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)

Abnormalities of Hageman factor dependent pathways have been described in a wide variety of human disease states. Congenital deficiencies of factor XII (Hageman trait) prekallikrein (Fletcher trait) and high molecular weight kininogen (Williams, Fitzgerald and Flaujeac traits) although resulting in profound in vitro changes, do not cause in vivo difficulties. In contrast, deficiency of C1 esterase inhibitor (hereditary angioedema) results in significant morbidity and mortality. Acquired diseases may exhibit decreased synthesis of these three proteins in cirrhosis and dengue fever. In vivo activation of factor XII initiated pathways occur in septic shock, disseminated or localized intravascular coagulation, typhoid fever, polycythemia vera, hyperbetalipoproteinemia, coronary artery disease, nephrotic syndrome, transfusion reactions, hemodialysis and extracorporeal bypass. Activation of both the intrinsic system and tissue mediators contribute to the vasomotor phenomena in carcinoid syndrome and postgastrectomy dumping. Roles for factor XII, prekallikrein and kininogen have been suggested in gouty arthritis, allergic disorders and cystic fibrosis but the evidence is not yet convincing in these disorders.
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PMID:Participation of Hageman factor dependent pathways in human disease states. 34 10

Although both the complement and contact system are thought to contribute to the inflammatory reaction in arthritic joints, only activation of complement has so far been well established, whereas contact activation and its contribution to arthritis has not been systematically explored. Complement and contact activation were assessed in 71 patients with inflammatory arthropathies and 11 with osteoarthritis using sensitive assays for C3a, and C1-inhibitor (C1INH)-kallikrein and C1INH-factor XIIa complexes respectively. Increased plasma concentrations of kallikrein-and factor XIIa-C1INH complexes were found in two and seven of the 71 patients with inflammatory arthropathies, respectively, and in none of the patients with osteoarthritis. Increased synovial fluid concentrations of kallikrein and factor XIIa complexes occurred in 13 and 15 patients with inflammatory joint diseases respectively, and in two patients with osteoarthritis. Contact system parameters did not correlate with clinical symptoms, local activity, or neutrophil activation. In contrast, synovial fluid concentrations of C3a and C1INH-C1 complexes were increased in all patients and in 20 patients with inflammatory arthropathies respectively, and were higher in patients with a higher local activity score. Synovial fluid C3a correlated with parameters of neutrophil activation such as lactoferrin. Increased plasma concentrations of C3a and C1INH-C1 complexes occurred in 13 and 11 patients with inflammatory joint diseases, and in one and two patients with osteoarthritis respectively. Plasma concentrations of C3a correlated with the number of painful joints. Thus contact activation occurs only sporadically in patients with arthritis and contributes little if anything to the local inflammatory reaction and neutrophil activation. These latter events are significantly related to the extent of complement activation.
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PMID:Relative contribution of contact and complement activation to inflammatory reactions in arthritic joints. 144 25

Terminal complement complex (TCC) and C1r-C1s-C1 inhibitor complex (C1/C1 INH) concentrations were measured in plasma and synovial fluid from patients with arthritis and related to other measures of disease activity. Both TCC and C1/C1 INH concentrations were significantly increased in patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (plasma and synovial fluid, P less than 0.05) and normal subjects (plasma only, P less than 0.001). In the patients with RA, there was no correlation between plasma or synovial fluid TCC concentrations and IgM rheumatoid factor, immune complex or C1/C1 INH levels. However, in 10 patients with seronegative RA, C1/C1 INH and immune complex levels correlated significantly in synovial fluid (r = 0.69, P less than 0.05) although not in plasma (r = 0.52). Plasma and synovial fluid TCC and C1/C1 INH concentrations did not differ in rheumatoid patients with severe compared with mild joint disease (categorized by the Ritchie score). These results confirm a role for complement activation in RA but suggest that several mechanisms are involved in its pathogenesis.
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PMID:Terminal complement complexes and C1/C1 inhibitor complexes in rheumatoid arthritis and other arthritic conditions. 202 52

