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73.874 715.25 Td
(erythematosus. Arthritis Rheum 1979;22:858-63.)Tj
-13.611 -10 Td
[(7.)-875 (Reichlin M, )-49.375 (W)]TJ
0.2 Tw 60.67 0 Td
(olfson-Reichlin M. Evidence for the participation of)Tj
0.408 Tw -46.96 -10 Td
(anti-ribosomal Pantibodies in lupus nephritis. Arthritis Rheum)Tj
0 Tw -0.038 -10 Td
(1999;42:2728-9.)Tj
-13.641 -10 Td
[(8.)-875 (Skinner RP, Maddison PJ. Analysis of polyethylene glycol )]TJ
0.2 Tw 13.565 -10 Td
(precipitates from SLE sera: antibody enrichment in association with)Tj
0 Tw 0.069 -10 Td
(disease activity. Clin Exp Rheumatol 1990;8:553-60.)Tj
-13.523 -10 Td
[(9.)-875 (Agnello )6.625 (V)]TJ
0.172 Tw 45.5 0 Td
(, Koffler D, Kunkel HG. Immune complex systems in the)Tj
0.2 Tw -31.985 -10 Td
(nephritis of systemic lupus erythematosus. Kidney Int 1973;3:90-9.)Tj
0 Tw -17.6 -10 Td
[(10.)-875 (Mannik M, )-50 (W)]TJ
0.2 Tw 62.201 0 Td
(ener MH. Deposition of antibodies to the )Tj
-44.541 -10 Td
(collagen-like region of C1q in renal glomeruli of patients with)Tj
0 Tw -0.169 -10 Td
(proliferative lupus glomerulonephritis. Arthritis Rheum)Tj
0.019 -10 Td
(1997;40:1504-11.)Tj
-17.141 -10 Td
[(1)31.25 (1.)-875 (Mannik M, Merrill CE, )-68.125 (W)62.625 (ener MH. Antibodies to human )]TJ
0.2 Tw 17.246 -10 Td
(myeloperoxidase in glomerular immune deposits of systemic lupus)Tj
0 Tw 0.056 -10 Td
(erythematosus. Lupus 2000;9:607-13.)Tj
-17.53 -10 Td
[(12.)-875 (W)]TJ
0.16901 Tw 23.801 0 Td
(ener MH, Mannik M. Selective losses of large immune)Tj
0.2 Tw -6.439 -10 Td
(complexes during density gradient ultracentrifugation and an)Tj
0.001 -10 Td
(approach for prevention of these losses. J Immunol Methods)Tj
0 Tw 0.116 -10 Td
(1985;84:1-10.)Tj
-17.641 -10 Td
(13.)Tj
0.2 Tw 17 0 Td
(Mannik M. Presence of covalent bonds between immune deposits)Tj
0.499 -10 Td
(and macromolecules in murine renal glomeruli. Clin Exp Immunol)Tj
0 Tw 0.049 -10 Td
(1996;103:285-8.)Tj
-17.391 -10 Td
[(14.)-875 (James JA, Kaufmann KM, Farris AD, )-88 (T)93.875 (aylor-Albert E, Lehman)]TJ
0.138 Tw 17.44 -10 Td
(TJA, Harley JB. An increased prevalence of Epstein-Barr virus)Tj
0.2 Tw 0.002 -10 Td
(infection in young patients suggests a possible etiology for)Tj
0.073 -10 Td
(systemic lupus erythematosus. J Clin Invest 1997;100:3019-26.)Tj
0 Tw -17.702 -10 Td
(15.)Tj
0.2 Tw 17 0 Td
(Kubes L. Experimental immune complex glomerulonephritis in the)Tj
0.713 -10 Td
[(mouse with two types of immune complexes. )33 (V)]TJ
0 Tw 153.517 0 Td
(irchows Arch B)Tj
-153.694 -10 Td
(Cell Pathol 1977;24:343-54.)Tj
-17.463 -10 Td
[(16.)-875 (Martensson U, Sj\232holm AG, Sturfelt G, )-87.375 (T)31.375 (ruedsson L, Laurell A-B.)]TJ
17.441 -10 Td
(W)Tj
0.2 Tw 6.801 0 Td
(estern blot analysis of human IgG reactive with the collagenous)Tj
-6.731 -10 Td
(portion of C1q: evidence of distinct binding specificities. Scand J)Tj
0 Tw 0.093 -10 Td
(Immunol 1992;144:3484-8.)Tj
-17.609 -10 Td
(17.)Tj
0.2 Tw 17 0 Td
(Costa O, Marion C, Monier JC, Roux B. Non-specific binding of)Tj
0.485 -10 Td
(heat-aggregated IgG to histone detected by ELISA. J Immunol)Tj
0 Tw -0.041 -10 Td
(Methods 1984;74:283-91.)Tj
246.559 360 Td
[(18.)-875 (Gussin HAE, )-50.5 (T)93.875 (selentis HN, )-49.875 (T)93.875 (eodorescu M. Noncognate binding to)]TJ
0.2 Tw 17.456 -10 Td
(histones of IgG from patients with idiopathic systemic lupus)Tj
0 Tw 0.159 -10 Td
(erythematosus. Clin Immunol 2000;96:150-61.)Tj
-17.466 -10 Td
[(19.)-875 (Stockl F, Muller S, Batsford S, et al. )-42.75 (A)-218.875 (role of histones and )]TJ
0.2 Tw 17.466 -10 Td
(ubiquitin in lupus nephritis? Clin Nephrol 1994;41:10-7.)Tj
0 Tw -17.698 -10 Td
(20.)Tj
0.2 Tw 17 0 Td
(McCoy RC. Nuclear localization of immunoglobulins in renal )Tj
0.117 Tw 0.729 -10 Td
(biopsies of patients with lupus nephritis. Am J Pathol 1972;)Tj
0 Tw -0.094 -10 Td
(68:469-78.)Tj
-17.613 -10 Td
(21.)Tj
0.172 Tw 17 0 Td
(Kerjaschki D, Miettinen A, Farquhar MG. Initial events in the)Tj
0.2 Tw 0.671 -10 Td
(formation of immune deposits in passive Heymann nephritis.)Tj
-0.076 -10 Td
(Gp330-anti-gp 330 immune complexes form in epithelial coated)Tj
0.095 -10 Td
(pits and rapidly become attached to the glomerular basement)Tj
0 Tw -0.052 -10 Td
(membrane. J Exp Med 1987;166:109-28.)Tj
-17.665 -10 Td
(22.)Tj
0.2 Tw 17 0 Td
[(Hylkema MN, van Bruggen MCJ, ten Hove )0.375 (T)]TJ
0 Tw 147.518 0 Td
(, et al. )Tj
0.16901 Tw -146.853 -10 Td
(Histone-containing immune complexes are to a large extent )Tj
0.41901 Tw -0.076 -10 Td
(responsible for anti-dsDNAreactivity in the Farr assay of active)Tj
0 Tw 0.092 -10 Td
(SLE patients. J Autoimmunity 2000;14:159-68.)Tj
-17.509 -10 Td
(23.)Tj
0.2 Tw 17 0 Td
(Jasin HE. Oxidative cross-linking of immune complexes by human)Tj
0.452 -10 Td
(polymorphonuclear leukocytes. J Clin Invest 1988;81:6-15.)Tj
