While patients with anti-RNP precipitin showed an increased frequency of the DQw8-associated allele DQB1*0302 (P = 0.02, OR = 3.7) compared with normal controls, as well as an increased frequency of the DQw5-associated alleles DQA1*0101 and DQB1*0501 (P = 0.05, OR = 4.2) compared with lupus patients without anti-Sm or RNP.
We demonstrate herein that the accelerated development of lupus-like autoimmune disease in MRL-lpr/lpr and MRL.Yaa mice, as compared with MRL-lpr/lpr.ll and MRL-+/+ mice, respectively, was correlated with an enhanced expression of IFN-gamma vs IL-4 and IL-10 mRNA in CD4+ T cells, which paralleled with an increase of spontaneous and foreign T cell-dependent antigen-induced productions of IgG2a and IgG3 vs IgG1 antibodies.
Anti-CD40 ligand antibody treatment prevents the development of lupus-like nephritis in a subset of New Zealand black x New Zealand white mice. Response correlates with the absence of an anti-antibody response.
We demonstrate herein that the accelerated development of lupus-like autoimmune disease in MRL-lpr/lpr and MRL.Yaa mice, as compared with MRL-lpr/lpr.ll and MRL-+/+ mice, respectively, was correlated with an enhanced expression of IFN-gamma vs IL-4 and IL-10 mRNA in CD4+ T cells, which paralleled with an increase of spontaneous and foreign T cell-dependent antigen-induced productions of IgG2a and IgG3 vs IgG1 antibodies.
To investigate the respective roles of Th1 and Th2 cells in the pathogenesis of lupus-like autoimmune disease, we have analyzed the spontaneous and antigen-induced productions of IgG1 vs IgG2a and IgG3 subclasses in relation to the mRNA expression of INF-gamma (Th1 cytokine promoting IgG2a and IgG3 production), IL-4 (Th2 cytokine promoting IgG1 production), and IL-10 (Th2 cytokine) in CD4+ T cells from lupus-prone MRL mice.
We demonstrate herein that the accelerated development of lupus-like autoimmune disease in MRL-lpr/lpr and MRL.Yaa mice, as compared with MRL-lpr/lpr.ll and MRL-+/+ mice, respectively, was correlated with an enhanced expression of IFN-gamma vs IL-4 and IL-10 mRNA in CD4+ T cells, which paralleled with an increase of spontaneous and foreign T cell-dependent antigen-induced productions of IgG2a and IgG3 vs IgG1 antibodies.
These results show that p36 is a new interferon-alpha-induced protein that localizes in the endoplasmic reticulum, the cell region in which the lupus inclusions form, and that p36 is probably physically associated with the lupus inclusions.
These results show that p36 is a new interferon-alpha-induced protein that localizes in the endoplasmic reticulum, the cell region in which the lupus inclusions form, and that p36 is probably physically associated with the lupus inclusions.
These results show that p36 is a new interferon-alpha-induced protein that localizes in the endoplasmic reticulum, the cell region in which the lupus inclusions form, and that p36 is probably physically associated with the lupus inclusions.
The 16-mer Ki peptide containing the sequence homologous to the SV40 T NLS is one of the antigenic epitopes recognized by anti-Ki antibodies in lupus sera.
These results show that p36 is a new interferon-alpha-induced protein that localizes in the endoplasmic reticulum, the cell region in which the lupus inclusions form, and that p36 is probably physically associated with the lupus inclusions.
The analysis of the beta chain of the TCR revealed little clonotypic T cell expansion in the peripheral blood of lupus patients in remission, whereas in patients with active disease many dominant T cell clonal expansions without any distinct V beta bias were observed.
This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants.
Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein.
Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein.
Universally binding nucleosomal epitopes are productively recognized by autoreactive T cells by binding to the T-cell receptor-alpha chain; (b) circulating T cells from patients with lupus commonly display a deficiency of the T-cell receptor zeta chain, and upon ligation of their cell-surface antigen receptor overproduce tyrosine phosphorylated proteins; (c) lupus and lupus nephritis are associated with a low-binding FcgammaRIIIA (CD16) polymorphism that crosses ethnic barriers; (d) the pathogenetic role of the cytokine interleukin-10 is expanding, because it is reportedly overproduced not only by cells from lupus patients but also by cells from their healthy relatives, and its overproduction in vitro is correlated with increased apoptotic cell death and with lymphopenia.
Peripheral blood T cells and monocytes and B cell lines derived from patients with lupus express estrogen receptor transcripts similar to those of normal cells.
But patients with SLE had significantly increased percentages of CTLA-4-positive T cells compared with normal controls, implying at least that there was no apparent defective expression of CTLA-4 molecule in human lupus.
The lupusTCR-alpha chains probably contact the nucleosomal peptide complexed with MHC with relatively high affinity/avidity to sustain TCR signaling, because CD4 coreceptor was not required for promiscuous recognition.
Universally binding nucleosomal epitopes are productively recognized by autoreactive T cells by binding to the T-cell receptor-alpha chain; (b) circulating T cells from patients with lupus commonly display a deficiency of the T-cell receptor zeta chain, and upon ligation of their cell-surface antigen receptor overproduce tyrosine phosphorylated proteins; (c) lupus and lupus nephritis are associated with a low-binding FcgammaRIIIA (CD16) polymorphism that crosses ethnic barriers; (d) the pathogenetic role of the cytokine interleukin-10 is expanding, because it is reportedly overproduced not only by cells from lupus patients but also by cells from their healthy relatives, and its overproduction in vitro is correlated with increased apoptotic cell death and with lymphopenia.
The induction of PAI-1 and TF, and the decrease in u-PA expression in the kidneys of lupus-prone or of endotoxemic mice may promote the formation of renal microthrombi and thus contribute to the progression of renal damage in these models.
Immunoperoxidase studies on kidney biopsies showed COX-1 staining in glomerular arterioles and other renal vessels, with no evident difference between lupus biopsies and control specimens taken from either individuals who were free of renal disease or patients with non-lupus nephropathies.