Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus

2011 ◽  
Vol 43 (12) ◽  
pp. 1186-1188 ◽  
Author(s):  
Sulaiman M Al-Mayouf ◽  
Asma Sunker ◽  
Reem Abdwani ◽  
Safiya Al Abrawi ◽  
Fathiya Almurshedi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Loss Of Function ◽  
Systemic Lupus ◽  
Familial Form

scholarly journals HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Mudan Lu ◽  
Shanshan Yu ◽  
Wei Xu ◽  
Bo Gao ◽  
Sidong Xiong
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Function Analysis ◽  
Critical Role ◽  
Loss Of Function ◽  
Systemic Lupus ◽  
Glycation End Products ◽  
Hmgb1 Expression

Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE); however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure.Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues.Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-αand IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response.Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.

scholarly journals A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus

2008 ◽  
Vol 18 (3) ◽  
pp. 569-579 ◽  
Author(s):  
V. Orru ◽  
S. J. Tsai ◽  
B. Rueda ◽  
E. Fiorillo ◽  
S. M. Stanford ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Loss Of Function ◽  
Systemic Lupus ◽  
Reduced Risk

Thrombocytopenia identifies a severe familial phenotype of systemic lupus erythematosus and reveals genetic linkages at 1q22 and 11p13

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 992-997 ◽  
Author(s):  
R. Hal Scofield ◽  
Gail R. Bruner ◽  
Jennifer A. Kelly ◽  
Jeff Kilpatrick ◽  
Debra Bacino ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Genetic Risk ◽  
Severe Disease ◽  
Antiphospholipid Antibody ◽  
Severe Phenotype ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Familial Form ◽  
Genetic Linkages

Abstract Systemic lupus erythematosus (SLE) is a complicated autoimmune disease with a definite genetic predisposition. Thrombocytopenia predicts severe disease and death in SLE, making the identification of the related genetic risk factors especially important. We selected the 38 pedigrees that had an SLE patient with thrombocytopenia (platelets, < 10 × 109/L [< 100 000/μL]) from a collection of 184 pedigrees multiplex for SLE. Linkages were established at 1q22-23 (maximum logarithm of odds [lodmax] = 3.71) in the 38 pedigrees and at 11p13 (lodmax = 5.72) in the 13 African American pedigrees. Nephritis, serositis, neuropsychiatric involvement, autoimmune hemolytic anemia, anti–double-stranded DNA, and antiphospholipid antibody were associated with thrombocytopenia. Other results show that SLE is more severe in the families with a thrombocytopenic SLE patient, whether or not thrombocytopenia in an individual patient is considered. These results are consistent with thrombocytopenia being a component of a severe familial form of SLE and with genes at 1q22-23 and 11p13 contributing to this severe phenotype and to the subsequent high mortality associated with thrombocytopenia in SLE.

Organized Intraglomerular Deposits in NZB Mouse Disease

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.

“Subcortical” cognitive impairment in patients with systemic lupus erythematosus

2000 ◽  
Vol 6 (7) ◽  
pp. 821-825 ◽  
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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