0 Tw -17.586 -10 Td
(24.)Tj
0.2 Tw 17 0 Td
[(Furie RA, Cash JM, Cronin ME, et al. )0.5 (T)]TJ
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(reatment of systemic lupus)Tj
0.55 Tw -129.419 -10 Td
(erythematosus with LJP394. J Rheumatol 2001;28:257-65.)Tj
0 Tw -17.539 -10 Td
[(25.)-875 (McNeeley PA, Iverson GM, Furie RA, et al. Pre-treatment affinity)]TJ
0.492 Tw 17.605 -10 Td
(for LJP394 influences pharmacodynamic responses in lupus)Tj
0 Tw -0.148 -10 Td
(patients. Lupus 2001;10:526-32.)Tj
-17.358 -10 Td
[(26.)-875 (Spertini F, Leimgruber A, Morel B, et al. Idiotypic vaccination with)]TJ
0.388 Tw 17.481 -10 Td
(a murine anti-dsDNAantibody: phase I study in patients with)Tj
0.2 Tw -0.072 -10 Td
(nonactive systemic lupus erythematosus with nephritis. )Tj
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(J Rheumatol 1999;26:2602-8.)Tj
-17.522 -10 Td
[(27.)-875 (Kong D, Schuett )-43.625 (W)]TJ
0.2 Tw 79.702 0 Td
(, Dai J, et al. Development of cellulose-DNA)Tj
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(immunoadsorbent. Artif Organs 2002;26:200-8.)Tj
-17.365 -10 Td
(28.)Tj
0.2 Tw 17 0 Td
(Kong DL, Chen CZ, Lin EF)Tj
0 Tw 90.246 0 Td
[(,Yu)-343.875 (YT. Clinical trials of type I and in)]TJ
0.2 Tw -89.96 -10 Td
(vitro studies of type II immunoadsorbents for systemic lupus)Tj
0 Tw -0.009 -10 Td
[(erythematosus therapy)38.625 (.)-218.75 (Artif Organs 1998;22:644-50.)]TJ
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/TT0 10 Tf
0.91499 Tw 53.302 714 Td
(antibodies to nuclear antigens had penetrated the cells and)Tj
0.55 Tw 0.012 -12 Td
[(bound to nuclei. This is supported by the finding that post)2.5 (-)]TJ
0.21899 Tw -0.055 -12 Td
(mortem frozen and thawed kidney tissue from patients with)Tj
1.258 Tw 0.024 -12 Td
[(SLE showed IgG bound to cell nuclei by immunofluores)-22.8 (-)]TJ
2.48599 Tw 0.022 -12 Td
(cence microscopy)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 127.951 669.25 Tm
(20)Tj
/TT0 10 Tf
1 0 0 1 134.451 666 Tm
(.)Tj
2.48599 Tw 7.25 0 Td
(Therefore, we chose the method of)Tj
1.01601 Tw -88.434 -12 Td
(sonication of glomeruli until no intact nuclei were visible,)Tj
0.87601 Tw 0.015 -12 Td
[(followed by washing of GBM fragments. During the soni)-24.59 (-)]TJ
0.44901 Tw 0.034 -12 Td
(cation of isolated glomeruli some antibodies were removed)Tj
0 Tw 0.02 -12 Td
(from the immune deposits, as shown by increased IgG:HSA)Tj
0.56799 Tw 0.034 -12 Td
(molar ratio and by increased concentration of antibodies in)Tj
0.017 -12 Td
[(the sonication supernatant as compared to the serum surro)2.69 (-)]TJ
0 Tw 0.027 -12 Td
[(gate, )-524.5 (as )]TJ
0.2 Tc 42.485 0 Td
(described )Tj
0 Tc 47.065 0 Td
(for )Tj
0.188 Tc 19.16 0 Td
(anti-CLR)Tj
/TT0 6.25 Tf
0 Tc -1.438 Tw 1.04 0 0 1.04 201.398 585.25 Tm
(1 0)Tj
/TT0 10 Tf
0 Tw 1 0 0 1 208.022 582 Tm
(. )Tj
0.179 Tc 9.75 0 Td
(Immune )Tj
0.188 Tc 41.325 0 Td
(deposits)Tj
0 Tc 1.32401 Tw -205.722 -12 Td
(remained attached to the GBM fragments in experimental)Tj
0 Tw 0.017 -12 Td
(models )Tj
0.20799 Tc 37.387 0 Td
(after )Tj
0.188 Tc 27.065 0 Td
(sonication, )Tj
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(as )Tj
0.18201 Tc 16.08 0 Td
(determined )Tj
0 Tc 54.48 0 Td
(by )Tj
0.188 Tc 18 0 Td
(electron)Tj
0 Tc -206.298 -12 Td
(microscopy)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 100.117 549.25 Tm
(21)Tj
/TT0 10 Tf
1.82001 Tw 1 0 0 1 110.867 546 Tm
[(and by use of radiolabelled antibody mole)2.1 (-)]TJ
0 Tw -57.461 -12 Td
(cules)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 73.953 537.25 Tm
(13)Tj
/TT0 10 Tf
1 0 0 1 80.453 534 Tm
(.)Tj
3.289 Tw -15 -12.25 Td
(The possibility remains that antigen molecules from)Tj
3.07001 Tw -11.983 -12 Td
(immune deposits survived the extraction and re-formed)Tj
0 Tw 0.022 -12.25 Td
(immune complexes, thus limiting antibody detection. In this)Tj
1.86301 Tw -0.24 -12 Td
(report and in previous studies)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 179.014 488.75 Tm
[(10,1)28.08 (1)]TJ
/TT0 10 Tf
1.86301 Tw 1 0 0 1 193.327 485.5 Tm
(, the specific antibodies)Tj
1.98599 Tw -139.997 -12 Td
(and the recovered IgG sedimented largely as monomeric)Tj
1.243 Tw -0.052 -12.25 Td
(IgG on sucrose density gradient ultracentrifugation with a)Tj
3.08 Tw 0.027 -12 Td
(small heavier shoulder. In these experiments, described)Tj
0.55701 Tw 0.074 -12.25 Td
(methods were employed to prevent losses of large immune)Tj
-2.30901 Tw -0.05 -12 Td
(c o m p l e x e s)Tj
/TT0 6.25 Tf
-1.444 Tw 1.04 0 0 1.04 97.869 428.25 Tm
(1 2)Tj
/TT0 10 Tf
0 Tw 1 0 0 1 104.738 425 Tm
[(. )-375 (Thus, )-475 (these )]TJ
0.16701 Tc 66.047 0 Td
(findings )Tj
0.194 Tc 40.528 0 Td
(indicate )Tj
0 Tc 39.65 0 Td
[(that )-449.5 (lar)]TJ
-2.30901 Tw [0.3 (g e)]TJ
2.64799 Tw -197.579 -12 Td
(amounts of immune complexes were not present in the)Tj
