Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A naturally occurring T-lymphocytotoxic autoantibody (Hu-NTA) in serum from a patient with systemic lupus erythematosus (SLE) showed a differential cytotoxic effect on functionally different T cell subsets as did natural thymocytotoxic autoantibody (NTA) of NZB mice. When the normal peripheral blood lymphocytes were treated, in the presence of complement, with Hu-NTA at a dilution that eliminated 25 to 30% of Hu-NTA-sensitive T cells, there was a marked reduction or a total depletion in the ability of resultant cells to show Con A-activated suppression on the proliferative response of responder cells in mixed lymphocyte reaction. The treatment of PBL in the same manner also resulted in a marked reduction in its responsiveness to Con A and PHA. However, the responder cells to allogeneic stimulator cells in MLR were found to be much more resistant to the cytotoxicity of Hu-NTA than other functional T cell subsets tested. These results suggest that Hu-NTA is responsible for the selective loss of certain functional T cell subsets including suppressor T cells in patients with SLE.
Arthritis Rheum 1979 Feb
PMID:Differential sensitivity of functional subsets of T cells to the cytotoxicity of natural T-lymphocytotoxic autoantibody of systemic lupus erythematosus. 15 30

Autoantibodies directed against a ribosomal small subunit protein of 20,000 molecular weight were found in sera from 5 of 44 patients with systemic lupus erythematosus (11%) and 5 of 48 MRL/lpr mice (10%). This ribosomal protein was identified as S10 on the basis of two-dimensional gel electrophoresis and immunoblotting, as well as immunoblots of the purified S10 protein. The S10 protein antigen was readily extracted from ribosomes at low salt (300 mM KCl) and low magnesium (0.5 mM) concentrations, consistent with the highly exposed location proposed for this protein on the 40S subunit. Anti-S10 antibodies were observed significantly more frequently in lupus sera containing both anti-Sm and antiribosomal P protein antibodies and in MRL/lpr sera with anti-Sm activity, suggesting a linked pattern of autoantibody response. Together with anti-Sm and antiribosomal P protein antibodies, anti-S10 represents a third autoantibody highly specific for lupus in humans and MLR/lpr mice.
Arthritis Rheum 1989 Oct
PMID:Antiribosomal S10 antibodies in humans and MRL/lpr mice with systemic lupus erythematosus. 247 35

Spirogermanium (SG) is a metal-containing compound reported to have antitumor, antiarthritic, antimalarial and immunoregulatory activity. In this study we have demonstrated that treatment of mice and rats with spirogermanium results in an inhibition of autoimmune disease and cell-mediated immune (CMI) responses. Prophylactic administration of SG inhibited the development of adjuvant-induced arthritis and the DTH response to purified protein derivative (PPD) in Lewis strain rats. SG treatment was also able to alleviate the symptoms of experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats. In two strains of mice, BDF1 and C57B1/6, the DTH response to sheep red blood cells could be suppressed by intraperitoneal (i.p.) administration of SG. The spleens of both mice and rats that have been treated with this drug contain suppressor cells which inhibit the response of normal cells to concanavalin A (Con A) and the mixed lymphocyte reaction. In addition, the generation of cytotoxic T cells (CTL) in the murine MLR is abrogated in the presence of these suppressor cells. The suppressor cells were radiation-resistant (2000 rad), indomethacin-insensitive and were not depleted by treatment with anti-Thy-1.2 antiserum plus complement. These results suggest that SG modulates cell-mediated immune responses in vivo by the induction of non-specific suppressor cells.
 ...
PMID:Immunomodulatory activity and non-specific suppressor cell generation by spirogermanium in murine and rat models of cell-mediated immunity. 297 35

