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)

Immunochemical properties of monoclonal autoantibodies to single stranded DNA (ssDNA), which were derived from systemic lupus erythematosus (SLE) prone mice and were specific for poly(dG), were studied using a hapten inhibition assay with oligo- and mononucleotides. Deoxyguanosine monophosphate (dGMP) completely inhibited the ssDNA binding of poly(dG) specific monoclonal antibodies. The affinity to deoxyguanosine was approximately 70% of dGMP, and to guanosine monophosphate (GMP) and to guanosine was 38% and 24%, respectively. In contrast, other purine monomers such as deoxyadenosine monophosphate (dAMP), adenosine monophosphate (AMP) and adenosine exhibited virtually no inhibitory effect on the ssDNA binding of these monoclonal hybridoma autoantibodies. By the same competitive inhibition enzyme immunoassay using deoxyguanosine oligonucleotides of various chain lengths, the minimal antigenic size of ssDNA encompassed by the combining site of the Fab portion of anti-ssDNA monoclonal autoantibodies was determined to be the tetra- or pentanucleotide.
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PMID:Specificity of mouse hybridoma antibodies to DNA. III. Antigenic determinants of nucleic acids recognized by poly(dG) specific monoclonal antibodies. 240 2

An enzyme-linked immunosorbent assay (ELISA) was utilized to characterize nucleotide-reactive antibodies present in the sera of 67 human subjects: 27 active SLE, 20 inactive SLE, and 20 asymptomatic controls. This assay consisted of measuring the quantity of antibodies retained by a panel of immobilized 5'-nucleotide-BSA conjugates (AMP-, GMP-, CMP-, UMP-, and TMP-BSA) together with ssDNA and dsDNA antigens. Although the relative distribution of antibodies binding to nucleotide-BSA antigens (i.e., anti-GMP greater than anti-AMP greater than or equal to anti-TMP greater than anti-UMP greater than or equal to anti-CMP antibodies) was independent of clinical status, the sera of active SLE patients possessed three- and five-fold higher concentrations of these antibodies relative to those present in inactive SLE and control subjects, respectively. Affinity purification of the most dominant of these antibody populations with DNA- and GMP-agarose adsorbents suggested that the majority of anti-GMP antibodies were monospecific with respect to the guanine base moiety. For example, antibodies retained by GMP-agarose reacted with GMP-BSA and ssDNA but not with other nucleotide-BSA or dsDNA antigens. However, ELISA competition-inhibition studies with affinity-purified anti-GMP antibodies indicated that although the guanine base represents an important determinant, guanine-enriched oligo- and polynucleotides were preferred substrates (i.e., guanine-dependent, oligonucleotide specificity). This was exemplified by the finding that a 500- and 50-fold molar excess of dGMP and d(G)4 were required to achieve the same degree of inhibition as that observed with d(G)8. Finally, and as evaluated by indirect immunofluorescence with fixed HEp-2 cells, affinity-purified anti-GMP antibodies reacted with antigens restricted to nucleolar organelles.
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PMID:Distribution and specificity of nucleotide-reactive autoantibodies in human SLE. 329 28