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)

RHP has been purified from the plasma of both normal individuals and patients with rheumatoid arthritis (RA). RHP from both these sources was shown to be identical with Factor H by reaction with antisera and N-terminal amino acid sequence analysis. Factor H, from both normal and RA sera, inhibited the solubilization of immune precipitates but did not affect prevention of immune precipitation. Factor H was shown to inhibit the haemolytic activity of fluid-phase C1, but unlike C1-inhibitor, it had little effect on C1 bound to EA (EAC1). Factor H was shown to complex with intact C1, to isolated C1q and to the C1r:C1s tetramer. However, binding of factor H to C1 did not dissociate the C1 macromolecule. A C1-Factor H complex was detected in the serum and plasma from normal individuals and patients with systemic lupus erythematosus and RA. Serum levels of this complex were reduced, by EDTA-treatment of serum and by activation of complement by the classical pathway.
 ...
PMID:Purification and characterization of RHP (factor H) and study of its interactions with the first component of complement. 138 42

Complexes formed by the interaction of negatively charged phospholipids and beta 2-glycoprotein I (beta 2-I) are the target of autoantibodies in systemic lupus erythematosus. The highly positively charged fifth (C-terminal) domain of human beta 2-I was produced as a fusion protein in an Escherichia coli expression system and was shown to bind to the negatively charged phospholipid, cardiolipin, almost as well as the intact protein. In an attempt to define the 3D structure of this domain, the disulphide linkage pattern was determined and shown to be Cys 1-4, Cys 2-5 and Cys 3-6 in contradiction to an earlier report. In the light of this information, the sequence of the fifth domain of beta 2 I (beta 2-I-5) is readily aligned with that of the 16th repeat of factor H, of which the 3D structure is known, and a model of beta 2I-5 has been built by homology. On the basis of the model we suggest residues that might be the target of profitable site-directed mutagenesis in structure-function studies.
 ...
PMID:Activity, disulphide mapping and structural modelling of the fifth domain of human beta 2-glycoprotein I. 142 88

The platelet glycoprotein (GP) IIb-IIIa complex figures prominently as an immunogen in autoimmune (idiopathic) thrombocytopenic purpura (ITP). 2E7 is a human monoclonal IgM autoantibody, derived from splenocytes of a patient with ITP, that recognizes a specific octapeptide amino acid sequence, Phe-Asp-Gly-Tyr-Trp-Gly-Tyr-Ser, on the heavy chain of GPIIb. This represents the first precise identification of an epitope on GPIIb-IIIa recognized by a human antibody. In this study, we have isolated total mRNA from 2E7, synthesized the corresponding cDNA using reverse transcriptase, and amplified the immunoglobulin mu and kappa chain cDNA by the Taq 1 polymerase chain reaction (PCR) using specific primers. The 2E7 mu chain variable region is encoded by a VH3 gene segment that is 98% homologous to the germline gene VH1.9III, a D-gene that is not homologous to any of the germline D-genes reported to date, and a JH6 gene segment that is essentially germline. The heavy-chain sequence, save for the unique D-gene, is similar to that of a number of human autoantibodies. The 2E7 kappa variable region is encoded by a Vk1 gene segment linked to a Jk1 gene segment. The Vk1 sequence of 2E7, with the exception of one nucleotide, is identical to that of autoantibody HF2-1/17, a prototype of SLE-associated anti-DNA autoantibodies bearing the 16/6 idiotype. The single base substitution results in a relatively conservative exchange of Asp for Glu at position 70 of the protein sequence. Despite this near identity in sequence, 2E7 does not bind to either single-stranded or double-stranded DNA. From these results, we conclude that specificity of 2E7 is likely to reside in either or both the D-JH region (CDR3) of the mu chain and the Jk region (CDR3) of the kappa chain. In addition to the identification of a novel D-gene, we also provide evidence that the 2E7 VHIII gene is probably a prototype of a VHIII subfamily, that the germline Vk1 gene shared by 2E7 and autoantibodies of the 16/6 idiotype probably represents a separate Vk family, and that this Vk gene cannot itself attribute specificity for DNA.
 ...
PMID:Nucleotide sequence of the human autoantibody 2E7 specific for the platelet integrin IIb heavy chain. 171 98