2.054 Tw 0.017 -12.25 Td
(neutralized extracts of GBM fragments. Nonetheless, the)Tj
1.08099 Tw 0.029 -12 Td
(IgG that bound to histones was all larger than monomeric)Tj
-0.216 Tw -0.05 -12.25 Td
[(IgG. Also, DNAwas present in small quantities in the guani)1.6 (-)]TJ
0 Tw -0.04 -12 Td
[(dine )-399.7 (extracts )-474.4 (and )-399.8 (the )-399.7 (digestion )-474.5 (of )-375 (DNA)-625.5 (with )-424.8 (DNase)]TJ
2.162 Tw 0.116 -12 Td
[(increased the detection of antibodies to dsDNA)-397.9 (in some)]TJ
2.317 Tw -0.09 -12.25 Td
[(specimens. In extracts that contained no detectable anti)4.4 (-)]TJ
0 Tw 0.015 -12 Td
(bodies to dsDNA, however, the use of DNase did not reveal)Tj
0.39101 Tw -0.07 -12.25 Td
(previously undetected antibodies to dsDNA. Of note is that)Tj
0 Tw 0.024 -12 Td
(the DNase did not alter the binding of antibodies to SSAand)Tj
0.044 -12 Td
[(to Epstein-Barr VCA)-249.5 (antigens)]TJ
/TT0 6.25 Tf
1.04 0 0 1.04 174.19 295.25 Tm
(22)Tj
/TT0 10 Tf
1 0 0 1 180.69 292 Tm
(.)Tj
-115.25 -12 Td
(W)Tj
0.349 Tw 8.688 0 Td
(e were also concerned that the sonication of glomeruli)Tj
1.32899 Tw -20.873 -12 Td
[(may enhance binding of autoantibodies or IgG to compo)-22.3 (-)]TJ
1.213 Tw 0.015 -12 Td
[(nents of glomeruli. )1.1 (T)]TJ
1.14101 Tw 87.316 0 Td
(o test this possibility, an aliquot of a)Tj
2.05901 Tw -87.271 -12 Td
(non-SLE kidney was processed as usual, except prior to)Tj
1.396 Tw 0.027 -12 Td
(sonication 1.0 ml of diluted serum was added, containing)Tj
0.267 Tw 0.015 -12 Td
(20.7 \265g of antibodies to SSA. After overnight incubation at)Tj
-0.177 Tw 0.074 -12 Td
(4\241C, sonication and subsequent steps were performed by the)Tj
0 Tw 0.024 -12 Td
(usual protocol. In the guanidine extract 0.071% and 0.067%)Tj
0.14999 Tw 0.015 -12 Td
(of the added antibodies to SSAwere recovered in 2 separate)Tj
2.94 Tw -0.129 -12 Td
(experiments. These findings indicate that autoantibodies)Tj
0 Tw -0.057 -12 Td
(entrapped in glomeruli do not significantly contribute to the)Tj
0.25 Tw 0.012 -12 Td
(antibodies recovered from the GBM fragments.)Tj
0.248 Tw 12.191 -12 Td
(The recovery of IgG from GBM fragments by guanidine)Tj
0.964 Tw -12.221 -12 Td
(extraction was incomplete. Further extraction with SDS in)Tj
0.84399 Tw 0.027 -12 Td
(the presence of a reducing agent yielded small amounts of)Tj
0.84 Tw 0.017 -12 Td
(IgG heavy chains and light chains. In contrast, SDS in the)Tj
0 Tw 0.025 -12 Td
[(presence )-399.6 (of )-400 (iodoacetamide )-448.6 (released )-399.4 (no )-375 (detectable )-423.7 (IgG)]TJ
1.06799 Tw -0.055 -12 Td
(polypeptide chains. These findings indicate that some IgG)Tj
0.211 Tw 264.195 638 Td
[(molecules are linked to GBM macromolecules by intermol)3.8 (-)]TJ
2.86 Tw 0.019 -12 Td
(ecular disulfide bonds. The presence of covalent bonds)Tj
0 Tw -0.052 -12 Td
(between immune complexes and structural molecules of the)Tj
0.90401 Tw 0.017 -12 Td
(GBM has been described in a model of immune complex-)Tj
2.517 Tw 0.017 -12 Td
(induced lesions in mice)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 419.172 669.25 Tm
(13)Tj
/TT0 10 Tf
1 0 0 1 425.672 666 Tm
(.)Tj
2.517 Tw 7.25 0 Td
(The mechanism that leads to)Tj
1.125 Tw -115.524 -12 Td
(covalent attachment of components of immune complexes)Tj
0 Tw 0.01 -12 Td
(to molecules of the GBM may be related to the mediators of)Tj
0.02 -12 Td
(inflammation)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 371.055 633.25 Tm
(23)Tj
/TT0 10 Tf
1 0 0 1 377.555 630 Tm
(.)Tj
1.159 Tw -48.25 -12 Td
[(The finding that autoantibodies with multiple specifici)-21.1 (-)]TJ
0.284 Tw -11.985 -12 Td
(ties form the immune deposits in glomeruli of patients with)Tj
1.311 Tw 0.022 -12 Td
[(SLE has implications for developing therapeutic interven)3.7 (-)]TJ
2.556 Tw 0.019 -12 Td
[(tions for lupus glomerulonephritis. Suppressing or abro)1.2 (-)]TJ
0.155 Tw 0.034 -12 Td
(gating the antibody response to one antigen may not suffice)Tj
0.646 Tw -0.057 -12 Td
(to improve the course of lupus glomerulonephritis. Several)Tj
3.72099 Tw 0.025 -12 Td
(approaches have been developed and recommended to)Tj
1.689 Tw 0.007 -12 Td
[(specifically suppress antibodies to DNA. LJP)-398.9 (394, which)]TJ
0.16701 Tc 0 Tw -0.039 -12 Td
(consists )Tj
0 Tc 40.92 0 Td
[(of )-575 (4 )]TJ
0.188 Tc 29.33 0 Td
(double-stranded )Tj
0.19 Tc 75.174 0 Td
(oligodeoxynucleotides)Tj
0 Tc 1.019 Tw -145.463 -12 Td
(attached to an inert platform, was developed to act as a B)Tj
1.605 Tw 0.015 -12 Td
(cell toleragen)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 373.048 501.25 Tm
(24,25)Tj
/TT0 10 Tf
1.605 Tw 1 0 0 1 387.611 498 Tm
[(. Idiotypic vaccination with murine anti)-22.1 (-)]TJ
0 Tw -70.354 -12 Td
(bodies to dsDNA)Tj
0.446 Tw 72.835 0 Td
(was recommended to suppress antibodies)Tj
0 Tw -72.699 -12 Td