During activation, the first component of complement C1q (C1r-C1s)2 is dissociated in conjunction with the formation of complexes containing C1 esterase inhibitor (C1-INH). Trimer complexes, with zymogen C1s associated with a firm C1-INH-C1r complex (C1-INH-C1r-C1s) can be distinguished from tetramer complexes C1-INH-C1r-C1s-C1-INH) in which C1-INH is firmly bound to both proteases. In the present study a two-stage electroimmunoassay was developed for the specific measurement of C1-INH-C1r-C1s. In the first step, C1-INH and its complexes were immunoprecipitated with anti-C1-INH during electrophoresis in the presence of Ca2+. In the second step, C1s contained in C1-INH-C1r-C1s was dissociated in the presence of EDTA and was measured by immunoprecipitation with anti-C1s. C1-INH-C1r-C1s were consistently found in normal sera. Normal sera did not contain C1-INH-C1r-C1s-C1-INH as assessed with a previously described ELISA procedure. Sera and synovial fluids from two groups of patients with inflammatory arthritis were investigated. In rheumatoid arthritis patients (n = 15) C1-INH-C1r-C1s complexes were usually found at high concentration both in serum and synovial fluid. C1-INH-C1r-C1s-C1-INH complexes were also present with values that were higher in synovial fluid than in serum, in accord with previous findings of classical pathway activation in the inflamed joints of the patients. Patients with spondylarthritic syndromes (n = 7) had serum and synovial fluid C1-INH-C1r-C1s concentrations that were comparable to those of the rheumatoid arthritis patients. If at all present, C1-INH-C1r-C1s-C1-INH were detected in trace amounts. Thus, C1 activation in patients with spondylarthritic syndromes appeared to be efficiently controlled at the C1r level. Distinguishing between C1-INH-C1r-C1s and C1-INH-C1r-C1s-C1-INH may prove of value in further studies of the activation and control of C1 in disease.
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PMID:Trimer and tetramer complexes containing C1 esterase inhibitor, C1r and C1s, in serum and synovial fluid of patients with rheumatic disease. 233 98

Fibroblast-like cells from synovial tissue obtained during arthroscopy in 4 young adults with recent knee trauma were biosynthetically labeled with 35S-methionine, and protein production was quantitated by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Synovial fibroblast-like cells synthesized C1r, C1s, C1 inhibitor, C2, C3, factor B, and factor H, all with the same sizes and subunit structures as the proteins synthesized in skin fibroblasts. The capacity to synthesize these proteins was not lost with passages or freeze-thawing. Gamma-interferon stimulation increased synthesis of all 7 proteins. Lipopolysaccharide increased synthesis of only C3 and factor B. Unlike in whole rheumatoid tissue, C4 and C5 were not detected. Synovial lining cells may be an important source of local complement for participation in local defense or development of pathologic states.
Arthritis Rheum 1988 Nov
PMID:Synovial fibroblast-like cells synthesize seven proteins of the complement system. 314 87

Ninety-three serum and plasma samples from 45 patients with systemic lupus erythematosus were analyzed for the complex formed by C1s and its inhibitor, as well as for C3, C4, C4a desarginine, and staphylococcal protein A-bound immune complexes. There were statistically significant correlations between C1s-C1 inhibitor complex and CH50, between C1s-C1 inhibitor complex and C4, and between C1s-C1 inhibitor complex and C4a desarginine. Serial studies were performed on 24 patients over a period of 6 months. Seven of 21 patients with hypocomplementemia had persistently normal levels of C1s-C1 inhibitor complex, 7 had transiently abnormal levels of C1s-C1 inhibitor complex, and 7 had sustained abnormal levels of C1s-C1 inhibitor complex. Two of 3 pregnant patients with normal levels of complement had abnormal levels of C1s-C1 inhibitor complex. Staphylococcal protein A-bound immune complexes demonstrated no correlation with any of the complement assays. Complement activation, as measured by C1s-C1 inhibitor complex, is often a transient phenomenon in systemic lupus erythematosus patients with persistent hypocomplementemia.
Arthritis Rheum 1986 Dec
PMID:Hypocomplementemia with low C1s-C1 inhibitor complex in systemic lupus erythematosus. 349 8

A 58-year-old man with end-stage renal disease treated with long-term ambulatory peritoneal dialysis gave a history of hereditary angioedema. Results of testing of his serum for antinuclear antibody were strongly positive, and a titer of 1:2,560 for antiribosomal antibody was documented. Three of his six children reported multiple medical problems, including episodic swelling, discoid lupus, and arthritis. An indepth study of this kindred showed a number of associated immunologic disturbances. Three children had decreased C1 esterase inhibitor and decreased C4 levels. T cell enumeration revealed low proportions of suppressor cells in these three children as well as in another unaffected child. Serum IgM level was low in the propositus, and IgG level was also decreased in one of the affected children. HLA typing failed to show a clear association of class I or class II antigens with hereditary angioedema. Family members tested did not demonstrate anti-SS-A, anti-SS-B, antinuclear antibody, anti-double-stranded DNA, anti-Sm, or anti-ribonuclear protein antibodies.
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PMID:A family with hereditary angioedema and multiple immunologic disorders. 357 41

