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 antigen-binding specificity of human hybridoma-derived monoclonal autoantibodies (mAb) was analysed with mAbs derived from the spleens of two patients with active systemic lupus erythematosus (SLE). From one patient 72 mAbs (RSP clones) and from the other 173 mAbs (RT clones) were obtained. The binding specificity of these mAbs was analysed by solid- and fluid-phase ELISA against the autoantigens ssDNA, dsDNA, cardiolipin, SmRNP, histones, Sm-D and SS-B (La) synthetic peptides, and foreign antigens including bacterial polysaccharides. In addition, antinuclear antibody activity and anti-dsDNA binding were confirmed by fluorescence staining methods. Reflecting the patient's serological profile, none of the antibodies from the RSP clones reacted with ssDNA or dsDNA but 12 reacted with cardiolipin. In addition, three mAbs reacted with H4, five with U1 RNP, two with Sm-D peptides and 12 with SS-B peptides. In contrast, from the RT fusion, nine mAbs reacted with ssDNA, HI and SS-B peptides, seven with cardiolipin, four with dsDNA, two with Sm-D peptides and one each with H2A, H3 and H4. In many cases one mAb showed reactivity with more than one antigen: for example, mAb RT 72 binds to ssDNA, dsDNA, cardiolipin, H1, H4 and an Sm-D peptide; RT 6 binds to H1, SmRNP and ubiquitinated histone H2A. However, none of the antibodies showed 'across the board' polyreactivity; indeed, the selectivity of the reactions was notable and marked variation in antibody affinity was recorded. Eight of the mAbs bound to Salmonella typhimurium and two to the Klebsiella polysaccharide K-30.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupus 1992 May
PMID:Antigen-binding diversity of human hybridoma autoantibodies derived from splenocytes of patients with SLE. 130 76

ELISA quantitation of antibodies to Klebsiella pneumonia, Proteus mirabilis, and Yersinia enterocolitica was conducted in 75 ankylosing spondylitis (AS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) probands and in 262 of their first-degree relatives. The control group comprised 28 healthy donors. Sixteen (64 per cent) AS probands (12 with B27+) and 26 (30.2 per cent) their relatives (14 with B27+) were found to have high titres of antibodies to Klebsiella pneumonia. In 18 (60 per cent) active RA probands and 27 (23.7 per cent) relatives, antibodies to Proteus mirabilis were found. The obtained results suggest the presence of genetic determinants of the increased immune response to various infectious agents, at least in the AS cases. The possibility of Enterobacteriaceae acting as polyclonal stimulators is not excluded.
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PMID:[Circulation of intestinal infection in the families of patients with rheumatic diseases and the state of humoral immunity to enterobacterial antigens]. 277 62

The functional affinity and IgG subclass of antibodies to ss and dsDNA were measured by ELISA in five serial samples from 41 patients with systemic lupus erythematosus (SLE) who were divided into relatively homogeneous disease subgroups. Anti-dsDNA antibodies were restricted to IgG1 and IgG3 in renal disease and levels increased with disease severity. Functional affinity of IgG1 and IgG3 anti-dsDNA fell in patients with severe renal disease, suggesting that the high affinity antibody population lost from the serum was localizing in the kidneys. IgG2 anti-dsDNA were found in patients with joint and skin disease alone and in the thrombotic/spontaneous abortion subgroup. IgG2 antibody levels did not correlate with disease severity but did correlate with the presence of antibodies to Klebsiella K30 and may have represented a cross-reactive antibody population.
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PMID:Serial studies of the IgG subclass and functional affinity of DNA antibodies in systemic lupus erythematosus. 307 12

Patients with systemic lupus erythematosus were examined for the presence of serum antibodies reactive with phospholipids (PL) extracted from the membranes of Klebsiella K30 (K30PL). Affinity-purified anti-K30PL antibodies were tested for their ability to cross-react with other PL antigens or DNA and for the presence of idiotypic markers known to be associated with anti-DNA antibodies or antibodies to Klebsiella K30 polysaccharide (K30p). Affinity-purified antibodies to K30PL, phosphatidylserine (PS), or phosphatidylinositol (PL) uniformly cross-reacted with each other. Analysis of the PL preparations by thin-layer chromatography and reversed-phase high-performance liquid chromatography (HPLC) showed the presence of several components. Lupus sera reacted with one component mainly in the HPLC-fractionated K30PL preparation, although this component appeared to be present in the other PL preparations. Direct-binding and inhibition studies showed that affinity-purified antibodies to the K30PL extract, PS, or PI reacted poorly with DNA. However, the anti-K30PL antibodies possessed a prominent anti-DNA idiotypic marker (AM Id) in 61% of the patients and an anti-K30p idiotypic marker (SP Id) in 94% of the patients. The results thus show that anti-K30PL antibodies are idiotypically related to anti-DNA and anti-K30p antibody subpopulations, although they do not share the same antigen-binding characteristics.
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PMID:Anti-Klebsiella K30 phospholipid antibodies in systemic lupus erythematosus: antigen cross-reactions and idiotypic sharing with antibodies to DNA and Klebsiella K30 polysaccharide. 326 36

