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

The methods currently used for the detection of ANA have been analyzed, with emphasis on their practical application to the diagnosis of the CTD. The use of the indirect IF-ANA test was recommended as a screening procedure to detect ANA. The need to standardize the technique using a single substrate and fluorescent conjugates with uniform F/P ratios was stressed. Most importantly, the value of titrating ANA for the diagnosis of the CTD was discussed. ANA titers higher than 1/500 are usually very significant clinically, often found in spontaneous or drug-induced SLE and few other CTD. The immunologic aspects of ANA and their potential value as aids in the diagnosis and management of the CTD were discussed. Anti-nDNA antibodies have been found to have a high degree of specificity for SLE and high titers of these antibodies correlate well with low levels of serum complement and severity of kidney involvement. The spectrum of ANA in the sera from patients with SLE has been expanded with the finding of anti-Sm antibodies which, when detected by gel precipitation with prototype serum, have been found so far only in SLE. Some of these antibodies have been found to have prognostic significance. Patients with MCTD and a group of patients with SLE have high titers of serum ANA with specificity for an RNase-sensitive component of ENA. The group of SLE patients defined by the presence of these antibodies (anti-Mo) have a better prognosis and in general develop only mild nephritis or have no kidney involvement at all. High titers of pure antinucleolar antibodies probably are found almost exclusively in the sera of patients with scleroderma. Some ANA have organ specificity, and GS-ANA have been found in all patients with Felty's syndrome and in a large proportion of patients with RA. One of the great advances in the field has been the recognition that ANA can be induced in the human and in experimental animals by the use of a number of therapeutic agents. Some of these agents can also induce a clinical picture resembling spontaneous SLE, though kidney involvement does not occur or is extremely mild. It is interesting that the whole spectrum of ANA can be found in drug-induced LE except anti-nDNA antibodies which have been associated to the pathogenesis of immune complex nephritis in spontaneous SLE. There is no doubt that research on ANA has contributed a great deal to the understanding of the CTD and will continue to be a valuable tool for the clinician and the investigator.
Semin Arthritis Rheum 1976 Nov
PMID:Antinuclear antibodies (ANA): immunologic and clinical significance. 6 98

Clinical and laboratory findings were correlated from 46 patients with IgG localization in epidermal nuclei in a speckled (particulate) pattern on direct immunofluorescence of normal skin. Cutaneous manifestations included lupus erythematosus (LE), swollen hands or sclerodactyly, alopecia, vasculitis, and dyspigmentation. Systemic manifestations included arthritis or arthralgia, Raynaud's phenomenon, serositis, vascular headaches, mild renal disease, myositis, and sicca syndrome. High titer (mean = 1:142, 800) serum antibody to extractable nuclear antigen (ENA) was found in 81%. Eighty-six percent had antibody to an RNase-sensitive antigenic component of ENA (ribonucleoprotein or RNP); 14% had antibody to an RNase-resistant ENA termed Sm. Deposition of IgG in a speckled pattern in epidermal nuclei is an immunopathologic marker for a subset of connective tissue disease characterized by antibody to ENA. Those with Sm specificity had systemic LE (SLE); Those with RNP specificity had Raynaud's phenomenon usually associated with overlapping features of SLE, scleroderma, and/or dermatomyositis.
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PMID:Speckled (particulate) epidermal nuclear IgG deposition in normal skin. Correlation of clinical features and laboratory findings in 46 patients with a subset of connective tissue disease characterized by antibody to extractable nuclear antigen. 34 15

Two antigens, temporarily referred to as MU and TM antigens after the original serum, that are closely related to the nucleolus have been identified in the nuclear soluble extract. Both antigens reacted with the sera of a small number of patients with various connective tissue diseases, and both were different from antigens described previously in these disorders. MU antigen was sensitive to the digestion with RNase and trypsin, and was shown to be equivalent to the nuclear ribosomal components in the nuclear extract. TM antigen was resistant to the digestion with RNase and trypsin, and was localized in the nucleolus and extranucleolar portion of nuclei, but the precise nature of TM has not been established.
Arthritis Rheum
PMID:Identification and characterization of two new soluble nuclear antigens reactive with sera of patients with connective tissue diseases. 35 92

