Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that antiphospholipid autoantibodies do not recognize phospholipid alone, but rather the plasma protein beta 2-glycoprotein I (beta 2GPI), or a beta 2GPI-phospholipid complex. In vitro beta 2GPI binds to anionic phospholipids and inhibits the prothrombinase activity of procoagulant membranes. In light of the fact that lupus anticoagulants, a type of antiphospholipid antibody, have similar anticoagulant properties, the relationship of beta 2GPI to lupus anticoagulant activity was investigated. IgG from patients with autoimmune diseases or syphilis were tested for anticardiolipin reactivity and lupus anticoagulant activity in the presence and absence of beta 2GPI. As expected, anti-cardiolipin reactivity associated with autoimmune disease was beta 2GPI dependent. In contrast, IgG from a patient with syphilis recognized cardiolipin alone and binding was inhibited by beta 2GPI. Autoimmune antiphospholipid antibodies prolonged the dilute Russell viper venom time of normal plasma, but had no effect on beta 2GPI-depleted plasma. Antiphospholipid antibodies associated with syphilis had no anticoagulant effect. RP-1, an anti-beta 2GPI mAb, had anticoagulant effects similar to those of autoimmune antiphospholipid antibodies. These data demonstrate that antiphospholipid autoantibodies exert lupus anticoagulant activity via an interaction with beta 2GPI. These antibodies and RP-1 appear to amplify the anticoagulant effect of beta 2GPI itself.
 ...
PMID:Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. 152 18

Over the last three years there has been a dramatic rise in the number of trials using monoclonal antibodies in the treatment of rheumatoid arthritis. So far, the numbers of patients treated in the individual studies have been small, and the study designs not comparable. All these trials have been conducted in a non-blinded, uncontrolled fashion. The patient populations tended to represent the severe end of the disease spectrum, being usually individuals for whom all other conventional and sometimes even unconventional experimental therapeutic approaches have failed. Clearly, therefore, larger controlled double blind studies in patients with less advanced stages of rheumatoid arthritis are needed. In the trials thus far, long-standing diseases afflicting the joints, usually with severe destruction, have frequently made clinical evaluation very difficult. Moreover, apparently with the exception of one or two reagents (16H5 and possibly B-F5) routine laboratory parameters which are helpful in determining disease activity such as CRP or the rheumatoid factor usually remain unaltered with anti-T cell therapy. In addition, in some individuals there was no clinical improvement despite sometimes severe CD4 cell depletion. The notion that the mere depletion of CD4+ cells is not sufficient to permanently suppress disease activity in autoimmune disease is further supported by studies carried out by Conolly and Wofsy in 1990. In a mouse lupus model, these investigators demonstrated that a small subpopulation of CD4+ T cells may be refractory to depletion by anti-CD4 and may be able to promote the full expression of the disease. Similar mechanisms could apply to certain individuals with human autoimmune disorders. Many additional questions remain open. The most important of these is which markers identify clinical responders to therapy. Attempts to correlate clinical response to the level of T cell depletion, modulation of the target antigens or in vitro functional assays so far have not yielded significant results. Other questions relate to the frequency of antibody administration and the amounts needed to permanently suppress disease activity. The initial hope based on animal experiments of inducing a permanent tolerance to certain antigens by anti-CD4 treatment has been clearly shown not to apply to rheumatoid arthritis. Even though there are individual variations, the efficacy of anti-T cell treatment tends to wear off after 3 or even 1 month, necessitating retreatment. Protocols will have to be designed for either longer treatment periods, repeated courses or more frequent single administrations.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Management of early inflammatory arthritis. Intervention with immunomodulatory agents: monoclonal antibody therapy. 152 46

The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.
 ...
PMID:H-2-linked control of the Yaa gene-induced acceleration of lupus-like autoimmune disease in BXSB mice. 153 72

B cell repertoire changes that characterize systemic autoimmune disease may be linked to an acceleration of normal immune aging. To examine this issue, the repertoires expressed by lupus-prone and geriatric normal mice were compared. An ELISA-spot assay was used to identify and quantitate individual lymphocytes secreting antibodies reactive with a panel of five autoantigens and three conventional Ag. Over half of autoimmune NZB and MRL/lpr mice developed repertoires biased toward the production of specific autoantibodies by 8 mo of age. The B cell repertoires expressed by normal BALB/c mice were stable over this period but developed a similar bias toward the production of autoantibodies by 18 to 22 mo of age. As both normal and autoimmune mice grew older, they expressed repertoires that increasingly diverged from those of other members of the same strain--a process whose onset and rate of development was accelerated in lupus-prone animals. By analyzing B cells from individual MRL/lpr mice at multiple time points, we found that 1) autoreactivity developed over a specific time period, 2) individual animals developed increased responsiveness against different autoantigens, and 3) this increased responsiveness persisted for life. These results suggest that the repertoires of adult autoimmune mice are generated and maintained by a process of continuous (auto)antigenic stimulation similar to that associated with normal immune aging.
 ...
PMID:Similarities in B cell repertoire development between autoimmune and aging normal mice. 153 20

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an apparent autoimmune disorder that resembles SLE. We previously showed that C1q precipitins in HUVS sera are IgG autoantibody to human C1q. We have compared HUVS anti-C1q autoantibody to a similar autoantibody in the serum of some patients with SLE. As with anti-C1q autoantibody in SLE sera, the HUVS autoantibody binds only to the collagen-like region (CLR) of C1q. In both HUVS and SLE, IgG2 is the predominant subclass of IgG autoantibody and IgM autoantibody to C1q is uncommon. In both diseases, anti-C1q autoantibodies bind preferentially to surface-adsorbed C1q or CLR fragments compared to these antigens in solution. Finally, when HUVS or SLE autoantibodies were added to CLR-coated wells already bound, respectively, by SLE or HUVS autoantibodies, no increases in CLR binding were observed, suggesting that HUVS and SLE autoantibodies to C1q bind to the same CLR epitope(s).
 ...
PMID:Comparison of autoantibodies to the collagen-like region of C1q in hypocomplementemic urticarial vasculitis syndrome and systemic lupus erythematosus. 153 23

