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)

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.
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PMID:Amino acid sequence of a platelet-binding human anti-DNA monoclonal autoantibody. 250 2

A 47-year-old man with Graves' disease suffered from a feeling of hunger and sweating in the night, polyarthralgia and fever one month after the start of treatment with methimazole. The above symptoms were ascribed to the side effects of methimazole; insulin autoimmune syndrome and lupus-like syndrome. The change in the antithyroid drug to propylthiouracil caused an amelioration of the symptoms. In addition to an anti-insulin antibody with a high binding capacity, hyperglucagonemia (260 pg/ml with a plasma glucose level of 61 mg/dl) was observed, which returned to normal in parallel with the decrease in the insulin binding capacity of the plasma one month after beginning the treatment with propylthiouracil. A normal decrease in the plasma glucagon level due to exogenous insulin (2 mU/kg/min) was observed with the euglycemic clamp. However, the plasma glucagon level was not suppressed by the oral glucose loading and elicited a poor response to the arginine infusion. Taking previous reports into account, this basal hyperglucagonemia seems to be a characteristic finding in the insulin autoimmune syndrome, while a sluggish response of glucagon to oral glucose or arginine infusion might be ascribed to hyperthyroidism. This is the first case report concerning a kinetical study of the glucagon secretion in insulin autoimmune syndrome with Graves' disease.
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PMID:Hyperglucagonemia of insulin autoimmune syndrome induced by methimazole in a patient with Graves' disease. 265 8

A 60 kDa calcium-binding protein (CBP) was purified from canine brain and its N-terminal sequence determined to be: Glu-Pro-Ala-Ile-Tyr-Phe-Lys-Glu-Gln-Phe-Leu-Asp-Gly-Asp-Gly-X-Thr-Arg-X- Ile- Glu-Ser-Lys. This sequence is very similar to that of "Ccalregulin", a CBP of unknown function which is similar in size and appears to be present in most animal tissues. An unexpected and even more striking similarity was found with the N-terminal sequence of the human Ro/SS-A antigen, a 60 kDa protein which has long been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus. These findings suggest that the Ro/SS-A antigen is probably also a CBP.
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PMID:Sequence homology of a canine brain calcium-binding protein with calregulin and the human Ro/SS-A antigen. 280 21

Measurements of complement components in sera from patients with systemic lupus erythematosus (SLE) and some of their relatives indicated that decreased levels of CH50, C4 and C2 were mostly related to a genetic deficiency at one or both of the loci coding for C4, at least in those patients in whom decreased C4 levels were associated with normal C1 hemolytic activity. C4 deficiency is either isolated or associated with complement activation. In some patients with C4 deficiency, complement activation could only be demonstrated by measuring plasma level of the C3 cleavage fragment, C3a des Arg. Decreased concentration and/or hemolytic activity of C4 and C2 in SLE cannot be used to assess the activity of the disease.
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PMID:[Components of the classical complement pathway in systemic lupus erythematosus]. 295 Apr 98

Bradykinin is degraded in human plasma by a carboxypeptidase to yield desArg9-bradykinin (DBK) which is then digested by angiotensin-converting enzyme (ACE) to the pentapeptide Arg-Pro-Pro-Gly-Phe and the tripeptide Ser-Pro-Phe. We have studied the rate of kinin degradation by each of these enzymes in patients with rheumatoid arthritis (RA) and with systemic lupus erythematosus (SLE), compared with the degradation rate in degenerative joint disease and normal subjects. Carboxypeptidase activity was the same in all individuals, but ACE activity was increased in the RA and SLE patients. We examined the effects of aspirin, sodium salicylate, auranofin, penicillamine, and corticosteroids on kinin metabolism, and all of these were marked inhibitors of ACE; however, only penicillamine had any demonstrable inhibition of carboxypeptidase. These observations suggest rapid degradation of DBK in patients with untreated RA and SLE, whereas drugs utilized in therapy have the opposite effects. Studies to examine the role of DBK in disease manifestations are in progress.
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PMID:Assessment of kininases in rheumatic diseases and the effect of therapeutic agents. 303 Mar 35

Antibodies to the Sm-D polypeptide antigen are closely associated with the rheumatic disease systemic lupus erythematosus. Sm-D exists in the cell as one of the core proteins of the small nuclear ribonucleoprotein complexes implicated in RNA processing. We have isolated a cDNA clone, D45-2, coding for the Sm-D human nuclear antigen by screening a human B-lymphocyte cDNA library with synthetic oligonucleotide probes. The 1633-base-pair clone contains an open reading frame (ORF) 357 nucleotides long, capable of encoding a 13,282-dalton polypeptide. The Sm-D coding region is initiated at an AUG codon downstream from a sequence with excellent match to the consensus for the eukaryotic ribosome-binding site. The Sm-D ORF is preceded by a 150-nucleotide-long untranslated leader and followed by a 1126-nucleotide-long untranslated region containing four putative poly(A) signals. The predicted amino acid sequence reveals a (Gly-Arg)9 repeated motif at the C terminus, which may constitute one of the Sm-D immunoreactive determinants. Moreover, this C terminus shows interesting features: (i) a good homology to protamines as expected for a nucleic acid binding protein and (ii) a striking similarity to a region in the Epstein-Barr nuclear antigen.
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PMID:Molecular cloning of a cDNA encoding the human Sm-D autoantigen. 326 Mar 84