To explore the causes of complications in pregnant women with systemic lupus erythematosus (SLE), we prospectively evaluated 34 pregnancies in 28 SLE patients, and 2 additional pregnancies in patients with lupus anticoagulant and positive antinuclear antibody, but no other manifestations of SLE. Nineteen pregnancies (55%) were complicated by marked proteinuria, thrombocytopenia, and/or lupus anticoagulant. Hypocomplementemia occurred in 18 pregnancies (52%). Neither thrombocytopenia-anticoagulant nor proteinuria was accompanied by an increase in antibody to double-stranded DNA or by clinical signs of active SLE. Antibody to Ro antigen did not predict fetal death. Both thrombocytopenia and proteinuria appeared abruptly during pregnancy and disappeared quickly after delivery. Fetal death was the result in 7 of 9 (77%) pregnancies in patients with anticoagulant, 6 of 10 (60%) in patients with thrombocytopenia, 6 of 18 (33%) in patients with hypocomplementemia, and 3 of 11 (27%) in patients with proteinuria. Twenty of 29 (68%) children were identified as male. The pathogenesis of hypocomplementemia was evaluated by a new assay, C1s-C1 inhibitor complex, which is thought to measure rate of complement activation by the classical pathway. Most pregnant patients with low CH50 levels and proteinuria had normal levels of C1s-C1 inhibitor complex, whereas nonpregnant patients with equivalent proteinuria and hypocomplementemia had high levels, as did pregnant patients with hypocomplementemia who did not have SLE. Pregnant and nonpregnant hypocomplementemic patients with proteinuria had similar levels of C3 and C4. In pregnant patients with SLE, C1s-C1 inhibitor complex was independent of CH50; in nonpregnant patients a linear relationship between C1s-C1 inhibitor complex and CH50 was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Arthritis Rheum 1985 Jan
PMID:Lupus pregnancy. II. Unusual pattern of hypocomplementemia and thrombocytopenia in the pregnant patient. 391 71

Since 1973, we have identified and collected follow-up data on 16 patients with hypocomplementemic urticarial vasculitis. Preliminary diagnostic criteria are the presence of typical urticarial skin lesions and low levels of serum complement (all components), plus two of the following: dermal venulitis, arthritis, glomerulo-nephritis, episcleritis or uveitis, recurrent abdominal pain, and C1q precipitin in plasma. Exclusions are systemic lupus erythematosus, mixed cryoglobulinemia, elevated antinuclear antibody titer, hereditary deficiency of a complement component or of C1 esterase inhibitor, and presence of anti-native DNA or hepatitis B antigen. The renal involvement is relatively benign, and generally the patients do well and respond to specific treatment when this is indicated. Eight of 10 smokers studied had evidence of chronic obstructive pulmonary disease, 1 of whom died of this complication. In three patients, severe chronic obstructive pulmonary disease developed at a young age after relatively low pack-year cigarette smoking histories. Lung disease probably results from the interaction of two major risk factors-smoking and an immunologically mediated process that has not been identified.
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PMID:Hypocomplementemic urticarial vasculitis: association with chronic obstructive pulmonary disease. 704 Aug 25

We describe a patient with hereditary angioedema (HAE), showing recurrent edema around the peripheral joints. Her symptoms began at the age of 18 with hand swelling distal to the wrist joints. Until she was referred to our hospital 3 years after her initial symptoms, she was still undiagnosed, although she was suspected of having rheumatoid arthritis. Laboratory examination showed reduced levels of CH50 and C4 with normal C3 levels. The C1 inhibitor (C1-INH) was decreased to 5 mg/ml, with remarkably reduced activity. Although these findings were compatible with a diagnosis of HAE, there were no episodes of skin edema in her family. To establish the diagnosis, we carried out DNA analysis of the C1-INH gene, which revealed a newly identified de novo mutation of G to A at nucleotide 16869 in exon 8. As described in this patient, localized edema around the peripheral joints may be the only manifestation of HAE. HAE should therefore be taken into consideration for the differential diagnosis of joint swelling.
Arthritis Rheum 2001 Apr
PMID:Hereditary angioedema with a de novo mutation of exon 8 in the C1 inhibitor gene showing recurrent edema of the hands around the peripheral joints: importance for the differential diagnosis of joint swelling. 1131 37


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