Pathogenesis of multi-organic failure in autoimmune diseases.

Abstract

Multi-organic failure in the context of autoimmune diseases is a multi-factorial condition where different pathways concur to produce a global system breakdown. Some of these pathways include the coagulation, fibrinolysis, kinin and complement cascades which in normal conditions work together to provide a comprehensive response to injury. In pathologic conditions these regulatory mechanisms are replaced by positive feed-back loops. The common response pattern is the activation of the immune system via endothelium activation. Furthermore, these different plasma-driven mechanisms may induce standardised endothelial cell responses of which the most relevant are the activation of p38, JNK, NF-kbeta and IRF-3 pathways. In this paper we review the common points between these major pathways and how they become activated, contributing to a global clinical picture. We present two examples of apparently different clinical settings, caused by the same global dysfunction: the Macrophage Activation Syndrome and the iatrogenic "cytokine storm" triggered by the administration of anti-CD28 monoclonal antibody TGN1412 in a phase 1 trial.

• Authors: M C Amaral, J Delgado Alves
• Journal: Autoimmunity reviews (Autoimmun Rev) Vol. 8 Issue 6 Pg. 525-8 (May 2009) ISSN: 1873-0183 [Electronic] Netherlands
• PMID: 19186222 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CD28 Antigens
• Cytokines
• TGN-1412

Topics

• Animals
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Autoimmune Diseases (immunology, physiopathology, therapy)
• Blood Coagulation
• CD28 Antigens (immunology)
• Child
• Clinical Trials as Topic
• Cytokines (genetics, metabolism)
• Cytotoxicity, Immunologic
• Feedback, Physiological
• Humans
• Macrophage Activation Syndrome (blood, immunology, physiopathology)
• Multiple Organ Failure
• Signal Transduction (immunology)
• Thrombosis