Using immunoblot analysis with soluble nuclear extracts from HeLa cells, we identified autoantibodies to an antigen with a molecular weight of approximately 33,000 in 36% of 95 sera from rheumatoid arthritis patients, but in only 1 of 170 controls. The antigen, termed RA33, was resistant to DNase and RNase digestion but sensitive to proteinase K treatment. There was no discernible relation to other autoantibodies. Thus, this newly described autoantibody appears to be highly specific for rheumatoid arthritis.
Arthritis Rheum 1989 Dec
PMID:Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis. 259 7

We characterized serum from a patient with polymyositis, and found that it produced a peripheral (rim) fluorescent antinuclear antibody pattern on rat liver substrate. Indirect immunofluorescence analysis revealed a punctate pattern at the nuclear surface of PtK2, BHK-21, and HEp-2 cells. This pattern was still present after sequential extraction in situ with non-ionic detergent, DNase, RNase, and high ionic strength buffer (2M NaCl). Immunogold electron microscopic localization was specific for nuclear pore complexes. By immunoblot analysis, the antigens were polypeptides of 200 kd and 130 kd that were enriched in the nuclear fraction.
Arthritis Rheum 1988 Oct
PMID:A novel autoantibody causing a peripheral fluorescent antinuclear antibody pattern is specific for nuclear pore complexes. 305 60

A new antigen (Su) from calf thymus nuclear extract that reacts with sera from patients with systemic lupus erythematosus (SLE) is described. Antibodies to Su, demonstrated by immunodiffusion, were most frequently found in patients with a diagnosis of probable or definite SLE. Thirty-seven percent of patients with Su antibodies and a diagnosis of SLE were positive for antinuclear antibodies by indirect immunofluorescence, but lacked specific antibodies previously associated with SLE. Patients with Su antibodies exhibited a higher frequency of Raynaud's phenomenon, but exhibited a lower frequency of malar rash, alopecia, and arthritis when compared with SLE patients in previously published reports. The Su antigen is weakly acidic, heat-stable at 37 degrees C, heat-sensitive at 56 degrees C, resistant to DNase and RNase, but sensitive to trypsin. Its molecular weight approximated 154,000 daltons by Sepharose chromatography. The Su antibody may be associated with a subset of SLE patients with distinct clinical features, and may serve as a serologic marker for patients who are positive for fluorescent antinuclear antibodies but have no other detectable SLE-associated antibodies.
Arthritis Rheum 1984 Nov
PMID:Characterization of a new antigen-antibody system (Su) in patients with systemic lupus erythematosus. 649 21

Antibodies to extractable nuclear antigens (ENA) were analysed in the sera of fifty-two patients with severe rheumatoid arthritis (RA) who were divided into two categories: twenty-five with arthritis only and twenty-seven with extra-articular disease. Using haemagglutination, counterimmunoelectropheresis (CIE) and double diffusion, antibodies to ENA were detected in three (12%) of the patients with arthritis only. In the group with extra-articular disease, antibodies were found in sixteen (59%) of the patients. In ten patients the antibodies reacted with an RNase and DNAse resistant, but trypsin sensitive protein component of ENA. These patients all had extraarticular disease with digital vasculitis being a particularly common feature. Their sera also contained circulating immune complexes detected by elevated cryoprecipitate protein levels associated with relatively low complement levels. It is suggested that antibodies to soluble proteins of nuclear origin may be markers of circulating immune complexes in extra-articular RA.
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PMID:Antibodies to extractable nuclear antigens in rheumatoid arthritis: relationship to vasculitis and circulating immune complexes. 677 Oct 70

