The cause of systemic lupus erythematosus: implication of ‘self-organized criticality theory of autoimmunity’ on the pathogenesis of systemic lupus erythematosus

2010 ◽  
Vol 5 (6) ◽  
pp. 619-626 ◽  
Author(s):  
Shunichi Shiozawa
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Self Organized ◽  
Self Organized Criticality

scholarly journals A Newly Generated DOCK8-expressing T Follicular Helper Cell Type, aiCD4 T Cell, Causes Systemic Lupus Erythematosus: Self-Organized Criticality Theory

2020 ◽  
Author(s):  
Shunichi Shiozawa ◽  
Ken Tsumiyama ◽  
Keiichi Sakurai ◽  
Takahiko Horiuchi ◽  
Tsukasa Matsubara ◽  
...  
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Cd4 T Cells ◽  
Cell Type ◽  
Systemic Lupus ◽  
Self Organized ◽  
Follicular Helper ◽  
Helper Cell Type ◽  
Self Organized Criticality ◽  
T Follicular Helper Cell

Abstract Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease of unknown cause. We show here that a novel T follicular helper cell type expressing the guanine nucleotide exchange factor DOCK8 on the cell surface causes SLE. These cells, which we have designated autoantibody-inducing CD4 T (aiCD4 T) cells, are generated after resuscitation from anergy following strong TCR stimulation by antigen. When mice normally not prone to autoimmune disease were repeatedly immunized with an antigen such as OVA, they generated DOCK8+ CD4 T cells. These DOCK8+ CD4 T cells, in vivo and also upon transfer to naïve mice, induced a variety of autoantibodies and lesions characteristic of SLE. TCR repertoire analyses showed that a substantial number of novel TCR repertoires were generated in the DOCK8+ CD4 T cells, which induced novel autoantibodies upon transfer to naïve mice. DOCK8+ CD4 T cells are localized in splenic red pulp, the space immunoreactive against a variety of antigens, and specifically increased in the peripheral blood of SLE patients in association with disease activity. Anti-DOCK8 antibody treatment ameliorated the lesions induced by DOCK8+ CD4 T cells and in lupus model (NZB x W) F1 mice. Thus, when CD4 T cells are overstimulated by an external disturbance, i.e., repeatedly stimulated with antigen, to levels that surpass the system’s self-organized criticality, these cells express DOCK8 on the cell surface and acquire autoreactivity via TCR re-revision at the periphery. These DOCK8+ CD4 T cells subsequently induce a variety of autoantibodies and 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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