Immunopathology and the gene therapy of lupus.
Lupus is a chronic autoimmune inflammatory disease with complex clinical manifestations. In humans, lupus, also known as systemic lupus erythematosus (SLE), affects between 40 and 250 individuals, mostly females, in each 100 000 of the population. There are also a number of murine models of lupus widely used in studies of the genetics, immunopathology, and treatment of lupus. Human patients and murine models of lupus manifest a wide range of immunological abnormalities. The most pervasive of these are: (1) the ability to produce pathogenic autoantibodies; (2) lack of T- and B-lymphocyte regulation; and (3) defective clearance of autoantigens and immune complexes. This article briefly reviews immunological abnormalities and disease mechanisms characteristic of lupus autoimmunity and highlight recent studies on the use of gene therapy to target these abnormalities.
Mageed
R A
RA
Department of Immunology and Molecular Pathology, Royal Free and University College School of Medicine, London, UK.
Prud'homme
G J
GJ
D000069594:Abatacept; D000818:Animals; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D003165:Complement System Proteins / Q000172:deficiency; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D016212:Transforming Growth Factor beta; D000069594:Abatacept; D003165:Complement System Proteins