The ovine lentiviruses cause encephalitis, pneumonia, and arthritis in sheep worldwide. Visna virus is a prototype of this family and the pathogenesis and molecular biology of the virus has been well characterized. The envelope proteins of visna virus are responsible for binding of virus to host cells and for causing cell fusion. The surface glycoprotein also elicits cellular and humoral immune responses to the virus, the former being thought to be responsible for eliminating infected cells as well as causing inflammatory lesions. In this study, transgenic sheep were constructed that expressed the envelope genes of visna virus under the control of the visna LTR to investigate the role of the env gene in the pathogenesis of lentiviral disease in its natural host. Three transgenic lambs were identified that contain the env transgene and express the envelope glycoproteins. These transgenic animals have remained healthy and expression of the viral gene has had no obvious deleterious effect. Expression of the visna envelope protein was demonstrated by cell fusion mediated by the envelope gene as well as by immunoprecipitation of the envelope proteins with monoclonal antibodies and immunofluorescence analyses of Env protein in cells. The target cell for visna virus replication in infected animals is the monocyte/macrophage. In natural infection, the level of viral gene expression in these cells increases with cell maturation. In the transgenic sheep, monocytes did not express the envelope glycoproteins until they differentiated into macrophages in vitro. Expression of the env mRNA in macrophages was quantitated by an RNase protection assay. In addition to expression in macrophages, the transgene was expressed by fibroblasts isolated from skin of the transgenic sheep. Expression of both the Env and Rev proteins was detected by immunoprecipitation and immunofluorescence. Two of the three lambs responded immunologically to the expression of the transgene by producing binding antibodies to the envelope glycoproteins. Thus, these transgenic sheep provide a model to study whether a lentivirus glycoprotein will prevent infection or modulate disease in its natural host after virus challenge.
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PMID:Development of transgenic sheep that express the visna virus envelope gene. 817 28

Psoriasis is a chronic inflammatory skin disease that is often complicated by an inflammatory arthritis. Considerable evidence implicates cellular immune responses in psoriatic skin lesions, but the pathogenesis of the associated arthritis has not been elucidated. We analyzed T cell antigen receptor beta chain variable (TCRbetaV) gene repertoires among peripheral blood lymphocytes, skin and synovium of nine patients with psoriatic arthritis. RNase protection assays were used to quantitate the expression levels of 25 TCRbetaV genes, and CDR3 region sequencing was used to further characterize selected expansions. All patients exhibited significant TCRbetaV biases in the peripheral blood and moreover, all had expansions common to both skin and synovium. CDR3 sequencing demonstrated these expansions frequently consisted of oligo- or monoclonal populations. Although no ubiquitous CDR3 nucleotide sequences were identified, two patients shared identical sequences and several highly homologous amino acid motifs were present in skin and synovium among and between individual patients. Findings of common TCRbetaV expansions in diverse inflammatory sites, among multiple afflicted individuals, suggest that these T cell proliferations are driven by engagements with a limited set of conventional antigens. These findings demonstrate an important role for cognate T cell responses in the pathogenesis of psoriatic arthritis, and further suggest the inciting antigen(s) is identical or homologous between afflicted skin and synovium.
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PMID:Clonal characteristics of T cell infiltrates in skin and synovium of patients with psoriatic arthritis. 1040 97

Folates and folate antimetabolites are metabolically trapped in mammalian cells as polyglutamates, a process catalyzed by folylpoly-gamma-glutamate synthetase (FPGS). Using 5'-rapid amplification of cDNA ends, RNase protection assays, transfection of cDNAs into FPGS-deficient cells, and kinetic analysis of recombinant enzymes expressed in insect cells, it was determined that the species of active FPGS in mouse liver and kidney was different from that in mouse tumor cells, bone marrow, and intestine. The NH2-terminal peptide of hepatic enzyme contained 18 amino acids not found in enzyme from dividing tissues, and the specificity of the two isoforms for antifolates also differed, suggesting different architecture of the active sites. In most tissues, the expression of one isozyme or the other was an all-or-nothing event. The exclusive use of one of two alternative sets of initial coding exons in different tissues underlies this phenomenon, suggesting the design of antifolates specific for activation by individual FPGS isoforms and hence tissue-selective targeting of antifolate therapy for cancer, arthritis, or psoriasis.
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PMID:Tissue-specific expression of functional isoforms of mouse folypoly-gamma-glutamae synthetase: a basis for targeting folate antimetabolites. 1062 93


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