Cold agglutinin disease is a normo- or macrocytic anemia due to antibodies, active under body temperature, mostly belonging to the immunoglobulin class M. Initially the agglutination of erythrocytes with acrocyanosis is reversible at body temperature. High antibody activity or long lasting period of coldness lead to intravascular or intrahepatic hemolysis, but high risk anemia is rare. Beside the idiopathic form, infection induced (especially infectious mononucleosis, cytomegalovirus, Mycoplasma pneumoniae, Klebsiella), and drug induced (especially quinidine, alpha methyldopa, penicillin, para-aminosalicylic acid, various analgetics, sulfonylurea), tumor associated (especially malignant lymphomas), and autoimmune disease associated (especially systemic lupus erythematosus) cold agglutinin anemias are discribed. "Cross reacting antigenity" to the hemolysing agent and the membrane of erythrocyte, exogenous induced changing of erythrocytic antigenity, and diversification concerning the production of antibodies are discussed as pathophysiological explanations.
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PMID:[Cold agglutinin disease]. 328 90

Recent studies have indicated that both ankylosing spondylitis and the anti-DNA antibodies found in systemic lupus erythematosus may be related to Klebsiella surface antigens. In order to explore these possible relationships further, the sera of 24 patients with ankylosing spondylitis (AS), and 20 controls, have been examined for binding to a wide range of antipolynucleotide antibodies, antibodies binding to the Klebsiella pneumoniae polysaccharide K30 and two DNA antibody idiotypes designated 16/6 and 134. We report that although 21% of the AS patients had IgG ssDNA antibodies it is evident that the aetiopathogenesis of this disease is not through the mechanism of autoantibodies or the common DNA antibody idiotypes tested.
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PMID:A study of antipolynucleotide antibodies, anti-Klebsiella (K30) antibodies and anti-DNA antibody idiotypes in ankylosing spondylitis. 349 12

The NH2-terminal amino acid sequences have been determined by automated Edman degradation for the heavy and light chains of five monoclonal IgM anti-DNA autoantibodies that were produced by human-human hybridomas derived from lymphocytes of two patients with systemic lupus erythematosus. Four of the antibodies were closely related to the idiotype system 16/6, whereas the fifth antibody was unrelated idiotypically. The light chains of the 16/6 idiotype-positive autoantibodies (HF2-1/13b, HF2-1/17, HF2-18/2, and HF3-16/6) had identical amino acid sequences from residues 1 to 40. Their framework structures were characteristic of VKI light chains. The light chain of the 16/6 idiotype-negative autoantibody HF6-21/28 was characteristic of the VKII subgroup. The heavy chains of the 16/6 idiotype-positive autoantibodies had nearly identical amino acid sequences from residues 1 to 40. The framework structures were characteristic of the VHIII subgroup. In contrast, the GM4672 fusion partner of the hybridoma produced small quantities of an IgG with a VHI heavy chain and a VKI light chain. The heavy chains of the lupus autoantibodies and the light chains of those autoantibodies that were idiotypically related to the 16/6 system had marked sequence homology with WEA, a Waldenstrom IgM that binds to Klebsiella polysaccharides and expresses the 16/6 idiotype. These results indicate a striking homology in the amino termini of the heavy and light chains of the lupus autoantibodies studied and suggest that the V regions of the heavy and light chains of the 16/6 idiotype-positive DNA-binding lupus auto-antibodies are each encoded by a single germ line gene.
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PMID:Homology of the NH2-terminal amino acid sequences of the heavy and light chains of human monoclonal lupus autoantibodies containing the dominant 16/6 idiotype. 392 67