(to dsDNA)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 357.943 477.25 Tm
(26)Tj
/TT0 10 Tf
1 0 0 1 364.443 474 Tm
[(. Solid-phase DNAimmunoadsorbents for extra)-60.4 (-)]TJ
0.567 Tw -47.176 -12 Td
[(corporeal removal of antibodies to DNA)-273.6 (was suggested for)]TJ
1.229 Tw 0.016 -12 Td
(altering the course of lupus renal disease)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 487.375 453.25 Tm
(27,28)Tj
/TT0 10 Tf
1 0 0 1 502.187 450 Tm
(.)Tj
1.229 Tw 6 0 Td
[(These inter)0.8 (-)]TJ
-0.12801 Tw -190.739 -12 Td
(ventions or other approaches directed to antibodies with one)Tj
0 Tw 0.02 -12 Td
(defined specificity are unlikely to have a profound effect on)Tj
2.384 Tw -0.052 -12 Td
(the course of lupus glomerulonephritis. The presence of)Tj
0.55701 Tw -0.047 -12 Td
(discrete immune deposits with different autoantibodies and)Tj
0 Tw -0.05 -12 Td
(antigens, possibly cross-linked by C1q and antibodies to the)Tj
0.30901 Tw 0.02 -12 Td
(CLR of C1q, may not be altered much by the abrogation or)Tj
-0.33701 Tw 0.01 -12 Td
(suppression of antibodies to just one specific antigen present)Tj
0 Tw 0.027 -12 Td
(in the immune deposits.)Tj
/TT1 10 Tf
0.047 -24 Td
(ACKNOWLEDGMENT)Tj
/TT0 8 Tf
1.896 Tw 0.062 -10 Td
[(The authors thank Corinne L. Fligner, MD, Department of Pathology)64.625 (,)]TJ
0 Tw -0.141 -10 Td
[(University of )-76.5 (W)]TJ
0.30701 Tw 51.853 0 Td
(ashington, for her help in obtaining the kidney specimens,)Tj
2.071 Tw -51.802 -10 Td
[(and the Cooperative Human )32.375 (T)31.375 (issue Network, which is funded by the)]TJ
0.39999 Tw -0.058 -10 Td
[(National Cancer Institute, for providing some specimens. Other investiga\
)3.625 (-)]TJ
0.2 Tw 0.027 -10 Td
(tors may have received samples from these same tissues.)Tj
/TT1 10 Tf
0 Tw 0.1 -24 Td
(REFERENCES)Tj
/TT0 8 Tf
6.986 -10 Td
[(1.)-875 (Cavallo )6.875 (T)]TJ
0.164 Tw 44.22 0 Td
(, Cameron WR, Lapenas D. Immunopathology of early)Tj
0 Tw -30.701 -10 Td
[(and clinically silent lupus nephropathy)-35.125 (.)-218.75 (Am J Pathol 1977;87:1-18.)]TJ
-13.709 -10 Td
(2.)Tj
0.2 Tw 13 0 Td
(Appel GB, Silva FG, Pirani CL, Meltzer JI, Estes D. Renal )Tj
0.595 -10 Td
(involvement in systemic lupus erythematosus: a study of 56)Tj
0 Tw 0.131 -10 Td
(patients emphasizing histologic classification. Medicine)Tj
-0.161 -10 Td
(1978;57:371-410.)Tj
-13.391 -10 Td
(3.)Tj
0.164 Tw 13 0 Td
(Koffler D, Schur PH, Kunkel HG. Immunological studies)Tj
0.2 Tw 0.568 -10 Td
(concerning the nephritis of systemic lupus erythematosus. J Exp)Tj
0 Tw -0.134 -10 Td
(Med 1967;126:607-24.)Tj
-13.527 -10 Td
[(4.)-875 (Koffler D, Agnello )19 (V,)]TJ
0.2 Tw 84.721 0 Td
(Thoburn R, Kunkel HG. Systemic lupus)Tj
-71.09 -10 Td
(erythematosus: prototype of immune complex nephritis in man. )Tj
0 Tw -0.134 -10 Td
(J Exp Med 1971;134:169s-79s.)Tj
-13.4 -10 Td
(5.)Tj
0.2 Tw 13 0 Td
(Krishnan C, Kaplan MH. Immunopathologic studies of systemic)Tj
0.164 Tw 0.318 -10 Td
(lupus erythematosus II. Antinuclear reaction of gamma globulin)Tj
0.2 Tw 0.177 -10 Td
(eluted from homogenates and isolated glomeruli of kidneys from)Tj
0.049 -10 Td
(patients with lupus nephritis. J Clin Invest 1967;46:569-79.)Tj
0 Tw -13.608 -10 Td
(6.)Tj
0.2 Tw 13 0 Td
(Maddison PJ, Reichlin M. Deposition of antibodies to a soluble)Tj
0.62 -10 Td
(cytoplasmic antigen in the kidneys of patients with systemic lupus)Tj
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(Mannik, et al: Autoantibodies in lupus glomeruli)Tj
487.407 -0.25 Td
(1503)Tj
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/TT0 10 Tf
53.263 713 Td
(antigen)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 82.946 716.25 Tm
(15)Tj
/TT0 10 Tf
2.106 Tw 1 0 0 1 89.446 713 Tm
(. It is likely that the same holds true in human)Tj
0 Tw -36.171 -12 Td
(diseases, provided that the different antigenic molecules are)Tj
1.582 Tw 0.2 -12 Td
[(not cross-reactive. )25.8 (W)75.2 (e have previously suggested that the)]TJ
-0.16499 Tw -0.001 -12 Td
(antibodies to CLR of C1q bind to C1q deposited on immune)Tj
0.175 Tc 0 Tw 0.007 -12 Td
(complexes )Tj
0.179 Tc 54.514 0 Td
(formed )Tj
0 Tc 40.127 0 Td
(with )Tj
0.14999 Tc 28.528 0 Td
(different )Tj
0.188 Tc 45.924 0 Td
(antigen-antibody)Tj
0 Tc -169.241 -12 Td
(systems)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 85.003 656.25 Tm
(10)Tj
/TT0 10 Tf
-0.20399 Tw 1 0 0 1 91.503 653 Tm
(. Our observations that enrichment of antibodies to)Tj
1.714 Tw -38.143 -12 Td
(CLR of C1q was associated with multiple autoantibodies)Tj
1.162 Tw 0.017 -12 Td
(and with proliferative forms of glomerulonephritis tend to)Tj
0.22 Tw 0.027 -12 Td
(support the hypothesis that antibodies to CLR of C1q could)Tj
2.46201 Tw 0.015 -12 Td
(facilitate formation of larger immune deposits, and thus)Tj
0.84801 Tw -0.05 -12 Td
(promote activation of complement and other inflammatory)Tj
3.347 Tw 0.012 -12 Td