In summary, the work reviewed in the present paper indicates that 1. Iron and the iron-binding proteins can act as regulators of immune function, and not only as a result of a nutritional dependence of lymphoid cells on transferrin and transferrin-iron. Subsets of cells of the immune system respond differently to increases in iron concentration in vitro and in vivo. 2. Macrophages and lymphocytes differ in the H and L subunit content of the ferritins synthesized in response to increases in iron concentration in vitro. 3. NK activity by adherent and nonadherent cells differ in their susceptibility to the enhancing effect of lactoferrin in vitro. 4. Responses to mitogen stimulation by PHA and Con A are diminished, while the PWM response remains unaffected by exposure to acidic ferritins or by increasing concentrations of iron in vitro and in vivo. 5. Pretreatment of effector but not target cells with iron results in diminished responses in the MLR, an effect that appears to be related to the HLA-A locus. 6. In situ hybridization studies indicate that transferrin is synthesized by a specific subset of the T lymphocytes. 7. Transient increases in serum iron concentration above the full saturation of transferrin, reproducing the clinical situation frequently seen in hereditary hemochromatosis, are followed by a series of cellular changes in the synovium that can be correlated to changes in the course of an experimental model of arthritis in the rat.
 ...
PMID:Iron, iron-binding proteins and immune system cells. 329 85

Purified T cells from normal subjects and patients with systemic lupus erythematosus (SLE) were studied for their abilities to respond to hapten modified self antigens and to antigens on autologous non T cells. Primary and secondary proliferative T cell responses to trinitrophenyl modified (TNP) non T cells were markedly impaired in patients with active SLE as compared with normal subjects or patients with inactive SLE. In contrast, patients with active SLE had significantly stronger cytotoxic activity against TNP modified autologous non T cells. Patients with active SLE had impaired proliferative responses to nonmodified autologous non T cells (auto-MLR). A significant negative correlation was observed between the degree of the auto-MLR and the degree of cytotoxic ability against TNP modified autologous cells in patients with SLE. This observation suggests that cells capable of proliferating in the auto-MLR might regulate the generation of cytotoxic T cell responses against modified self. We then analyzed the ability of anti T cell antibodies from patients with active SLE to preferentially interfere with this naturally occurring suppressor T cell function.
Arthritis Rheum 1982 Jul
PMID:Immune responses to hapten-modified self and their regulation in normal individuals and patients with systemic lupus erythematosus. 621 39

Lewis rats develop immune-mediated arthritis following injection with a variety of agents including bovine type II collagen (bCII), mycobacteria, muramyl dipeptide and CP20961. Since susceptibility to experimentally-induced arthritis has been linked to the genes encoding the major histocompatibility complex, it is hypothesized that antigen presentation to autoreactive T-cells is a critical event in the pathogenesis of disease. T-cells, isolated from Lewis rats immunized with bCII or mycobacteria, were co-cultured with splenic or thymic antigen presenting cells (APC) and proliferative responses to antigen were assessed by 3H-thymidine incorporation. T-cell proliferation was observed upon culture with APC without requiring the addition of antigen. T-cells from rats injected with non-immunogenic adjuvants also demonstrated an increased autologous MLR compared to T-cells from non-injected animals. In contrast, T-cells from animals immunized with non-arthritogenic antigens, including ovalbumin or tetanus toxoid, proliferated only when co-cultured with specific antigen-pulsed APC. These results suggest that immunization with arthritogens activates a population of self-reactive T-cells, which respond in an autologous MLR. We propose that these autoreactive T-cells recognize endogenously-derived self peptides rather than peptides derived from a joint autoantigen.
 ...
PMID:Autologous mixed lymphocyte responses in experimentally-induced arthritis of the Lewis rat. 1207 34

Collagen-induced arthritis (CIA) is a chronic inflammatory arthropathy of rats which follows immunization with bovine type II collagen (bCII). T cell lines generated from arthritic rats have been shown to be self-reactive and proliferate in an autologous MLR, which is MHC-dependent. However, the peptides which drive this autoreactive response remain to be elucidated. T cell lines, generated initially to bCII, were cultured with synthetic peptides representing potential autoreactive self epitopes. C1q-c(50-64) peptide, which demonstrates sequence homology to the bCII(184-198) peptide, failed to stimulate T cell proliferation suggesting that the autologous MLR was not due to antigen cross-reactivity with this self peptide. In contrast, several peptides from the amino-terminal region of the RT1D(u) MHC class II molecule stimulated proliferative responses. These results suggest that immunization with bCII leads to activation of a population of autoreactive T cells which respond in an autologous MLR, and that this response could be due, in part, to T cell reactivity to self MHC peptides.
 ...
PMID:Autoreactivity in collagen-induced arthritis of rats: a potential role for T cell responses to self MHC peptides. 1214 8