Six monoclonal IgM from patients with Waldenstrom's macroglobulinemia that react with Klebsiella polysaccharides were tested for their ability to bind to nucleic acid antigens. One of the macroglobulins bound to the polynucleotide poly(G), and one bound to poly(G), poly(I), and single-stranded DNA. The reaction with the polynucleotides was specifically inhibited by the Klebsiella polysaccharide K30. A monoclonal lupus anti-DNA antibody (16/6) was found to react weakly with the Klebsiella polysaccharides K30 and K21. Five of the Waldenstrom macroglobulins shared an idiotypic determinant with the 16/6 anti-DNA antibody. The reaction between the macroglobulins and the antiidiotype serum was specifically inhibited by Klebsiella polysaccharides, an indication that the idiotypic marker was in the antigen-binding site of the macroglobulins. These results indicate the existence of widely dispersed conserved variable region genes that encode idiotypically related immunoglobulins with the capacity to bind to both bacterial polysaccharides and nucleic acids. Such genes can be expressed by patients with either Waldenstrom's macroglobulinemia or systemic lupus erythematosus.
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PMID:Immunochemical similarities between monoclonal antibacterial Waldenstrom's macroglobulins and monoclonal anti-DNA lupus autoantibodies. 392 65

Two human IgM lambda monoclonal antibodies (MAb) derived from the splenic lymphocytes of patients with idiopathic thrombocytopenia (Ben) and systemic lupus erythematosus (Wri) were studied. BEN-27 and WRI-170 hybridoma supernatants were screened for binding to ssDNA, dsDNA, poly (ADP-ribose), cardiolipin, histone subclasses and Klebsiella K30 cell wall antigen. Of this panel of antigens, BEN-27 and WRI-170 antibodies reacted only with histone H1. Their fine specificity was defined by direct and inhibition ELISA with synthetic peptides of the major human H1b variant. Antibody WRI-170 was shown to bind to both the N- and C-terminal peptides encompassing residues 1-16 and 204-218 of H1b whereas BEN-27 reacted only with peptide 204-218. To analyse the genetic origin of these autoantibodies, we determined the nucleotide sequence of the heavy (H) and light (L) chain variable regions of these two hybridomas. BEN-27 and WRI-170 MAbs were found to use VH1-DN1-JH4/V lambda 3-J lambda 2 and VH3-DIR2-D21/9-JH1/V lambda 2-J lambda 2 gene segment combinations respectively. Between 70 and 95% homology was demonstrated when the mRNA sequences for BEN-27 and WRI-170 were compared with published VH and V lambda germline sequences. This finding suggests that BEN-27 heavy and light chains and WRI-170 light chain use unidentified VH and V lambda germline gene segments whereas WRI-170 heavy chain derives from a VH gene segment recently identified. It is noteworthy that the CDRs of the two MAbs contain several negatively charged amino acids which are assumed to be of critical importance in antigen binding. Moreover, striking similarities are observed between BEN-27 heavy chain CDR2 and a previously described murine anti-H1 Ab heavy chain CDR2.
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PMID:Sequence analysis and fine specificity of two human monoclonal antibodies to histone H1. 751 Dec 11

The production of antibodies to Klebsiella capsular polysaccharides was measured in sera from either HLA-B27-positive (HLA-B27+) or HLA-B27-negative (HLA-B27-) patients with classical ankylosing spondylitis (n = 54). These sera were compared with sera from patients with various rheumatic diseases (n = 82) and HLA-B27+ or HLA-B27- healthy individuals (n = 85). All sera were analyzed by means of an enzyme-linked immunosorbent assay specific to each of the 77 Klebsiella serotypes. The sera from HLA-B27+ patients with ankylosing spondylitis showed a significantly higher antibody frequency to the capsular types K26, K36, and K50 than the sera from HLA-B27- ankylosing spondylitis patients, patients with psoriatic arthritis, systemic lupus erythematosus, rheumatoid arthritis, or reactive arthritis after Yersinia enterocolitica infection, or healthy controls (P < 0.02). The antibodies were of the immunoglobulin G type. No significant antibody response to the other 74 Klebsiella serotypes, noncapsulated mutants of K26, K36, and K50, or preparations of Citrobacter, Serratia, Hafnia, or Morganella spp. or Streptococcus pneumoniae could be detected. The results might suggest a specific association between these capsular types and HLA-B27+ ankylosing spondylitis and might imply their predominance in this disease.
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PMID:Comparison of the antibody responses to the 77 Klebsiella capsular types in ankylosing spondylitis and various rheumatic diseases. 792 63


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