Systemic lupus erythematosus (SLE) developed in a 10 1/2-year-old white boy with juvenile laryngeal papillomatosis who had been treated with interferon alfa-n1 for 7 years. His age, gender, and fast recovery after discontinuation of interferon therapy and institution of appropriate treatment for SLE are compatible with a diagnosis of drug-induced SLE. Autoimmune disorders may occur as a complication of interferon therapy.
 ...
PMID:Systemic lupus erythematosus in a child receiving long-term interferon therapy. 153 92

Systemic lupus erythematosus (SLE) is an autoimmune disease. Antibodies directed mainly against DNA and/or phospholipids are present in the serum of SLE patients. Therefore phosphorylated polystyrene derivatives acting as DNA-like polymers should be able to interact with the SLE anti-DNA antibodies. Such functional polymers were synthesized and subsequently their interactions with the anti-DNA antibodies studied. Adsorption experiments performed with both anti-DNA antibodies and normal immunoglobulins showed high affinity constants of the phosphorylated polymer for anti-DNA antibodies (4 x 10(9) M-1) whereas for normal IgG the affinity was low (2 x 10(5) M-1). Moreover, the interaction was specific involving the idiotypic moiety of the anti-DNA antibodies and an array of phosphoester groups at the surface of this biomaterial.
 ...
PMID:Insoluble DNA-like phosphorylated polystyrene: specific interactions with anti-DNA antibodies from systemic lupus erythematosus patients. 154 10

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by the production of autoantibodies which leads to an array of clinical symptoms. Among these autoantibodies, anti-DNA antibodies play a major role, since resulted DNA/anti-DNA immune complexes(IC) cause glomerulonephritis and other autoimmune local lesions in SLE. In this report, spectrotypes of anti-DNA antibodies of IgG, IgA and IgM classes, and IC were studied by isoelectric focusing. The size of IC was also studied. Anti-DNA autoantibodies in the sera of SLE patients were found mainly in IgG class, however, those of IgA and IgM classes were detected as minor subpopulations. By electrofocusing, both IgA and IgM anti-DNA antibodies were focused to relatively restricted acidic regions. In contrast, IgG anti-DNA antibodies were focused to two distinct pH regions; one was the acidic region similar to that IgA and IgM antibodies migrated (pH 3.2 to 6.0), and the other to far basic region between pH range of 7.8 and 10.0. IC was focused to the same basic region as a fraction of IgG migrated. Anti-DNA antibodies of IgG class, especially those focused to alkaline pH region (cationic antibodies) bound to phenylalanine (PH) column with high affinity. From these results, it was inferred that anti-DNA antibodies of IgG classes, especially those having high basic charge (cationic antibodies) showed a tendency to form IC and that the cationic antibodies may participate in the pathogenesis of tissue injury, especially of glomerulonephritis, in SLE.
 ...
PMID:[Analysis of anti-DNA antibody in sera from patients with systemic lupus erythematosus by isoelectric focusing with respect to autoantibody isotype and immune complex]. 155 62

Autoimmune aPL are associated with a well-defined clinical syndrome of vascular thromboses, recurrent fetal loss, thrombocytopenia, livedo reticularis, and valvular and neurologic abnormalities. A clinical diagnosis of SLE need not be present, and aPL syndrome in the absence of other well-defined autoimmune disease is termed PAPS. A positive test for aPL is defined by enzyme-linked immunoassay (aCL) or by functional coagulation assay (LAC). Anticardiolipin antibody and LAC are similar but probably not identical antibodies. The false-positive test for syphilis is less closely associated with clinical complications than are aCL and LAC. The mechanism of action of aPL is not yet known, although many theories have been advanced. Recent identification of beta 2-glycoprotein I, a serum glycoprotein, as an aPL cofactor suggests that inhibition of this protein's anticoagulant activity may be important. Autoimmune aPL differ from infection-induced aPL in important antibody characteristics, including IgG subclass, light chain preference, antibody avidity, and cofactor requirement. Both recognize negatively charged phospholipids, but various physical characteristics of the phospholipids alter the recognition patterns. Treatment of the aPL syndrome is not well defined. Anticoagulation with heparin, coumadin, or aspirin are currently widely used. Although corticosteroid, immunosuppressive therapy, and plasmapheresis may be used for severe, fulminant thrombosis, the efficacy of this treatment has yet to be proved.
 ...
PMID:Antiphospholipid antibody syndrome. 156 40

Antibodies against ENA (Extractable Nuclear Antigens), SSA/Ro and SSB/La were investigated in parallel in the serum and the immune complex precipitates of 41 patients with autoimmune disease (10 systemic lupus erythematosus, 23 discoid lupus erythematosus, 3 subacute cutaneous lupus erythematosus, and 5 progressive systemic sclerosis). It was demonstrated that in some cases the autoantibody spectrum of the serum did not coincide with that of the immune complex precipitate. In the majority of patients the protein content of isolated immune complexes was increased and the increase was attributed to IgG solely. In some patients antibodies appeared not only in the serum but also in immune complex, even in 4 patients (2 systemic lupus erythematosus, 1 subacute cutaneous lupus erythematosus, and 1 progressive systemic sclerosis) antibodies were detected only in the immune complex precipitate.
 ...
PMID:[Detection of circulating antibodies in the blood and immune complex precipitates of patients with autoimmune diseases (preliminary report)]. 157 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>