UMLS:C0024141 - FACTA Search

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Query: UMLS:C0024141 (systemic lupus erythematosus)
44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with a hereditary deficiency of the second component of complement and discoid lupus erythematosus with features of systemic lupus erythematosus was studied. The propositus had a 9-year history of rash and arthralgia. Transient renal disease had completely resolved; there was a history of seizures. Examination of his serum disclosed antinuclear antibodies but no total haemolytic complement activity. C2 was absent. Serum concentrations of C1s, C3, C5 and C9 were elevated; other complement components were present in normal concentration, including C3 pro-activator. The patient's C3 pro-activator was electrophoretically converted by inulin and four of five lipopolysaccharides, but was poorly converted by aggregated human IgG. Two separate turnover studies with radiolabelled C3 showed fractional catabolic rates of 3-03 and 2-48% of the remaining plasma pool/hr (range of three normals: 1-62-2-18%/hr); and estimated C3 synthetic rates of 2-74 and 2-31 mg/kg/hr (range of three normals: 0-89-1-40 mg/kg/hr). Serum complement profiles of the patient's family demonstrated that the C2 deficiency was inherited as an autosomal codominant. One sibling, homozygous for C2 deficiency, and three other siblings, both parents and one daughter, all heterozygous for C2 deficiency, are in good health. Immunofluorescent studies of the patient's diseased skin exhibited substantial deposits of IgG, IgM, C1q, and C4 but not of later acting complement components, properdin, or C3 proactivator. These studies do not support the notion that inflammation in C3-deficient individuals with lupus erythematosus is mediated by the alternative complement pathway.
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PMID:C3 metabolism in a patient with deficiency of the second component of complement (C2) and discoid lupus erythematosus. 108 39

Skin lesions and clinically normal skin of thirteen patients with systemic lupus erythematosus (SLE) were examined, by the use of immunofluorescent techniques, to determine the presence of CIq, C3, C3 proactivator (C3PA), properdin, immunoglobulins (IgG, IgA, and IgM), and fibrin. IgM deposition was present in all thirteen skin lesions and in eleven normal areas tested, whereas IgG deposition occurred in eleven of the lesions but in only six normal areas. IgA was the least frequently encountered immunoglobulin. CIq deposition occurred in all thirteen skin lesions, and C3 deposition was present in twelve. Seven of nine and eight of eleven clinically normal areas demonstrated CIq and C3 deposition, respectively. Although less intense that CIq and C3 deposition, properdin deposition occurred in eight of the thirteen skin lesions tested but in only two of nine normal areas. C3PA deposition was of greater intensity than was properdin, but was seen in only five lesions and three clinically normal areas. Seven skin lesions and two normal areas also demonstrated fibrin deposition. Although alternate pathway activation is apparent, our findings suggest that the classical pathway (CI to C9) is the primary complement pathway involved in SLE skin.
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PMID:Dermal-epidermal deposition of complement components and properdin in systemic lupus erythematosus. 109 24

Properdin deposition has been recognized in glomeruli of patients with acute and chronic nephritis and lupus nephritis, and low serum properdin levels have been found in these disorders. These findings suggest that properdin may be involved in the production of glomerular damage and that low properdin levels may be due to hypercatabolism. The study was designed to examine the metabolism of properdin in normal subjects and to look for an abnormality in five patients with systemic lupus erythematosus with renal involvement and in six patients with membranoproliferative glomerulonephritis or dense deposit disease (MPGN). Highly purified human properdin was prepared by elution from zymosan, followed by DEAE-cellulose and carboxymethyl-Sephadex chromatography, and labeled with 125I by the iodine monochloride method. Parameters of metabolism were determined by monitoring plasma and urinary radioactivity at frequent intervals after the intravenous injection of 1-2 muCi of labeled material. The fractional catabolic rate (FCR) of properdin in normal subjects was found to have a very narrow range of 0.78-1.0,% of the plasma pool per hour (mean 0.95%). In systemic lupus erythematosus, the FCR was regularly elevated with a range of 1.21-2.30% (mean 1.70%). In MPGN, FCR was elevated in three patients (1.22, 1.94, and 2.08%) and within or below the normal range in three (0.78, 1.00, and 1.00%). Properdin levels were reduced in two patients who had the highest FCR's noted in the study. Properdin synthetic rates in normals varied from 4.1 to 14.3 mug/kg per h (mean 9.1) and was not found to be reduced in any patient. Properdin catabolism was found to be normal in a patient deficient in the C3b inactivator. These studies show that properdin is hypercatabolized in patients with renal disease and that decreased properdin levels when they occur in these patients can be entirely explained on the basis of this hypercatabolism.
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PMID:Metabolism of properdin in normal subjects and patients with renal disease. 115 85

