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

Serum concentrations of C4, C3, factor B (B), properdin (P), C3b inactivator (C3bINA) and beta 1H globulin have been measured by radial immunodiffusion in sixty-two samples from thirteen patients with systemic lupus erythematosus (SLE). Significant reductions in the mean serum concentrations of C4 (classical pathway) B and P (alternative pathway) and C3 were found. In addition, the mean level of the control protein beta 1H, but not C3bINA, was reduced. Sera from thirteen patients taking during disease exacerbation (low C3) showed significantly lower levels of both C3bINA and beta 1H than sera taken from the same thirteen patients during disease remission (high C3). Serum concentrations of C3bINA correlated with B (P less than 0.005) but not C4, C3 or P, whereas levels of beta 1H correlated with C4 (P less than 0.01), B (P less than 0.005) and properdin (P less than 0.01). Serial measurements of the serum concentrations of C3bINA and beta 1H showed that levels of these protein fell during exacerbation, and such falls were more closely associated with diseases in the serum levels of the alternative pathways proteins than C4. It is concluded from these observations that serum concentrations of the control proteins C3bINA and beta 1H, especially the latter, control the extent of turnover of the alternative pathway in SLE. Metabolic studies are required to determine the causes of the decreased serum concentrations of these control proteins.
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PMID:Relative importance of C3b inactivator and beta 1H globulin in the modulation of the properdin amplification loop in systemic lupus erythematosus. 11 47

To assess the relative roles of the classic and alternative pathways of complement activation in chronic discoid lupus erythematosus (CDLE), serum levels of properdin, C3, and C4, and deposition of these proteins in the dermal-epidermal junction (DEJ) of 20 CDLE patients were compared to the findings in patients with clinically active and inactive SLE. Properdin was demonstrated in the DEJ of 10 of 14 (71%) histologically typical skin lesions from patients with CDLE, usually in association with deposits of immunoglobulin, C3, and C4. Properdin levels in CDLE patients were significantly increased (137 +/- 34%) (P less than 0.05) when compared to normal controls (101 +/- 18%) or to patients with clinically active SLE (89 +/- 32%). C3, C4, DNA-binding, and antinuclear antibody tests in CDLE were indistinguishable from those in normals, but significantly different from patients with active SLE (P less than 0.05). The complement profiles of patients with clinically inactive SLE resembled those of CDLE patients more closely than those of active SLE patients.
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PMID:Pathways of complement activation in chronic discoid lupus: serologic and immunofluorescence studies. 32 68

The complement system may be activated by two pathways, the classical and the alternate. To evaluate their respective participation in different forms of glomerulonephritis, the plasma values of C3, C4, C3PA, C1q and properdin were determined in 70 patients. In systemic lupus erythematosus (LED), acute poststreptococcal glomerulonephritis (AGN) and septicemia the classical pathway appears to be mainly involved, whereas the amplification loop and the alternate pathway seem to be of secondary importance. By contrast, in membranoproliferative glomerulonephritis (MPGN) the alternate pathway plays a major role. However, the present data suggest that activation of the classical pathway may often be involved as well. In minimal change glomerulonephritis no signs indicating involvement of the complement system were apparent. Follow-up observation demonstrated a correlation between decreases in plasma complement concentrations and the clinical severity of the primary disease in LED, AGN and septicemia, but not in MPGN.
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PMID:[Activation of the complement system in different forms of glomerulonephritis]. 33 69

The clinical history, deposition of IgG, IgM, IgA, C3, C4 and properdin at the dermal-epidermal junction (DEJ) of clinically normal skin, serum ANA, DNA-binding, C3, C4, Factor B, and properdin were compared in 27 systemic lupus erythematosus (SLE) probands, 21 first-degree household contact relatives (FDHCR), 19 first-degree nonhousehold contact relatives (FDNHCR), 15 spouses, 26 controls, and 16 chronic discoid lungs lupus erythematosus patients. Female consanguineous relatives of SLE patients had a higher incidence of rheumatic symptoms than male relatives (P less than 0.01). Female FDHCR and male spouses had a higher incidence of protein deposition at the DEJ than sex-matched controls (P = 0.026 and 0.0028). The incidence of protein deposition at the DEJ in FDNHCR did not differ from sex-matched controls. ANA titers of the consanguineous relatives were significantly higher than those of the spouses or sex-matched controls irrespective of household contact with their proband. The observation of protein deposition at the DEJ in normal appearing skin of FDHCR and spouses suggests the importance of environmental factors, whereas the elevations of ANA titers in consanguineous relatives suggests the importance of genetic factors in the pathogenesis of SLE.
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PMID:Family study of systemic lupus erythematosus: analysis of the clinical history, skin immunofluorescence, and serologic parameters. 33 83

