Molecular aspects in the pathogenesis of human systemic lupus erythematosus.
Systemic lupus erythematosus is a common and often devastating systemic autoimmune disease of unknown etiology. In this communication we review the latest developments of the molecular pathogenesis of human lupus. Novel genetic studies of multiplex lupus families have revealed potential disease-associated genome intervals, put special emphasis on genetic loci mapping in the long arm of chromosome 1 and have underscored the complexity of the underlying genetic background. New data have emerged on the role of estrogens in the function of lymphocytes and a number of studies have recently emphasized the relative Th-1/Th-2 cytokine imbalance in favor of a Th-2 type cytokine immune response. Finally, novel experiments have revealed an abnormal antigen receptor-mediated signaling process in lupus T and B cells, which may influence the aberrant expression and function of costimulatory molecules as well as of other aspects of immune cell function. It is important to decipher the underlying molecular mechanisms that govern the expression of human lupus, because we may design novel, rational approaches in the treatment of a human lupus, a disease that has high morbidity and mortality.
Liossis
S N
SN
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Tsokos
G C
GC
D000974:Antibodies, Antinuclear / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D004777:Environment; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D012307:Risk Factors; D015398:Signal Transduction
D000974:Antibodies, Antinuclear; D016207:Cytokines; D012739:Gonadal Steroid Hormones