(mechanisms. Formation of immune complexes between)Tj
1.59399 Tw 0.017 -12 Td
(anti-CLR and fluid-phase C1q, followed by deposition in)Tj
0.461 Tw 0.017 -12 Td
(glomeruli, is unlikely because these antibodies do not react)Tj
1.258 Tw 0.015 -12 Td
(with free fluid-phase C1q)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 159.676 548.25 Tm
(16)Tj
/TT0 10 Tf
1 0 0 1 166.176 545 Tm
(.)Tj
0.883 Tw 5.75 0 Td
(Alternatively, C1q potentially)Tj
0.35899 Tw -118.536 -12 Td
[(could interact with DNA)-224 (or other macromolecules and then)]TJ
-0.16499 Tw -0.038 -12 Td
(bind anti-CLR. Regardless of the mechanisms leading to the)Tj
0.117 Tw 0.017 -12 Td
(enrichment of antibodies to the CLR of C1q in glomeruli of)Tj
1.75999 Tw 0.015 -12 Td
[(patients with proliferative lupus renal disease, these anti)3.3 (-)]TJ
0.707 Tw 0.027 -12 Td
(bodies are likely to enhance the inflammatory processes in)Tj
0 Tw 0.02 -12 Td
(glomeruli.)Tj
2.867 Tw 11.882 -12 Td
(Antibodies to dsDNA, probably the most thoroughly)Tj
0.567 Tw -11.978 -12 Td
(studied of any antibodies, were enriched in 6 extracts from)Tj
2.313 Tw 0.024 -12 Td
(the GBM fragments. DNase I digestion of 3 of these 6)Tj
1.959 Tw 0.032 -12 Td
(extracts increased the amount of detectable antibodies to)Tj
1.321 Tw 0.015 -12 Td
(dsDNA, yielding a higher enrichment of these antibodies.)Tj
0.383 Tw 0.022 -12 Td
(This finding suggested the presence of DNAin the extracts,)Tj
0 Tw -0.054 -12 Td
[(possibly )-400 (as )-375 (a )-399.8 (result )-374.7 (of )-375 (the )-399.7 (sonication )-374.4 (and )-374.8 (incomplete)]TJ
0.867 Tw 0.093 -12 Td
(removal of DNA. The presence of small amounts of DNA)Tj
0.146 Tw -0.037 -12 Td
[(was confirmed by use of PicoGreen in a fluorometric assay)77 (.)]TJ
-0.36301 Tw 11.934 -12 Td
(The enrichment of antibodies to Sm, SSA, and SSB in the)Tj
2.03999 Tw -11.978 -12.25 Td
(extracts exceeded the frequency of antibodies to dsDNA)Tj
1.26401 Tw 0.024 -12 Td
(enriched in the extracts. This is the first demonstration of)Tj
3.22301 Tw -0.045 -12.25 Td
(enrichment of antibodies to Sm in glomerular immune)Tj
-0.3 Tw 0.015 -12 Td
[(deposits of patients with SLE, and a confirmation and exten)2.8 (-)]TJ
0.842 Tw 0.022 -12 Td
(sion of previous reports of the enrichment of antibodies to)Tj
0.314 Tw 0.027 -12.25 Td
[(SSAand SSB in these deposits. )0.1 (W)]TJ
0 Tw 136.687 0 Td
(e found the enrichment of)Tj
3.17101 Tw -136.849 -12 Td
[(antibodies to SSA)-524.6 (in 15 of the studied 23 extracts of)]TJ
0 Tw 0.15 -12.25 Td
(glomeruli, and enrichment of antibodies to SSB in 10 of the)Tj
0.017 -12 Td
(23 extracts.)Tj
1.07899 Tw 11.844 -12 Td
(The detection and presence of antibodies to histones in)Tj
2.31599 Tw -11.985 -12 Td
(extracts of GBM remain ambiguous for several reasons.)Tj
1.55 Tw 0.034 -12 Td
(First, the titration curves for IgG binding to histones had)Tj
3.19 Tw 0.029 -12 Td
(aberrant patterns, and DNase I digestion converted the)Tj
1.12199 Tw 0.025 -12 Td
(patterns to those expected for serial dilutions. Second, the)Tj
-0.144 Tw 0.022 -12 Td
(addition of calf thymus DNAblocked the binding of extracts)Tj
0.17599 Tw -0.097 -12 Td
(and of aggregated IgG to histones. These findings indicated)Tj
0 Tw -0.05 -12 Td
(that binding of DNA)Tj
0.284 Tw 86.149 0 Td
(to histones interfered with the binding)Tj
0 Tw -86.109 -12 Td
[(of IgG to histones. Third, the sucrose density gradient ultra)-52 (-)]TJ
0.60699 Tw -0.04 -12 Td
(centrifugation experiments showed that the IgG that bound)Tj
0 Tw 0.02 -12 Td
(to )Tj
0.16701 Tc 15.278 0 Td
(histones )Tj
0 Tc 41.278 0 Td
[(was )-500.2 (of )-500 (high )]TJ
0.175 Tc 64.41 0 Td
(molecular )Tj
0.179 Tc 48.73 0 Td
(weight )Tj
0 Tc 35.217 0 Td
[(and )-499.8 (not)]TJ
0.21001 Tw -204.784 -12 Td
(monomeric IgG. Fourth, previous reports had indicated that)Tj
0.84399 Tw 0.024 -12 Td
(aggregated IgG binds to histones in a non-immunospecific)Tj
0 Tw 0.022 -12 Td
(manner)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 83.436 79.25 Tm
(17,18)Tj
/TT0 10 Tf
0.32401 Tw 1 0 0 1 100.999 76 Tm
(and that in sera from patients with SLE the IgG)Tj
0.188 Tc 0 Tw 216.34 638 Td
(binding )Tj
0 Tc 40.807 0 Td
(to )Tj
0.16701 Tc 17.278 0 Td
[(histones )-649.49 (represented )]TJ
0.2 Tc 100.112 0 Td
(primarily )Tj
0 Tc 48.212 0 Td
(immune)Tj
-206.477 -12 Td
(complexes)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 360.035 705.25 Tm
(17)Tj
/TT0 10 Tf
0.51401 Tw 1 0 0 1 366.535 702 Tm
(. Our experiments with heated serum or heated)Tj
2.552 Tw -49.242 -12 Td
(purified human IgG concur with these previous reports.)Tj
0 Tw 0.029 -12 Td
(Therefore, we have used the term \322IgG binding to histones\323)Tj
0.74001 Tw 0.024 -12 Td
(and not antibodies to histones. The presence of histones in)Tj
-0.14799 Tw -0.052 -12 Td
[(glomeruli of patients with SLE has been shown by immuno)-22.4 (-)]TJ