Although an unusually high incidence of immunological diseases has been described in patients with hereditary C2 deficiency, the severity of these illnesses has been relatively mild, suggesting that blocking complement activation beyond C4 may protect against significant complement-mediated inflammation. This report describes studies in a C2-deficient patient with severe systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis. An immunopathological study of the kidney revealed the deposition of properdin, properdin factor B, C3 and C5 in a pattern similar to immunoglobulin G deposits. Serum properdin and properdin factor B levels were low at various times during the patient's course. In vitro complement fixation studies showed C3 fixation by glomerular deposits could occur via the alternative pathway. Studies of the immune deposits in the patients' skin revealed similar results. These studies suggest that inflammation may be effectively mediated via the alternative complement pathway in the C2 deficiency-lupus syndrome.
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PMID:Hereditary C2 deficiency and systemic lupus erythematosus associated with severe glomerulonephritis. 34 63

The clinical details of a five-year-old boy with systemic lupus erythematosus and an inherited deficiency of the fourth component of complement (C4) have been reported elsewhere. In this study of his immune responses, immunization with bacteriophage phi X 174 demonstrated diminished antibody formation, abnormal immunologic memory and failure to switch from IgM to IgG during secondary response. We also noted persistent lymphopenia and reductions in peripheral-blood T lymphocytes, lymphocyte responses to mitogens and allogeneic cells and granulocyte chemotaxis. Kinetic studies revealed that delayed activation of the alternative pathway was corrected by purified C4 only if the classical pathway was not blocked. This finding is consistent with the concept that minute amounts of C3b provided through the classical pathway are necessary to prime the properdin system. Inability to activate the classical complement pathway, abnormal kinetics of alternative-pathway activation and depressed antibody responses to a T-cell-dependent antigen may predispose C4-deficient patients to viral infection or immune-complex formation.
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PMID:Immune response of a patient with deficiency of the fourth component of complement and systemic lupus erythematosus. 43 36

The electrophoretic mobility of properdin in agarose with and without EDTA examined in sera from normal subjects and from patients with mesangiocapillary glomerulonephritis, systemic lupus erythematosus, rapidly progressive glomerulonephritis, mesangial IgG-IgA disease, minimal change glomerulonephritis and partial lipodystrophy. In 'EDTA agarose", the properdin arc of normal serum was always cathodal (gamma), whereas in non-EDTA agarose it was always (beta), indicating that agarose activated properdin with its consequent conversion from a cathodal to an anodal form. Using this change in the mobility of properdin to investigate activation of the properdin system, it was found that the lower the C3 concentration of diseased sera, the less able were they to support properdin conversion by non-EDTA agarose. This relationship we interpret as a manifestation of the requirement of an intact C3b feedback pathway for properdin activation. This view was supported experimentally by (i) decreasing ability of non-EDTA agarose to shift properdin mobility in normal serum as it was progressively depleted of components of the alternative pathway by cobra venom factor, C3 nehritic factor or Mg2+, and (ii) the inability of non-EDTA agarose to shift properdin in sera depleted of C3 or factor B, and in serum deficient in C3. The report of other workers that activated properdin causes generation of C3b, coupled with our finding that properdin activation depends on the C3b feedback, indicates that a system exists in which activation of the C3b feedback cycle allows activation of properdin, allowing in turn further amplification of the C3b feedback. That the anodal form of properdin may be a property of activated properdin was shown by our observations that properdin eluted from zymosan was anodal and activated, and that the properdin in the supernatant normal serum incubated with inulin was anodal.
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PMID:Mechanisms of activation of the properdin system. Studies on properdin electrophoretic mobility in agarose activation of the alternative pathway. 81 32

