Lovorka Stojanov

University of North Carolina at Chapel Hill, North Carolina, United States

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Publications (4)14.88 Total impact

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    ABSTRACT: To examine humoral immune responses to the native Ku antigen and to evaluate the role of autoantibodies in stabilizing intermolecular contacts between the p70 and p80 Ku subunits. Recombinant free human p70 and p80 Ku subunits and p70/p80 heterodimers were expressed in Sf9 (insect) cells using baculovirus vectors. Affinity-purified recombinant human p70, p80, and p70/p80 dimer were studied by enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation to evaluate autoantibody specificities in sera from 58 patients with systemic autoimmune disease. Anti-Ku antibodies were detected by ELISA or immunoprecipitation using K562 cell Ku antigen. All of the sera were reactive with the native recombinant p70, p80, or p70/p80 antigens: 47% were anti-p70+,anti-p80+ and 32% were anti-p70-,anti-p80+, but only 3% were anti-p70+,anti-p80-. Unexpectedly, 18% of the sera recognized the p70/p80 dimer but did not recognize native p70 or p80 alone. A subset of sera containing autoantibodies that prevent the dissociation of p70 from p80 by high salt and detergent treatment was identified; monoclonal antibody (MAb) 162, a murine anti-Ku MAb, displays the same property. Autoantibodies that stabilize the p70-p80 interaction were found most frequently in sera containing both anti-p70 and anti-p80 antibodies. Autoantibodies to the native p80 subunit of Ku are more common than are anti-p70 antibodies. When anti-p70 antibodies were detected, they generally were found together with anti-p80. A novel type of autoantibody capable of stabilizing the p70/p80 heterodimer was identified in human sera for the first time. These "stabilizing" autoantibodies are found in sera containing both anti-p70 and anti-p80 antibodies, and also are produced by mice immunized with human Ku antigen. Autoimmunity to Ku may be initiated with an immune response to p80, followed by spreading to p70. We hypothesize that stabilizing antibodies could facilitate the spreading of autoimmunity from one subunit of Ku to another by altering the processing of p70 or p80 by antigen-presenting cells.
    Arthritis & Rheumatology 07/1997; 40(7):1344-53. DOI:10.1002/1529-0131(199707)40:7<1344::AID-ART20>3.0.CO;2-V · 7.87 Impact Factor
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    ABSTRACT: DNA-dependent protein kinase (DNA-PK) consists of a DNA binding subunit (Ku autoantigen), and a catalytic subunit (DNA-PKcs). In the present study, human autoantibodies that recognize novel antigenic determinants of DNA-PK were identified. One type of autoantibody stabilized the interaction of DNA-PKcs with Ku and recognized the DNA-PKcs -Ku complex, but not bio-chemically purified DNA-PKcs. Another type recognized purified DNA-PKcs. Autoantibodies to Ku (p70/p80 heterodimer), 'stabilizing' antibodies, and antibodies to DNA-PKcs comprise a linked autoantibody set, since antibodies recognizing purified DNA-PKcs were strongly associated with stabilizing antibodies, whereas stabilizing antibodies were strongly associated with anti-Ku. This hierarchical pattern of autoantibodies specific for components of DNA-PK (anti-Ku > stabilizing antibodies > anti-DNA-PKcs) may have implications for the pathogenesis of autoimmunity to DNA-PK and other chromatin particles. The data raise the possibility that altered antigen processing and/or stabilization of the DNA-PKcs-Ku complex due to autoantibody binding could play a role in spreading autoimmunity from Ku to the weakly associated antigen DNA-PKcs.
    Clinical & Experimental Immunology 09/1996; 105(3):460-7. DOI:10.1046/j.1365-2249.1996.d01-775.x · 3.28 Impact Factor
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    ABSTRACT: Antiglycyl tRNA synthetase is an unusual autoantibody specificity associated with polymyositis and dermatomyositis complicated by interstitial lung disease. We report here autoantibodies to glycyl tRNA synthetase in a patient with systemic lupus erythematosus and interstitial lung disease. During the course of her disease, the patient developed elevated muscle enzymes and worsening pulmonary function. A quantitative immunoprecipitation technique was developed to evaluate the relationship between autoantibody production and clinical manifestations in this patient. Increasing serum antiglycyl tRNA synthetase antibody levels correlated with the severity of the patient's interstitial lung disease and with the level of creatine phosphokinase.These results suggest that certain autoantibodies, such as antiglycyl tRNA synthetase, might reflect an underlying pathologic process (in this case, myositis and interstitial lung disease) irrespective of disease diagnosis, and that quantitative immunoprecipitation may be a useful technique for investigating the relationship between specific autoantibody production and organ involvement in systemic autoimmune disease, Quantitation of these autoantibodies may be useful clinically in monitoring disease activity and/or response to therapy.
    JCR Journal of Clinical Rheumatology 05/1996; 2(2):89-95. DOI:10.1097/00124743-199604000-00006 · 1.25 Impact Factor
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    ABSTRACT: We report a woman with systemic lupus erythematosus (SLE) with diffuse proliferative glomerulonephritis and anti-dsDNA antibodies whose serum contained autoantibodies specific for the phosphorylated form of RNA polymerase II (RNAP IIO), Su and ribosomal P antigen, as well as anti-topoisomerase I antibodies, a marker for scleroderma (SSc). Over 6 years, the patient exhibited clinical manifestations consistent with SLE without clinical evidence of scleroderma. The reactivity of her serum autoantibodies with the phosphoproteins ribosomal P, topoisomerase I, and RNAP IIO is consistent with recognition of autoepitopes comprised in part of phosphate groups. This may explain the unexpected coexistence of marker autoantibodies for SLE and scleroderma, possibly with implications for the mechanisms of autoantibody generation.
    Lupus 09/1995; 4(4):314-7. DOI:10.1177/096120339500400414 · 2.48 Impact Factor

Publication Stats

43 Citations
14.88 Total Impact Points

Institutions

  • 1995–1997
    • University of North Carolina at Chapel Hill
      • • Department of Medicine
      • • Department of Microbiology and Immunology
      North Carolina, United States
  • 1996
    • Keio University
      • School of Medicine
      Edo, Tōkyō, Japan