Genetic studies of systemic lupus erythematosus

Understanding the pathogenesis of systemic lupus erythematosus (SLE) remains a considerable challenge. Multiple abnormalities of both the innate and adaptive immune system have been described and, furthermore, immunological dysfunction precedes clinical presentation by many years. There is a strong genetic basis to SLE, which means that genetic studies can play a key role in furthering our understanding of this disease. Because susceptibility variants are present from birth and are unaffected by the course of the disease, or by its treatment, genetic analysis is, perhaps uniquely, capable of identifying fundamental, causative, disease mechanisms. In this article, we review our SLE immunogenetic studies performed in collaboration with the European Working Party on Systemic Lupus Erythematosus. By considering the results of our research and the recent advances obtained by genome-wide associations’ studies, we can begin to understand how dysregulation at a number of key immunological steps may predispose to the development of SLE.

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Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/273907 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 18

Author(s):

Theophanis P. Karageorgas ◽

Dimitrios D. Tseronis ◽

Clio P. Mavragani

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Type I Interferon ◽

Clinical Manifestations ◽

Type I ◽

Type I Ifn ◽

Systemic Lupus ◽

Genetic Studies ◽

Interferon Pathway

Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target.

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Organized Intraglomerular Deposits in NZB Mouse Disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066772 ◽

1971 ◽

Vol 29 ◽

pp. 544-545

Author(s):

Francis R. Comerford ◽

Alan S. Cohen

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antinuclear Antibodies ◽

Human Systemic Lupus Erythematosus ◽

Systemic Lupus ◽

Glomerular Lesion ◽

Ultrastructural Studies ◽

Dense Deposits ◽

Experimental Nephritis ◽

Glomerular Lesions

Mice of the inbred NZB strain develop a spontaneous disease characterized by autoimmune hemolytic anemia, positive lupus erythematosus cell tests and antinuclear antibodies and nephritis. This disease is analogous to human systemic lupus erythematosus. In ultrastructural studies of the glomerular lesion in NZB mice, intraglomerular dense deposits in mesangial, subepithelial and subendothelial locations were described. In common with the findings in many examples of human and experimental nephritis, including many cases of human lupus nephritis, these deposits were amorphous or slightly granular in appearance with no definable substructure.We have recently observed structured deposits in the glomeruli of NZB mice. They were uncommon and were found in older animals with severe glomerular lesions by morphologic criteria. They were seen most commonly as extracellular elements in subendothelial and mesangial regions. The deposits ranged up to 3 microns in greatest dimension and were often adjacent to deposits of lipid-like round particles of 30 to 250 millimicrons in diameter and with amorphous dense deposits.

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“Subcortical” cognitive impairment in patients with systemic lupus erythematosus

Journal of the International Neuropsychological Society ◽

10.1017/s1355617700677093 ◽

2000 ◽

Vol 6 (7) ◽

pp. 821-825 ◽

Cited By ~ 29

Author(s):

ELIZABETH LERITZ ◽

JASON BRANDT ◽

MELISSA MINOR ◽

FRANCES REIS-JENSEN ◽

MICHELLE PETRI

Keyword(s):

Systemic Lupus Erythematosus ◽

Cognitive Impairment ◽

Lupus Erythematosus ◽

Systemic Lupus

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