodelling and its response to therapies, clinical observations about airway physiological abnormalities, assumed to be caused by remodelling processes, are related to what is known about the components of structural changes from airway sampling and histopathological analysis. The review focuses on three important diseases: asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome (BOS), which occurs commonly after lung transplantation as a manifestation of chronic rejection. The present authors chose to use BOS as an issue, because with routine bronchoscopic surveillance after lung transplantation there has been more opportunity to directly study airway pathology longitudinally than in more everyday conditions. In addition, the present authors have reviewed animal models of induced airway remodelling, where most information is available on the potential of therapeutic intervention. Finally, the limited information that can be gained from the literature on the effects of commonly used airway medications on remodelling components is reviewed. In conclusion, the present authors have detailed some of the gaps in knowledge surrounding the potential to improve or modulate remodelling processes in human disease. The areas where it is believed urgent research needs to be focused have also been highlighted.

https://erj.ersjournals.com/content/erj/30/3/574.full.pdf

Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling

Nonpharmacological and pharmacological interventions to prevent or reduce airway

According to the network theory antibodies may act as antigens thus generating anti-idiotypic antibodies that can function as regulators of immune responses. Designed ankyrin repeat proteins (DARPins) are a new class of binding proteins and may serve as an alternative to antibodies. Selections from large DARPin libraries against the variable regions of a murine monoclonal anti-human IgE antibody, termed BSW17, yielded two highly specific anti-idiotypic DARPins both with high affinity. Their binding characteristics were comparable with these of a previously selected anti-idiotypic antibody. In vitro cell assays showed that the anti-idiotypic DARPins were able to inhibit the binding of BSW17 to cell-bound IgE and prevented BSW17 functional activity. These experiments demonstrate the possibility to isolate anti-idiotypic DARPins recognizing idiotypic determinants analogous to antibodies. In the future these DARPins may be further analyzed for their potential as putative vaccine candidates.

Designed ankyrin repeat proteins as anti-idiotypic-binding molecules.

Understanding of the cellular and molecular mechanisms in asthma has lead to the recognition of a number of potential therapeutic targets, a few of which have been evaluated in clinical studies. Parenteral administrations of both anti-IL-5 and IL-12 inhibit eosinophil recruitment to the airways, but display a lack of clinical efficacy. Interrupting the IL-4 pathway thus far has also shown disappointing results in clinical studies. Omalizumab is the first anti-IgE monoclonal antibody developed for the treatment of moderate to severe asthmatics to receive FDA approval. In a number of clinical trials treatment with omalizumab was associated with moderate improvements in a number of relevant endpoints, including the rate of occurrence of disease exacerbations. Newer DNA-based therapeutic strategies including DNA vaccination and the antisense oligonucleotides show promise but thus far have only been tested in animal models.

/pdf/anti-ige-and-other-new-immunomodulation-based-therapies-for-106tiggag3.pdf

Anti-IgE and other new immunomodulation-based therapies for allergic asthma.

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Anti-IgE and other new immunomodulation-based therapies for allergic asthma.