Systemic lupus erythematosus is a complement-mediated autoimmune disease. While genetic deficiencies of classical pathway components lead to an increased risk of developing systemic lupus erythematosus, end organ damage is associated with complement activation and immune complex deposition. The role of classical pathway regulators in systemic lupus erythematosus is unknown. C4 binding protein (C4bp) is a major negative regulator of the classical pathway. In order to study the role of C4bp deficiency in an established murine model of lupus nephritis, mice with a targeted deletion in the gene encoding C4bp were backcrossed into the MRL/lpr genetic background. Compared with control MRL/lpr mice, C4bp knockout MLR/lpr mice had similar mortality and similar degrees of lymphoproliferation. There were no differences in the extent of proteinuria or renal inflammation. Staining for complement proteins and immunoglobulins in the kidneys of diseased mice revealed no significant strain differences. Moreover, there was no difference in autoantibody production or in levels of circulating immune complexes. In comparison with C57BL/6 mice, MRL/lpr mice had depressed C4 levels as early as 3 weeks of age. The absence of C4bp did not impact serum C4 levels or alter classical pathway hemolytic activity. Given that immune complex renal injury in the MRL/lpr mouse is independent of Fc receptors as well as the major negative regulator of the classical pathway, new mechanisms for immune-complex-mediated renal injury need to be considered.
Arthritis Res Ther 2007
PMID:Analysis of C4 and the C4 binding protein in the MRL/lpr mouse. 1830 82

We have developed a new series of immunosuppressant with improved pharmacokinetic properties as the second-generation of colchicine analogs, which were designed based on the privileged structure derived from our previous work. In particular, we identified an analog (14), which exhibited a potent in vitro activity (IC(50): 5 nM) in MLR and excellent in vivo efficacy in the Zymosan A-induced arthritis model, in the Carrageenan-induced edema model and in the local lymph node assay (LLNA). Analog 14 also revealed a good oral bioavailability (F: 67.3%) in BALB/c mice.
 ...
PMID:Part II. Development of novel colchicine-derived immunosuppressants with improved pharmacokinetic properties. 2301 85

Siglec-G is a member of the sialic acid-binding Ig-like lectin (Siglec) family expressed on all B cells. Siglec-G-deficient mice show a large expansion of the B1 cell compartment, demonstrating the crucial role of Siglec-G as an inhibitory receptor on this cellular subset. Although Siglec-G-deficient mice did not develop spontaneous autoimmunity, mice double-deficient for Siglec-G and the related Siglec protein CD22 did show autoimmunity at an older age. In this study, we addressed the question of whether loss of Siglec G on its own affects disease severity in animal models of rheumatoid arthritis and systemic lupus erythematosus. Siglec-G-deficient mice showed moderately increased clinical severity and higher inflammation of the knee joints following collagen-induced arthritis, when compared with control mice. The Siglec-G-deficient mouse was also backcrossed to the autoimmune prone MLR/lpr background. Although both Siglec-G-deficient and control MRL/lpr mice developed a lupus-like disease, Siglec-G-deficient MRL/lpr mice showed an earlier occurrence of autoantibodies; a higher lymphoproliferation of B and T cells; and an earlier onset of disease, as shown by proteinuria and glomerular damage in the kidney. Moreover, Siglec-G-deficient female mice showed a significantly reduced survival compared with female control MRL/lpr mice. Thus, the loss of the inhibitory receptor Siglec-G led to a moderate exacerbation of disease severity and early onset in both collagen-induced arthritis and spontaneous lupus nephritis in MRL/lpr mice.
...
PMID:Siglec-G deficiency leads to more severe collagen-induced arthritis and earlier onset of lupus-like symptoms in MRL/lpr mice. 2460 33


1 2 Next >>