Serum and plasma from patients with active systemic lupus erythematosus contain a specific inhibitor of complement (C5)-derived chemotactic activity. We found that the inhibitor is antigenically related to the Bb fragment of complement factor B. Lupus plasma and purified inhibitor significantly reduced the chemotactic activity of zymosan-treated normal serum, an effect that was abolished by antibodies to factor B. Similar results were obtained when purified Bb was used. Neither purified inhibitor nor Bb inhibited the chemotactic activity of purified human C5a or C5a des Arg. As reported previously, the chemotactic activity of C5a des Arg was enhanced significantly by the addition of an anionic polypeptide (cochemotaxin) present in normal serum and plasma. Interestingly, both purified lupus inhibitor and Bb inhibited the chemotactic activity exhibited by mixtures of C5a des Arg and its cochemotaxin. This effect was due, most likely, to their ability to neutralize the enhancing effect of the cochemotaxin on the chemotactic activity of C5a des Arg. Immunoelectrophoresis and western blots revealed that the purified inhibitor reacted with anti-factor B and exhibited a similar charge and molecular weight as purified Bb.
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PMID:Specific inhibitor of complement (C5)-derived chemotactic activity in systemic lupus erythematosus related antigenically to the Bb fragment of human factor B. 364 93

In previous work a polyclonal B cell activator has been detected in the serum of patients with rheumatoid arthritis (RA). This activator is associated with alpha 2-macroglobulin (alpha 2M) and its activity is blocked by low-Mr trypsin inhibitors, which suggests that it may be a protease-alpha 2M complex. Here we determined the possibility of developing a routine clinical chemistry test for detection of this complex in patients' blood. We measured with chromogenic substrates the total proteolytic activity of citrated plasma and of the alpha 2M immunoabsorbed from plasma. Low-Mr substrates containing Arg were degraded much better by plasma from RA patients than by plasma from patients with other arthritides. Low-Mr substrates containing Leu, Lys, or Gly or the large-Mr substrate Azocoll were not degraded by RA patients' plasma. alpha 2M from RA patients' plasma attached to a solid-phase immunoabsorbent degraded an Arg-containing tripeptide much better than did the alpha 2M from normal donors, from patients with systemic lupus erythematosus, or from those with joint inflammation of other, "non-autoimmune" origin. Although the enzyme associated with alpha 2M in the plasma from RA patients appeared to be similar to trypsin, the differences in optimal pH, cation concentration, degradation of Lys-containing substrates, and biological activity suggest otherwise. We speculate that the alpha 2M-protease complexes are generated in the immune system and contribute to the inflammatory and autoimmune phenomena in RA.
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PMID:Detection of alpha 2-macroglobulin-associated proteases in the plasma of patients with rheumatoid arthritis. 620 92

The human C3b receptor (C3bR) is a glycoprotein that exists in two allotypic forms having Mr values of approximately 250,000 (F) and 260,000 (S). The number of receptors present on erythrocytes varies by eightfold among normal individuals and is genetically regulated by two codominant alleles that are distinct from the alleles determining the structural polymorphism. C5a and C5ades Arg induce rapid increases in the number of receptors expressed by neutrophils in vitro, and probably account for the increased receptor expression on neutrophils in patients undergoing hemodialysis. Cytoskeletal association of the C3bR on monocytes and neutrophils is suggested by experiments demonstrating receptor-mediated phagocytosis and adsorptive endocytosis through coated pits, and by the reciprocal coredistribution of cross-linked C3b and Fc receptors and the detergent insolubility of cross-linked C3bR. The factor H-like cofactor activity of the C3bR promotes the cleavage of bound C3b to iC3b, C3c, and C3d,g, which may enhance the clearance of circulating immune complexes and the generation of ligands for CR2 and CR3. The inherited partial deficiency of the erythrocyte C3bR in patients with systemic lupus erythematosus and the absence of glomerular C3bR in these patients with proliferative glomerulonephritis may contribute to systemic and organ-specific abnormalities in the clearance of immune complexes in this disease.
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PMID:Structure and function of the human C3b receptor. 623 86

We characterized three monoclonal antibodies with histone reactivity which were derived from spleen cells obtained from unmanipulated NZB/NZW or MRL/1 mice. By using an enzyme-linked immunosorbent assay, we noted that all three antibodies reacted with chromatin histones as well as with total histones extracted from chromatin. None of the antibodies appeared to require DNA as part of the antigen. One antibody (BWH-1) recognized a determinant present in the nucleosome core H2A-H2B complex but showed little reactivity with any of the individual histones (H1, H2A, H2B, H3, or H4). In contrast, the other two monoclonal antibodies each recognized multiple individual histones in a unique pattern. Antibody MH-1 reacted with H2A, H2B, and H3; antibody MH-2 reacted with H2A, H3, and H4. MH-1 demonstrated cross-reactivity with poly-1-lysine but not poly-1-arginine or protamine sulfate; the opposite pattern of cross-reactivity was observed with MH-2. The antigenic determinants recognized by MH-2 were all trypsin-sensitive, suggesting that these determinants were present on the N-terminal regions of the respective individual histones. These studies revealed markedly different specificities of anti-histone monoclonal antibodies derived from murine models of systemic lupus erythematosus. These and other similarly derived antibodies may provide interesting tools to understand the specificity and biologic importance of anti-histone autoantibodies in different diseases.
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PMID:Monoclonal anti-histone autoantibodies derived from murine models of lupus. 633 55


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