The complement system may be activated by at least two different pathways: the clinical pathway involving C1, C4 and C2 and the alternative pathway involving properdin, C3, factor B and factor D. The classical pathway can be activated by antigen antibody complexes, while the alternative pathway can be activated by other substances such as natural polysaccharides. Both pathways lead to an activation of C3 and of the last complement components (C5 to C9). Congenital defects of the complement system have been described for several components. Some of these defects are relatively well tolerated, but others, such as C3 deficiency, lead to increased susceptibility to bacterial infections. Acquired complement defects are frequently observed in association with several diseases. Usually they are characterized by an increased level of complement components involved in the classical pathway and therefore reflect activation by antigen antibody complexes. Such changes may be systematic, as in lupus erythematodes, or localized to some biological fluids such as synovial fluid in rheumatoid arthritis. In some renal diseases the complement profile suggests activation of the complement system by the alternative pathway, and this may reflect a different pathogenesis.
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PMID:[The complement system]. 121 99

61 biopsies of normal skin from the deltoid area and lesional skin from various sites from 48 patients with systemic lupus erythematosus (SLE) were studied for the presence of properdin, C3, C4, and immunoglobulins (IgG, IgM, and IgA) in the dermal-epidermal junction (DEJ) using direct and indirect immunofluorescence. Properdin was present in 50% of normal and 40% of lesional skins. Properdin was present without C4 in only 2 of 38 nonlesional skin biopsies and in only 2 of 20 lesions. There was no significant difference in incidence of deposition of any of the six proteins studied between nonlesional and lesional skin. The frequency of deposition of each of the proteins correlated with clinical disease activity. The presence of proteins in the DEJ did not correlate with the presence of active renal disease at the time of biopsy nor with previously documented active nephritis. In addition, no other single clinical manifestation correlated with the presence of DEJ deposition of any protein studied. IgA was not demonstrated in the DEJ of nonlesional skin of 16 patients in remission and was present in 7 of 23 patients with active disease (P less than 0.05). Deposition of properdin in lesional skin correlated with the presence of extracutaneous disease activity (P less than 0.05). Analysis of serologic studies on serum obtained at the time of biopsy revealed a statistically significant correlation between C4 and C3 (r = 0.67). This correlation was stronger than that between properdin and C4 (r = 0.37). Titer of antinuclear antibody and percent of DNA binding correlated better with C4 levels than with properdin levels. Serum properdin levels were significantly lower in patients with active disease than in those in remission (P less than 0.05). Serum properdin levels were significantly lower in patients with properdin deposits in lesional skin than in those without properdin deposits. The data suggest that both alternative and classical pathways are activated in patients with clinically active SLE.
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PMID:Clinical significance of serum properdin levels and properdin deposition in the dermal-epidermal junction in systemic lupus erythematosus. 124

The study of complement deficiency states and their influence on immune function has generated new insights and still provides a challenge to continued investigation. The association of classical pathway deficiencies (C1, C4, C2 or C3) with immunological diseases such as SLE and glomerulonephritis has contributed to current knowledge concerning complement-dependent immune complex handling and elimination. Susceptibility to systemic infection with encapsulated bacteria is encountered in most forms of inherited complement deficiency. Recurrent neisserial infection is the only clinical manifestation clearly associated with defects of the membranolytic sequence C5-C9, while deficiency of properdin, a component of the alternative activation pathway, appears to predispose to nonrecurrent meningococcal disease. Inherited complement deficiency is rare, but the perspective is widened by the more common occurence of acquired defects in immunological diseases, and the apparent requirement for efficient complement recruitment in host defense. Another aspect is the possibility that complement deficiency might alleviate or prevent inflammatory symptoms. Notably, complement deficiency has not been reported in classical rheumatoid arthritis. Considerations of this kind would be refuted or modified by findings of complement deficiency in single patients.
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PMID:Inherited complement deficiency states: implications for immunity and immunological disease. 214 5

Complement profiles on 22 hypocomplementemic patients with membranoproliferative glomerulonephritis (MPGN) type I, on 11 with MPGN II, and on 16 with MPGN III, gave evidence that the nephritic factor of the amplification loop (NFa) is responsible for the hypocomplementemia in MPGN II and the nephritic factor of the terminal pathway (NFt) for the hypocomplementemia in MPGN III. In contrast, in MPGN I, there was evidence for three complement-activating modalities, NFa, NFt, and immune complexes. As a result, four different patterns of complement activation were seen. NFa, found in MPGN II, produces a complement profile characterized mainly by C3 depression. In addition, four of seven (57%) severely hypocomplementemic MPGN II patients (C3 less than 30 mg/dL) had slightly depressed levels of factor B, and one of seven (14%) of properdin, but in all the C5 concentration was normal. In contrast, all eight severely hypocomplementemic patients with MPGN II had depressed C5 and properdin levels, and six of eight (75%) depressed levels of C6, C7, and/or C9. Of eight MPGN III patients with moderate hypocomplementemia, 50% had depressed C5 and properdin levels and the remainder, depressed C3 only. This spectrum of profiles is most likely produced by varying concentrations of NFt. In MPGN I, nine of 23 (39%) had a profile indicating only classical pathway activation; seven of 23 (39%), a pattern compatible with NFt alone; four of 23 (9%), evidence for both classical pathway activation and NFt; and three of 23 (13%), a pattern compatible with NFa. The unique multifactorial origin of the hypocomplementemia in MPGN I, often giving evidence of classical pathway activation, together with previously reported differences in glomerular morphology and clinical features at onset, makes it distinct from MPGN III. Depressed C8 levels were found to some extent in all hypocomplementemic states. The levels were uncommonly depressed in patients with NFa, most markedly depressed with NFt, and moderately reduced with classical pathway activation. The cause is not known. Diagnostically, profiles showing classical pathway activation and low levels of C6, C7, and/or C9 are specific for MPGN I. Those showing only classical activation are likewise diagnostic of MPGN I if systemic lupus erythematosus (SLE) and chronic bacteremia are ruled out.
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PMID:Patterns of complement activation in idiopathic membranoproliferative glomerulonephritis, types I, II, and III. 220 97