1.19701 Tw 0.022 -12 Td
(fluorescence microscopy using antibodies to histone H3)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 548.339 645.25 Tm
(19)Tj
/TT0 10 Tf
1 0 0 1 554.839 642 Tm
(.)Tj
0.765 Tw -237.5 -12 Td
(Whether these histone molecules have bound antibodies to)Tj
0.369 Tw 0.012 -12 Td
(histones or attracted circulating immune complexes has not)Tj
-0.233 Tw 0.017 -12 Td
(been clarified. The latter, however, raises the possibility that)Tj
-0.32001 Tw -0.001 -12 Td
(immune complexes in circulation, containing autoantibodies)Tj
2.60699 Tw 0.007 -12 Td
(or containing unrelated exogenous antigens and specific)Tj
0.883 Tw 0.015 -12 Td
(antibodies, may become deposited in glomeruli of patients)Tj
0.25 Tw 0.012 -12 Td
(with SLE by binding to histones in glomeruli.)Tj
2.67599 Tw 12.08 -12 Td
(Antibodies to a number of other antigens have been)Tj
0.85899 Tw -11.985 -12 Td
[(reported in the sera of patients with SLE. )51.8 (W)50.2 (e searched for)]TJ
-0.27299 Tw -0.245 -12 Td
[(antibodies to human MPO in all specimens and did not iden)-22.7 (-)]TJ
1.64301 Tw 0.017 -12 Td
(tify additional presence of these antibodies, other than in)Tj
1.134 Tw 0.017 -12 Td
(K15 as reported)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 383.672 501.25 Tm
(11)Tj
/TT0 10 Tf
1 0 0 1 389.672 498 Tm
[(.)-350 (W)]TJ
1.134 Tw 14.438 0 Td
[(e did not detect the presence of anti)-22.8 (-)]TJ
0 Tw -86.844 -12 Td
(bodies to cathepsin G, lactoferrin, or \247)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 471.037 482.5 Tm
(2)Tj
/TT0 10 Tf
1 0 0 1 474.412 486 Tm
[(-GPI. As noted, anti)53.7 (-)]TJ
0.276 Tw -156.937 -12 Td
(bodies to tetanus toxoid, to Epstein-Barr virus VCA, and to)Tj
1.298 Tw -0.047 -12 Td
(EBNA-1 were detected in the serum surrogates, but these)Tj
0 Tw 0.029 -12 Td
(antibodies were not enriched in extracts of GBM fragments.)Tj
0.291 Tw 0.029 -12 Td
(These findings indicate that Epstein-Barr viral antigens and)Tj
0.35899 Tw -0.228 -12 Td
(specific antibodies to these viral antigens do not participate)Tj
0 Tw 0.017 -12 Td
[(in the formation of immune complexes in glomeruli. )58.7 (W)100.2 (e did)]TJ
0.425 Tw -0.011 -12 Td
(not study rheumatoid factors or antibodies to the ribosomal)Tj
0.022 -12 Td
(P)Tj
0.25 Tw 8.062 0 Td
(proteins in the guanidine extracts.)Tj
0.73199 Tw 3.989 -12 Td
(Our studies allowed the calculation of the proportion of)Tj
1.265 Tw -11.978 -12 Td
(total recovered IgG that was represented by the identified)Tj
0.528 Tw 0.024 -12 Td
[(antibodies. As seen in )25.8 (T)]TJ
0.653 Tw 97.482 0 Td
(able 2, most of the percentages are)Tj
0.498 Tw -97.535 -12 Td
(small, below 1.0%, and infrequently are between 1.0% and)Tj
3.263 Tw 0.02 -12 Td
(10%. The percentages for IgG binding to histones are)Tj
1.52499 Tw -0.047 -12 Td
[(higher, and as discussed above may represent IgG aggre)1.29 (-)]TJ
0 Tw 0.177 -12 Td
(gates or immune complexes.)Tj
0.755 Tw 11.914 -12.25 Td
(The presence of the bulk of IgG in the extracts remains)Tj
0 Tw -11.976 -12 Td
(unexplained, but several possibilities need to be considered.)Tj
-0.248 Tw 0.017 -12.25 Td
[(First, the loss of antibody activity by exposure to 6 M guani)1.8 (-)]TJ
3.062 Tw 0.024 -12 Td
(dine was ruled out by the demonstration that antibody)Tj
1.272 Tw 0.012 -12 Td
(activity was not lost by exposure to this potent molecular)Tj
0 Tw 0.017 -12.25 Td
(perturbant)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 358.333 236.5 Tm
(11)Tj
/TT0 10 Tf
1.12 Tw 1 0 0 1 364.583 233.25 Tm
(. Second, the recovery of known amounts of a)Tj
-0.20599 Tw -47.203 -12 Td
(specific antibody was evaluated and found to be complete in)Tj
1.888 Tw 0.012 -12.25 Td
(an equivalent system)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 405.035 212.5 Tm
(11)Tj
/TT0 10 Tf
1 0 0 1 411.035 209 Tm
(.)Tj
1.888 Tw 6.75 0 Td
(Third, antibodies to yet-unknown)Tj
0.911 Tw -100.469 -12 Td
(antigens may be present. Fourth, small amounts of normal)Tj
1.83099 Tw 0.022 -12 Td
(IgG and other serum proteins may be associated with or)Tj
0.507 Tw 0.027 -12.25 Td
(entrapped in the GBM and not removed by washing with a)Tj
0 Tw 0.017 -12 Td
[(neutral buffer)58.3 (.)-225 (This possibility is supported in part by recov)79.4 (-)]TJ
2.51199 Tw 0.013 -12.25 Td
(ering IgG from glomeruli isolated from non-lupus renal)Tj
0.771 Tw 0.029 -12 Td
(tissues and by detecting in some specimens small amounts)Tj
1.27901 Tw 0.02 -12 Td
(of antibodies to tetanus toxoid, antibodies to Epstein-Barr)Tj
2.741 Tw 0.02 -12.25 Td
(virus VCA, and EBNA-1 in the GBM extracts without)Tj
2.58099 Tw -0.042 -12 Td
(evidence of being enriched in comparison to the serum)Tj
0 Tw 0.015 -12.25 Td
(surrogate.)Tj
-0.315 Tw 11.957 -12 Td
(The possibility exists that in the postmortem tissues some)Tj