The human monoclonal autoantibody HF2-1/17, produced by a human-human hybridoma derived from lymphocytes of a lupus patient with thrombocytopenia, reacts with single stranded DNA and platelets. To determine the chemical nature of the autoantigen against which this antibody is directed on platelets, this platelet antigen was purified by the lipid extraction of sonicated platelets, DEAE-Sephadex chromatography, and high performance liquid chromatography. The purified glycolipids, a trace component in platelets, demonstrated high reactivity with the HF2-1/17 antibody using a competition enzyme-linked immunosorbent assay system or immunostaining of thin layer chromatograms. The purified glycolipids co-migrated with bovine sulfatides by thin layer chromatography. The purified glycolipids contain sulfate and galactose but not sialic acid or phosphate. Fast atom bombardment-mass spectrometry revealed these sulfatides to be sulfated monohexyl ceramides. The dominant species has a molecular weight of 794 while a minor form has a molecular weight of 812 due to an extra hydroxyl group and loss of a double bond. These results indicate that the platelet autoantigen against which the human monoclonal anti-DNA antibody is directed represents a family of novel monogalactosyl sulfatides.
 ...
PMID:Sulfated glycolipids are the platelet autoantigens for human platelet-binding monoclonal anti-DNA autoantibodies. 186 60

The complete amino acid sequences of the variable regions of the heavy and light chains of a human IgM monoclonal platelet-binding autoantibody have been determined. This antibody, HF2-1/17, produced by a human x human hybridoma prepared from lymphocytes of a patient with systemic lupus erythematosus and thrombocytopenia, is polyreactive with single-stranded DNA, synthetic polynucleotides, sulfated carbohydrates, and acidic glycolipids isolated from platelet membranes. The heavy chain is of the VHIII subgroup, and the light chain is of the VKI subgroup. The heavy chain is the expression product of the VH26 germline gene. The light chain bears significant homology to other immunoglobulins of known primary structure, including WEA, GAL, HAU, HK101, and DEE. These results suggest that HF2-1/17 may be an autoantibody derived with little or no modification from germline genes. A model of the antibody combining site suggests that arginine 24 and arginine 30 in the light chain (CDR1) interact with a surface defined by phosphate or sulfate groups of the antigen.
 ...
PMID:Amino acid sequence of a platelet-binding human anti-DNA monoclonal autoantibody. 250 2

The complement (C) system consists of two activation pathways, the classical and the alternative, which may both be activated by immune complexes (IC). C activation products become attached to the IC during activation leading to profound changes in the properties of the complexes. The common terminal C pathway is not involved in activation mediated by fluid phase IC. The interaction between IC and C may lead to: 1) Increased solubility of the IC. 2) Enhanced phagocytosis and clearance of the IC. 3) Altered tissue distribution of the IC. 4) Generation of soluble C fragments which mediate inflammation. 5) Tissue damage by activation and/or lysis of bystanding cells. 6) Modulation of B-cell proliferation and differentiation. Activation of the C system by IC is an essential normal component in the clearance of invading foreign material. However, in conditions with a persistent high concentration of IC in the circulation or tissues, this activation may lead to chronic inflammatory disease. This thesis reviews certain aspects of the interactions between IC and C. The earlier work describes our development of an assay for measuring the C activity in patient sera by its ability to solubilize preformed, fluid phase IC (CMS assay). The CMS was found to be dependent upon the alternative pathway of C and facilitated by the classical. Further studies concerning the influence of C deficiencies or depletion of C factors, the concentration of divalent metallions, the temperature and the ionic strength were performed to characterize the reaction. The CMS assay, showed that serum from patients with SLE and other systemic persistent inflammatory diseases and infections exhibited a reduced capacity to solubilize IC. The CMS values correlated inversely to the disease activity in SLE patients. It was also for the first time demonstrated that serum from some SLE patients contained a CMS inhibitor and it is suggested that this inhibitor of CMS is endogenously formed incompletely C solubilized IC. This suggestion is based upon several lines of indirect evidence, and by HPLC size distribution analysis of the IC in SLE sera, which showed a reduction in IC size upon incubation with C. A negative correlation between the CMS capacity and the content of CMS inhibitory material was found. The CMS capacity did not correlate to the serum concentration of any of the C factors C3b/C3c, C4, Clq, factor B, factor H or factor I, nor did it correlate to the concentration of the degradation product C3dg. But a low concentration of one of the native C factors was associated with a reduced CMS.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Immune complex modulation by plasma proteins. With special reference to the complement system and autoimmune diseases. 253 63

