The genetic etiology of systemic lupus erythematosus: a short dispatch from the combat zone

Harley, John B.

doi:10.1038/sj.gene.6363908

Cited by 10 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For lupus, at least five linkages have been established and confirmed near 1q23, 2q37, 4p16, 6p21, and 16q13, along with many others that have yet produced such convincing results [65,66]. Of these, convincing associations are published with alleles at FcγRIIIA (1q23) [67], and PDCD1 (2q37) [68•] and HLA-DR (6q21) [69].…”

Section: Lupus and Sjögren's Syndromementioning

confidence: 89%

The genetics of primary Sjögren’s syndrome

Sawalha¹,

Potts²,

Schmid³

et al. 2003

Curr Rheumatol Rep

View full text Add to dashboard Cite

Primary Sjögren's syndrome is an autoimmune disease characterized clinically by dryness of the eyes and mouth. The use of different classification criteria for primary Sjögren's syndrome has led to dramatically different estimates of prevalence and incidence. Despite this, several genetic and environmental factors are thought to play a role in the susceptibility to primary Sjögren's syndrome, as is the current conceptual formulation of the pathogenesis of many other autoimmune maladies. Primary Sjögren's syndrome appears a complicated polygenic disorder with many genes interacting with environmental factors. Similar to many other polygenic autoimmune rheumatic diseases, human leukocyte antigen associations have been reported and confirmed. Additionally, other non-human leukocyte antigen candidate genes have been reported to reveal association with primary Sjögren's syndrome, but, in general, these effects are not confirmed. The authors review the human leukocyte antigen and non-human leukocyte antigen genetic associations herewith, knowing that new technologies are providing access to the entire genome for association studies. No doubt a much more comprehensive description of the genetics of this disorder will soon emerge.

show abstract

Section: Lupus and Sjögren's Syndromementioning

confidence: 89%

The genetics of primary Sjögren’s syndrome

Sawalha¹,

Potts²,

Schmid³

et al. 2003

Curr Rheumatol Rep

View full text Add to dashboard Cite

show abstract

“…Signi¢cant gender di¡erences are observed in prevalence, age at onset, premorbid conditions, clinical expression, course of illness, response to treatment, and morbid risk. In addition, there are important racial di¡erences in disease manifestations Harley, 2002). Clearly, SLE is a heterogeneous and complex genetic disease.…”

mentioning

confidence: 99%

“…This astonishing variation might be explained by the inheritance of di¡erent combinations of susceptibility genes, possibly in combination with di¡er-ent environmental factors. Evidence for a genetic basis is established through signi¢cant familial aggregation with 7%1 2% increased risk among the ¢rst-or second-degree relatives of a proband (Vyse and Todd, 1996), an increased concordance rate in identical twins (15^69%) as opposed to dizygotic twins (2%^5%) (Deapen et al, 1992), and genome scans showing moderate support for genetic linkage in a number of genomic locations (Ga¡ney et al, 1998;Moser et al, 1998;Shai et al, 1999;Ga¡ney et al, 2000;Gray-McGuire et al, 2000;Magnusson et al, 2000;Kelly et al, 2002;Lindqvist et al, 2002;Harley 2002). The relative risk ratio for the siblings of an a¡ected proband (l s ) varies from 20 to 40 (Wandstrat, 2001).…”

mentioning

confidence: 99%

A Candidate Region on 11p13 for Systemic Lupus Erythematosus: A Linkage Identified in African-American Families

Nath

Namjou

Kilpatrick

et al. 2004

Journal of Investigative Dermatology Symposium Proceedings

View full text Add to dashboard Cite

Systemic Lupus Erythematosus (SLE), a chronic, complex disease, is the prototype for systemic human autoimmune diseases. Although environmental factors are crucial in triggering the condition, twin and family studies, as well as genetic linkage and association studies, have established its strong genetic predisposition. During the past few years, there has been considerable interest in identifying genomic segments linked to SLE through either a whole genome scan or a candidate gene approach. The discoid lupus erythematosus (DLE) skin lesion is one of the major, and discriminating, manifestations in SLE, especially in African American patients. In this study we have identified 58 multiplex families--27 African American, 26 European American, and 5 others--where at least one SLE patient is also reported to be afflicted with DLE. These families were chosen from the collection of families that are part of our ongoing linkage study for SLE. A genome-wide parametric and nonparametric linkage analysis was conducted with 320 markers. Significant evidence of linkage was identified in only one chromosomal location, 11p13, in the African American families. The maximum 2-point linkage was 5.6 in these pedigrees, obtained at a marker located 47 CM away from the pterminal end of chromosome 11. The peak multipoint LOD score of 4.6 was obtained very nearby. The segregation of this gene suggests dominant inheritance. These results reveal an important genetic effect related to discoid rash at 11p13 in African Americans with SLE, and demonstrate, through increasing genetic homogeneity, the power of pedigree stratification to detect linkage in complex diseases.

show abstract

“…Most interestingly, there are reports that polymorphisms of CTLA‐4 [89–91] and PD‐1 [92] are associated with disease in SLE patients. The genetic intervals to which these genes map, 2q33 for CTLA‐4 [93–95] and 2q37 for PD‐1 [96, 97], also locate to regions of linkage with SLE from genome‐wide scans.…”

Section: T‐helper Cell Tolerance To Non‐nuclear Antigensmentioning

confidence: 99%

T‐Helper Cell Tolerance to Ubiquitous Nuclear Antigens

et al. 2003

View full text Add to dashboard Cite

Systemic autoimmune diseases are characterized by the development of antinuclear autoantibodies. In order to understand the immunologic events leading to the development of such antibodies, knowledge of mechanisms of immune tolerance to nuclear antigens is required. By utilizing adoptive T-cell transfer strategies with transgenic mouse models expressing nuclear neo-self antigens, T-cell tolerance to the lupus-related nuclear antigens human La and nRNP A has been demonstrated. These findings also indicate the existence in normal animals of autoreactive B cells continuously presenting nuclear antigen, suggesting that nuclear antigens are not sequestered from the immune system. Investigations of CD4 þ T-cell tolerance to non-nuclear antigens have revealed a number of mechanisms that protect the host from autoreactivity, including autoreactive T-cell deletion, regulatory T-cell development and anergy induction. Recent studies using T-cell receptor and neo-self nuclear antigen transgenic mice are revealing the importance of such mechanisms in maintaining tolerance to nuclear antigens. Mechanisms of tolerogenic antigen presentation, identification of tolerogenic antigen source(s) and the pathways leading to loss of tolerance to nuclear antigens in systemic autoimmune disease states are currently being sought.

show abstract

The genetic etiology of systemic lupus erythematosus: a short dispatch from the combat zone

Cited by 10 publications

References 31 publications

The genetics of primary Sjögren’s syndrome

The genetics of primary Sjögren’s syndrome

A Candidate Region on 11p13 for Systemic Lupus Erythematosus: A Linkage Identified in African-American Families

T‐Helper Cell Tolerance to Ubiquitous Nuclear Antigens

Contact Info

Product

Resources

About