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(The Journal of Rheumatology 2003; 30:7)Tj
0 Tw -370.352 -0.25 Td
(1502)Tj
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BT
/TT0 10 Tf
0.248 Tw 53.317 714 Td
(exceeded 1.0% of total IgG in 8 specimens. The percentage)Tj
1.44501 Tw -0.055 -12 Td
(of IgG bound to histones, however, exceeded 1.0% in all)Tj
0.77499 Tw 0.167 -12 Td
(specimens that required DNase I digestion to quantify IgG)Tj
0.509 Tw 0.029 -12 Td
(binding to histones. As noted in the preceding section, IgG)Tj
0.286 Tw -0.181 -12 Td
(binding to histones may not represent specific antibodies to)Tj
0 Tw 0.02 -12 Td
(histones. Less than 10% of the total IgG is accounted for by)Tj
0.72099 Tw 0.027 -12 Td
(identified antibodies, with 2 exceptions: antibodies to SSA)Tj
0.16701 Tw 0.019 -12 Td
(in K3 \(11.1%\) and antibodies to MPO in K15 \(11.9%\))Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 272.32 633.25 Tm
(11)Tj
/TT0 10 Tf
1 0 0 1 278.32 630 Tm
(.)Tj
/TT1 10 Tf
1.024 Tw -225 -14.5 Td
(Detection of other antibodies.)Tj
/TT0 10 Tf
125.745 0 Td
[(W)75.2 (e previously reported that)]TJ
1.05099 Tw -125.775 -11.75 Td
(in K15 antibodies to human MPO were concentrated 103-)Tj
0.474 Tw 0.022 -12 Td
(fold in the guanidine extract and that these antibodies were)Tj
0.903 Tw 0.015 -11.75 Td
(not detected in the remaining 18 specimens studied at that)Tj
0 Tw 0.01 -12 Td
(time)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 71.11 571.25 Tm
(11)Tj
/TT0 10 Tf
1.14999 Tw 1 0 0 1 77.36 568 Tm
(. In the same report, antibodies to cathepsin G were)Tj
1.748 Tw -23.883 -12 Td
[(not detected in the serum surrogates or sonication super)2.7 (-)]TJ
0.44299 Tw -0.223 -11.75 Td
(natants in any of 19 specimens. Antibodies to human MPO)Tj
1.12 Tw 0.071 -12 Td
(and to cathepsin G were searched for in K22 to K25, and)Tj
-0.22501 Tw 0.025 -11.75 Td
(were not detected. Antibodies to tetanus toxoid were present)Tj
2.972 Tw 0.071 -12 Td
(in serum surrogates of all 23 specimens, but were not)Tj
0.69 Tw 0.027 -12 Td
(concentrated in the extracts of GBM fragments. Since 5 of)Tj
0 Tw 0.027 -11.75 Td
[(the )-399.7 (23 )-375 (kidney )-424.7 (specimens )-424.5 (studied )-449.7 (were )-374.9 (obtained )-424.4 (from)]TJ
0.8 Tw -0.223 -12 Td
(patients who died with the antiphospholipid syndrome, the)Tj
0.427 Tw 0.015 -11.75 Td
(presence of antibodies to \247)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 162.412 457.5 Tm
(2)Tj
/TT0 10 Tf
0.36501 Tw 1 0 0 1 165.537 461 Tm
(-GPI was examined. The serum)Tj
0.216 Tw -112.189 -12 Td
[(surrogates and sonication supernatants were tested for pres)2.3 (-)]TJ
1.343 Tw 0.039 -12 Td
(ence of these antibodies in all 23 specimens and all were)Tj
0.601 Tw 0.017 -11.75 Td
[(negative \(data not shown\). )51.3 (A)-250.2 (high prevalence of antibodies)]TJ
0 Tw 0.017 -12 Td
(to Epstein-Barr VCAand EBNA-1 has been reported in sera)Tj
-0.115 -11.75 Td
(of patients with SLE)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 134.934 404.75 Tm
(14)Tj
/TT0 10 Tf
1 0 0 1 141.434 401.5 Tm
(.)Tj
-0.28799 Tw 4.75 0 Td
[(Therefore, the presence of these anti)2.1 (-)]TJ
0.425 Tw -92.881 -12 Td
(bodies was tested in all specimens. Antibodies to VCA)Tj
0 Tw 225.594 0 Td
(and)Tj
1.718 Tw -225.562 -12 Td
(to EBNA-1 were found in 23 of 23 and 22 of 23 serum)Tj
0.188 Tc 0 Tw 0.024 -11.75 Td
(surrogates, )Tj
0.125 Tc 53.349 0 Td
(respectively. )Tj
0 Tc 60.061 0 Td
(The )Tj
0.18201 Tc 23.797 0 Td
(sonication )Tj
0.16701 Tc 50.604 0 Td
(supernatants)Tj
0 Tc 1.717 Tw -187.765 -12 Td
(contained lesser amounts of these antibodies without any)Tj
2.33701 Tw 0.02 -11.75 Td
(evidence for enrichment. In 6 specimens, K1, K3, K12,)Tj
0 Tw 0.022 -12 Td
[(K15, K24, and K25, the guanidine extract of the GBM frag)20.6 (-)]TJ
0.53 Tw 0.024 -12 Td
(ments was examined for antibodies to VCA)Tj
0.61301 Tw 180.896 0 Td
(and to EBNA-)Tj
1.509 Tw -181.005 -11.75 Td
(1. Low levels of these antibodies were detected in 4, but)Tj
0.25 Tw 0.017 -12 Td
(were not enriched in the guanidine extracts.)Tj
/TT1 10 Tf
-0.02499 Tc 0 Tw -0.097 -14.25 Td
(Studies to determine if extraction of IgG with 6 M guanidine)Tj
0 Tc 0.131 -12 Td
(was complete. )Tj
/TT0 10 Tf
59.155 0 Td
(Studies in mice indicated that extraction with)Tj
-0.08099 Tc -59.186 -12 Td
(6 M guanidine or with SDS did not release all IgG molecules)Tj
-0.101 Tc -0.072 -12 Td
(present in immune deposits in GBM fragments and that some)Tj
0.04401 Tc 0.046 -12 Td
(of these molecules were covalently attached to components)Tj
0 Tc -0.088 -12 Td
[(of )-275 (the )-274.7 (GBM)]TJ
/TT0 6.25 Tf
-1.59399 Tw 1.04 0 0 1.04 106.849 223.25 Tm
(1 3)Tj
/TT0 10 Tf
0 Tw 1 0 0 1 113.317 220 Tm
[(. )-275 (For )-275.2 (this )-249.8 (reason, )-249.9 (further )-249.7 (extractions )-224.2 (were)]TJ
0.071 Tc -60.053 -12 Td
