Gerald Weissmann

Publications (2)0 Total impact

• Article: Rheumatoid arthritis and systemic lupus erythematosus as immune complex diseases.

  Gerald Weissmann
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  ABSTRACT: Rheumatoid factors are 9s IgM autoantibodies directed against the hinge regions of 7s IgG's that have been changed consequent to their encounter with a foreign antigen, such as those produced by oral bacteria. Occasionally self-aggregating 7s IgG's serve this function. When these complexes are taken up by phagocytes in the joint, they form the "RA cell," a cell analogous to the LE cell of Hargraves. The circulating complexes, which activate complement cascades in the joint, are not specific for RA, being found in other rheumatic and autoimmune diseases as well as having a low prevalence in the normal population. Recently, other antigens resulting in autoimmune complex formation with greater specificity for RA have been described. These antibodies, known as anti-cyclic citrullinated peptide (anti-CCP) antibodies recognize citrullinated protein residues, which are present as antigenic determinants in patients with RA. This is in contrast to systemic lupus erythematosus (SLE), another autoimmune disease characterized by immune complexes in the systemic circulation. In the case of SLE, 7s IgG's directed against several nuclear antigens localize mainly in the kidneys and blood vessels. They also produce cerebral and pulmonary disease by activating complement systemically. Genetic defects in the complement cascade associated with SLE result in inadequate clearance of immune complexes as well as apoptotic blebs containing autoantigens.
  Bulletin of the NYU hospital for joint diseases 01/2009; 67(3):251-3.
• Article: The pathogenesis of rheumatoid arthritis.

  Gerald Weissmann
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  ABSTRACT: Rheumatoid arthritis (RA) is due to a combination of phagocytosis and anaphylaxis gone awry. Immune complexes create their havoc via Fc gamma III receptors that signal via the tyrosine phosphorylation immunoreceptor pathway. Anaphylatoxins, mainly C5a, signal via the MEK kinase cascade, and both engage in cross-talk via NF kappa B. Aspirin-III blocks signals sent by both: immune complexes via FCR, and anaphylatoxin via C5 receptors. Drugs that affect both pathways, for example anti-B cell monoclonal antibodies, such as rituximab, and anti-C5 monoclonal antibodies, such as pexelizumab are currently being investigated. We now appreciate that cytokines are important mediators of inflammation in RA but are downstream of the primary insults: immune complexes and anaphylatoxins. We can therefore begin to ask what the antigen or antigens might be that produce IgGs reactive to 7 S or 19 S rheumatoid factors. The primary antigens of RA could well be CPs, formed perhaps by oral bacteria. Once immunoglobulins become recognized by rheumatoid factors, immune complexes form, and these activate anaphylatoxins. Phagocytosis and anaphylaxis are the proximal events of RA.
  Bulletin of the NYU hospital for joint diseases 02/2006; 64(1-2):12-5.