C3b inactivator (C3bINA) has been measured in biologic fluids by radial immunodiffusion using a monospecific antiserum prepared in rabbits, and by a hemolytic assay which measures the reduction in the capacity of EAC43 cells bearing limited C3b sites to form C3B, the alternative pathway C3 convertase. The radial immunodiffusion and hemolytic assays show a good correlation (r = 0.86 P less than 0.001). Measurement of C3bINA concentrations in the sera of patients with systemic lupus erythematosus showed that during exacerbations of disease activity C3bINA concentrations tended to be lower, usually in association with reductions in C4, C3, factor B, and properdin, and sometimes with reductions of the alternative pathway proteins, factor B, and properdin alone. Supranormal values for C3bINA were found in the sera of 14 of 20 patients with seropositive rheumatoid arthritis and 3 of 9 seronegative patients, but none of 7 patients with degenerative joint disease. Synovial fluid concentrations of C3bINA, after correction for total synovial fluid protein and serum concentration of the enzyme, were significantly reduced in patients with rheumatoid arthritis compared to patients with degenerative joint disease (P less than 0.05). In both serum and synovial fluid from patients with rheumatoid arthritis, there was a good correlation between the concentrations of C3bINA and those of C3, factor B, and properdin, but not that of C4, suggesting that levels of C3bINA may serve to modulate recruitment of the properdin amplification loop in this disease.
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PMID:C3b inactivator in the rheumatic diseases. Measurement by radial immunodiffusion and by inhibition of formation of properdin pathway C3 convertase. 81 59

The prevalence of homozygous and heterozygous deficiency of the second component of complement (C2) was determined in patients with rheumatic disease including 137 with systemic lupus erythematosus (SLE), 274 with juvenile rheumatoid arthritis, and 134 with rheumatoid arthritis. 1 C2 homozygous deficient and 19 possible heterozygous deficient individuals were identified by using both immunochemical and functional assays to determine C2 levels. Of the 20, 8 had SLE (5.9%), 10 had juvenile rheumatoid arthritis (3.7%), and 2 had rheumatoid arthritis (1.4%), the homozygous deficient individual having SLE. The prevalence of C2 deficiency in the SLE and juvenile rheumatoid arthritis patients was significantly increased (P = 0.0009 and P = 0.02, respectively) when compared with controls, 6 (1.2%) of 509 blood donors having C2 levels consistent with heterozygous deficiency. 15 of the 20 C2 deficient patients were HLA typed and found to have antigens A10(Aw25), B18, or both. The patients with C2 deficiency and SLE had earlier age of onset of disease and less antinuclear antibody when compared with the C2 normal SLE patients. 11 families of the propositi were studied and found to have one or more C2 heterozygous deficient individuals. The family members had an equal distribution of rheumatic disease and antinuclear antibody in the C2 deficient and C2 normal groups. C2 deficient individuals were found to have significantly lower levels of properdin Factor B (242 mug/ml+/-54) when compared with the non-C2 deficient family members (282 mug/ml+/-73). These data support the concept that inherited deficiency of C2 is significantly associated with both SLE and juvenile rheumatoid arthritis.
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PMID:Inherited deficiency of the second component of complement. Rheumatic disease associations. 96 92

Rheumatoid arthritis (RA) was differentiated from systemic lupus erythematosus (SLE) by direct immunofluorescent techniques on skin specimens, using monospecific antisera for IgG, IgM, C3, C1q, properdin, and fibrin. Of 30 patients with RA studied, 20 had dermal vessel deposits of immunoglobulins and complement components in unaffected skin without the characteristic dermal-epidermal junctional fluorescence of SLE. Of 24 SLE patients studied, 24 had granular deposits of immunoglobulins and complement components in unaffected skin at the dermal-epidermal junction.
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PMID:Immunoglobulin and complement deposition in skin of rheumatoid arthritis and systemic lupus erythematosus patients. 97 Sep 89


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