Gene/Protein
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Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0024141 (
systemic lupus erythematosus
)
44,322
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Programmed cell death 1
(
PD-1
) was isolated in 1992 by subtractive-hybridization technique, as a molecule whose expression is enhanced by apoptotic stimuli. Since then we have been analyzing the function of
PD-1
in the regulation of immune responses. Generation of
PD-1
deficient mice, pathophysiological analyses of autoimmune diseases in
PD-1
deficient mice, identification of two ligands, and analyses of downstream events of
PD-1
revealed that
PD-1
prevents autoimmunity by inhibiting activation of self-reactive lymphocytes. These findings were further applied on human autoimmune diseases and single nucleotide polymorphisms (SNPs) on human
PD-1
gene have been reported to link with
systemic lupus erythematosus
(
SLE
), rheumatoid arthritis (RA) and type I diabetes.
...
PMID:PD-1/PD-L pathway and autoimmunity. 1622 50
Programmed cell death 1
(PDCD1 or PD1) polymorphisms have been inconsistently reported to be associated with
systemic lupus erythematosus
(
SLE
). The aim of this study was to explore whether the PDCD1 polymorphisms confer a susceptibility to
SLE
and lupus nephritis (LN). We conducted a meta-analysis on the association of PDCD1 polymorphisms with
SLE
in overall and specific ethnic populations. A total of 15 separate comparisons were included in this meta-analysis consisting of nine Europeans, two Latin Americans, two Africans, one Asian and one unknown participant. In subgroup analysis, the PD1.3A allele was significantly associated with
SLE
in Latin Americans (OR = 3.073, 95% CI = 1.416-6.461, P = 0.003), but not in patients of European and African decent. The PD1.3A allele was a risk factor for LN in European descendants (OR = 2.207, 95% CI = 1.488-3.467, P < 0.001). The PD1.5C allele was a risk factor for
SLE
in Europeans (OR = 1.297, 95% CI = 1.024-1.643, P = 0.031). In conclusion, this meta-analysis demonstrated an association of the PD1.3A allele with LN in European and
SLE
in Latin-American populations. Furthermore, the PD1.5C allele was associated with
SLE
susceptibility in Europeans.
Lupus
2009 Jan
PMID:Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. 1907 63
Programmed cell death 1
(
PD-1
) is an immunosuppressive receptor that transduces an inhibitory signal into activated T cells. Although a single nucleotide polymorphism in the gene for
PD-1
is associated with susceptibility to
systemic lupus erythematosus
, the role of
PD-1
in
systemic lupus erythematosus
is still not well understood. In this study, we used NZB/W F1 mice, a model of
lupus
-like nephritis, to examine the function of
PD-1
and its ligands.
PD-1
was predominantly expressed on CD4(+) T cells that infiltrated the kidney, and CD4(+)
PD-1
(high) T cells produced higher levels of IFN-gamma than CD4(+)
PD-1
(low) or CD4(+)
PD-1
(-) T cells. Stimulation with PMA/ionomycin caused splenic CD4(+)
PD-1
(+) T cells to secrete high levels of IFN-gamma, IL-10, low levels of TNF-alpha, faint levels of IL-2, IL-21, and no IL-4, IL-17. In vivo anti-
PD-1
mAb treatment reduced the number of CD4(+)
PD-1
(+) T cells in the kidney of NZB/W F1 mice and significantly reduced their mortality rate (p = 0.03). Conversely, blocking PD-L1 using an anti-PD-L1 mAb increased the number of CD4(+)
PD-1
(+) T cells in the kidney, enhanced serum IFN-gamma, IL-10, and IgG2a ds-DNA-Ab levels, accelerated the nephritis, and increased the mortality rate. We conclude that CD4(+)
PD-1
(high) T cells are dysregulated IFN-gamma-producing, proinflammatory cells in NZB/W F1 mice.
...
PMID:Anti-programmed cell death 1 antibody reduces CD4+PD-1+ T cells and relieves the lupus-like nephritis of NZB/W F1 mice. 2013 71