The activation of complement components in human serum has been studied using immunoglobulins adsorbed to microtiter plates. The sequential deposition of complement fragments was detected by a series of mono- and polyclonal antibodies in an indirect enzyme-linked immunosorbent assay (ELISA). Antibodies against C1q, C1s, C4b/d, C3b/d, factor B, C5b-9 membrane attack complex (MAC), the regulatory complement proteins C4 binding protein (C4bp) and properdin were reactive. Several lines of evidence suggest that complement activation was via the classical pathway: (1) complement activation was highly isotype-restricted with regard to the adsorbed Igs (human IgG1 and IgG3 as well as mouse IgM, IgG2a and IgG2b isotypes are strong activators in contrast to human IgG2, IgG4, IgA and mouse IgG1); (2) Ca2+ depletion, heat treatment (56 degrees C for 45 min), incubation with 0.5 M KSCN or heat-aggregated immunoglobulins (aggIgG) abrogated serum activity; (3) complement deficient sera (C1q def', C2 def', C6 def' human sera; C2 def', C4 def' guinea pig sera) showed impaired deposition of the complement components that follow the missing component in the cascade of activation. In a clinical study sera from patients with systemic lupus erythematosus (SLE) were investigated in order to measure the effect of hypocomplementemia due to complement consumption. The results obtained suggest that this new and simple assay is well suited for (1) the detection of various inherited complement deficiencies, (2) the semiquantitative evaluation of sera with decreased complement levels, (3) a more detailed study of complement components bound to a solid phase.
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PMID:Deposition of complement activation products on plastic-adsorbed immunoglobulins. A simple ELISA technique for the detection of defined complement deficiencies. 280 24

Three of four children in a family have homozygous (less than 1% of normal) deficiency of factor H of the complement system and both parents, who are first cousins, are heterozygous for the same defect. The father and two of the H-deficient siblings also have a partial C2 deficiency. One of the children with combined deficiencies is affected by systemic lupus erythematosus with nephritis. No increased susceptibility to infections has been observed in the family. H deficiency is inherited in an autosomal codominant manner and is independently transmitted from C2 deficiency and HLA haplotypes. In the homozygous state it is associated with very low serum concentrations of B and C3, barely demonstrable as activated molecules. C5 is greatly reduced (less than 5%). Also, properdin and C6-9 are decreased. The findings in this family demonstrate that the occurrence of systemic lupus erythematosus in one of the children affected by a combined deficiency of factor H and C2 raises the question whether this pathology is related to the complete factor H or to the heterozygous C2 deficiency. Complete H deficiency is not necessarily accompanied by overt illness.
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PMID:Combined homozygous factor H and heterozygous C2 deficiency in an Italian family. 296 9

We describe an ELISA for assessment of complement function based on the capacity of serum to support fixation of complement components to solid phase immune complexes (IC). Microplates were coated with aggregated bovine serum albumin (BSA) followed by rabbit anti-BSA IgG. The solid phase IC were reacted with human serum. The uptake of C3b, C4b and properdin was measured using biotinylated F(ab)2 antibodies to each of the proteins, avidin alkaline phosphatase, and paranitrophenyl phosphate. Serial samples obtained from 15 patients with systemic lupus erythematosus were investigated. Out of 72 sera, 24 showed a reduced capacity to support incorporation of C4b into solid phase IC. Thirty-one of the sera showed low C3b binding and 59 of the sera a reduced uptake of properdin. The incorporation into solid phase IC of C3b and C4b as well as of C3b and properdin were closely correlated at high disease activity. In general, patients with severe disease manifestations showed low values in the uptake assays. Judging from the results obtained by analysis of serial samples, the uptake of C3b, C4b and properdin, complement mediated solubilization of fluid phase IC and the concentrations of C1q binding IC were useful indicators of disease activity in the patients. The concentrations of circulating C4, C3 and properdin varied less consistently according to disease activity. The concentrations of serum properdin were never found to be low, which was in contrast to the finding of reduced properdin uptake by solid phase IC in most of the samples.
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PMID:Complement fixation by solid phase immune complexes. Reduced capacity in SLE sera. 326 27

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