Erythrocyte complement receptor type 1 (CR1) was measured in 71 patients with systemic lupus erythematosus (SLE) and 43 healthy controls. The level of erythrocyte CR1 in patients with SLE was significantly lower than that of controls and correlated with the disease activity of SLE. The more active the disease, the greater the decrease in erythrocyte CR1. The level of erythrocyte CR1 was inversely correlated with the level of circulating immune complexes (CIC) and was positively correlated with C3, CH50, factor B, and factor H. We also found lupus nephritis more frequently in patients with decreased erythrocyte CR1 than in those with normal levels of erythrocyte CR1. Our results suggest that the deficiency of erythrocyte CR1 in patients with SLE is acquired and may serve as a variable of clinical disease activity and may play a role in the pathogenesis of SLE.
 ...
PMID:Erythrocyte complement receptor type 1 in patients with systemic lupus erythematosus. 281 Feb 56

Activation of the complement cascade leads to the generation of multiple breakdown products which bind on to specific cellular receptors and regulate their function. In this review, we describe the biochemical and physiological features of the 7 known complement receptors. Four of them (complement receptors 1, 2, and 3 and receptors for C3a) bind cleavage fragments of the third component of the complement and three have specificity for C1q, factor H and C5a. In patients with systemic lupus erythematosus, a unique human autoimmune disorder, the numbers of CR1 on the surface of the red blood cells are decreased; in this review we discuss the implications in the pathogenesis of SLE. A number of patients have now been reported whose cells lack CR3 from their surface; this deficiency is associated with a number of immune cell dysfunctions which are discussed in detail. Finally, we discuss aberrations in the expression of complement receptors in certain human leukemic cells.
 ...
PMID:The biology and pathophysiology of complement receptors. 294 15

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.
 ...
PMID:Combined homozygous factor H and heterozygous C2 deficiency in an Italian family. 296 9

Rapid progress has been made recently on the elucidation of the structural components of the complement system by the application of recombinant DNA techniques. The derived amino acid sequences of most of the complement proteins are now available through cDNA cloning, and significant progress has been made in the discovery of the genetic organization of the corresponding genes. The linkage of some of the complement component genes has been established through the study of phenotypic genetics. Of particular interest has been the mapping of two clusters of genes which encode proteins involved in the activation of C3. C2, C4 and factor B, three of the structural components of the classical and alternative pathway C3 convertases, are encoded by genes which map to the MHC on human chromosome 6. The linkage of the genes with each other in a 100 kb segment of DNA has been established through the isolation of overlapping cosmid clones of genomic DNA, and PFGE has defined the molecular map position of these genes within the class III region of the MHC. The regulatory proteins factor H, C4BP, CR1 and DAF, which are involved in the control of C3 convertase activity, are encoded by closely-linked genes (termed the regulators of complement activation or RCA linkage group) that have been mapped to human chromosome 1. PFGE has defined the linkage of the CR1, C4BP and DAF genes, together with the CR2 gene in an 800 kb segment of DNA, and it is clear that this technique will eventually be applied to the molecular mapping of other complement genes in relation to their flanking loci. Polymorphism is a feature of many of the complement proteins, especially those encoded by genes in the MHC class III region. Of these, C4 is by far the most polymorphic, and differences in gene size and gene number, in addition to the functional and antigenic differences in the gene products, have been recognized. Null alleles at either of the C4 loci are rather common and may be important susceptibility factors in some HLA-associated diseases, particularly SLE. The molecular basis of complement deficiency states has begun to be elucidated. In many cases, the deficiency is not caused by a major gene deletion or rearrangement, and techniques which detect single point mutations in DNA (Cotton et al, 1988) will have to be applied to fully characterize the nature of the defect.
 ...
PMID:The molecular genetics of components of the complement system. 306 64


1 2 3 4 5 Next >>