Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease?

Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease.

Neo-Nazism in West Germany

The oharaoter of right-wing extremism in the Federal Republic has undergone extensive transformations in the seventies. As electoral support for the extreme Right declined, a whole range of new groupings emerged pursuing a militant extra-parliamentary strategy. Essential charaoteristics are an increasing tendency to use violence and a close ideological affinity to the NSDAP. They attract a growing number of young people. The increasing susceptibility of young people to rightist ideologies coincides with an economic recession of which young people especially are the victims. Widespread ignorance about Nazism and the prevalence of anti-democratic political attitudes constitute important contributary factors and point to a considerable potential for right-extremism in the Federal Republic., This potential can be attributed. to the negative effects of much of the material dealing with the NS past, to serious deficiencies in the area of historical-political education in schools and, above all, to the absence of any :real process of "coming to terms with the past" in the postwar period. Neo-Nazism is not completely isolated from other trends in West German society. Rightist elements within the established party system and broad sections of the population hold similar views and attitudes. This similarity, linked with an over-exaggerated concern with a perceived threat from the extreme Left may explain the absence of any concerted effort to deal with nee-Nazi tendencies. The response of the courts exemplifies a widespread tendency to under-estimate the significance of the extreme Right. Opposition to the Right is restricted primarily to those circles which suffered most under the Nazi regime. The analysis suggests that one must reject the simplistic view that at the present time the Right does not constitute a serious threat to West German democracy. The study evaluates the wide range of views to be found in secondary sources on the subject of neo-Nazism and is :intended, to contribute to the ongoing discussion conceming the potential for right-extremism in West Germany.