(performed on the centrifugation pellet after extraction with)Tj
-0.063 Tc -0.013 -12 Td
(guanidine, as described in Materials and Methods. The pellet)Tj
-0.11 Tc 0.068 -12 Td
(from 6 specimens \(K14, K16, K19, K21, K23, and K24\) after)Tj
0.116 Tc 0.088 -12 Td
(guanidine extraction was divided into 2 equal aliquots and)Tj
0.259 Tc 0.026 -12 Td
(extracted with 2% SDS, one half also containing 0.03 M)Tj
0.02499 Tc 0.041 -12 Td
(dithiothreitol and the other half containing 0.001 M iodoac-)Tj
0 Tc -0.195 -12 Td
[(etamide. )-224 (The )-249.7 (supernatants )-199.5 (were )-249.9 (analyzed )-224.2 (by )-250 (SDS-P)]TJ
-2.55 Tw 219.629 0 Td
(A G E)Tj
0 Tw -219.548 -12 Td
[(under )-274.9 (reducing )-249.5 (conditions )-224.5 (and )]TJ
-0.188 Tc 134.357 0 Td
(Western )Tj
0 Tc 37.315 0 Td
[(blotting. )-199.3 (All )-299.8 (the)]TJ
0.19299 Tc -171.642 -12 Td
(examined specimens showed release of IgG heavy chains)Tj
0 Tc -0.111 -12 Td
[(\(Figure )-199.8 (4\) )]TJ
0.14999 Tc 46.518 0 Td
(and light )Tj
0.20799 Tc 41.523 0 Td
(chains \(data not shown\) )Tj
0 Tc 105.004 0 Td
(in )Tj
0.25 Tc 12.278 0 Td
(the SDS)Tj
0.09801 Tc -205.188 -12 Td
(extract in the presence of dithiothreitol, but not in the SDS)Tj
0 Tc -0.134 -12 Td
[(extract in the presence of iodoac)27.2 (etamide.)]TJ
/TT2 10 Tf
264.058 323 Td
(DISCUSSION)Tj
/TT0 10 Tf
1.813 Tw 0.133 -12 Td
(The notable finding in our study was that autoantibodies)Tj
2.188 Tw 0.015 -12 Td
(with multiple different specificities were enriched in the)Tj
0.562 Tw -0.047 -12 Td
(glomerular immune deposits in patients with SLE who had)Tj
3.004 Tw 0.02 -12 Td
(died. At the inception of the present investigations we)Tj
1.634 Tw -0.184 -12 Td
(sought to include postmortem kidneys from patients with)Tj
0.284 Tw 0.02 -12 Td
(SLE regardless of the cause of death. Therefore, among the)Tj
3.22501 Tw -0.045 -12 Td
(23 studied specimens a spectrum of renal involvement)Tj
1.71201 Tw 0.017 -12 Td
[(existed at the time of death. Proliferative lupus glomeru)-21.6 (-)]TJ
0 Tw 0.022 -12 Td
[(lonephritis, i.e., WHO class III or IV)-268.2 (lesions, was present in)]TJ
0.077 -12 Td
(14 specimens. Three of these specimens came from patients)Tj
0.56799 Tw -0.047 -12 Td
(with endstage renal disease on dialysis for variable periods)Tj
0.759 Tw 0.029 -12 Td
(of time. In the guanidine extract of GBM fragments of K9)Tj
0.382 Tw 0.027 -12 Td
(no specific antibodies were enriched, and in K10 extracts 2)Tj
0 Tw 0.022 -12 Td
(specific antibodies were enriched. In 3 specimens with class)Tj
0.029 -12 Td
[(III lesions antibodies with one or 2 specificities were recov)-36.7 (-)]TJ
1.537 Tw 0.037 -12 Td
(ered from the GBM fragments. In 8 of the 14 specimens)Tj
0.76601 Tw 0.029 -12 Td
[(with proliferative lupus glomerulonephritis 3 or more anti)3.5 (-)]TJ
2.02699 Tw -0.223 -12 Td
(body specificities were enriched in the extracts of GBM)Tj
0 Tw 0.027 -12 Td
(fragments. Although the presence of these autoantibodies in)Tj
0.339 Tw 0.071 -12 Td
(the GBM of kidneys from SLE patients does not prove that)Tj
1.317 Tw 0.024 -12 Td
(they are pathogenic, the fact that they are enriched in the)Tj
0 Tw 0.01 -12 Td
[(kidneys )-449.8 (of )]TJ
0.13901 Tc 53.188 0 Td
(patients )Tj
0 Tc 38.604 0 Td
(with )Tj
0.125 Tc 24.528 0 Td
(proliferative )Tj
0 Tc 57.419 0 Td
(lupus )Tj
0.15601 Tc 28.42 0 Td
(glomeru-)Tj
0 Tc 1.606 Tw -202.095 -12 Td
(lonephritis supports a role for these autoantibodies in the)Tj
0 Tw 0.024 -12 Td
(pathogenesis of lupus glomerulonephritis.)Tj
1.42599 Tw 12.004 -12 Td
(Studies in mice have shown that in experimental renal)Tj
1.2 Tw -12.235 -12 Td
(diseases induced simultaneously with 2 different antigens,)Tj
1.15601 Tw 0.203 -12 Td
(individual immune deposits in glomeruli contain only one)Tj
ET
1 g
407.25 745.75 150 15.25 re
f
q
30 31 552 730 re
W n
BT
0 g
/TT1 8 Tf
0 Tw 53.957 36.75 Td
(Mannik, et al: Autoantibodies in lupus glomeruli)Tj
487.407 -0.25 Td
(1501)Tj
ET
54.25 54.25 504 1 re
f
Q
q
229.5 0 0 145 322.25 577.75 cm
/Im0 Do
Q
q
318.25 554.75 239 24 re
W n
q
0 g
241 0 0 24 316.25 554.75 cm
/Im1 Do
Q
Q
BT
0 g
/TT1 8 Tf
0 Tw 318.364 545.25 Td
(Figure 4.)Tj
/TT0 8 Tf
0.936 Tw 33.209 0 Td
(Immunoblot developed with antibodies to the Fc fragments of)Tj
0.323 Tw -33.082 -10 Td
(human IgG. SDS-PAGE was run under reducing conditions using 0.01 M)Tj
0.466 Tw -0.232 -10 Td
(dithiothreitol. Lane 1 contains molecular weight markers, the fourth ban\
d)Tj
0.923 Tw 0.018 -10 Td
(from the top having size 47 kDa. Lane 2 is K19 sonication supernatant,)Tj
0.414 Tw 0.018 -10 Td
(containing 9 ng of IgG. Lane 3 is 25 \265l of SDS and 0.03 M dithiothrei\
tol)Tj
0.627 Tw 0.021 -10 Td
[(extract of half of the K19 pellet of glomerular basement membrane frag)4 (-)]TJ
0 Tw 0.025 -10 Td
(ments after extraction with guanidine. Lane 4 is 25 \265l of SDS and 0.0\
01 M)Tj
0.136 Tw 0.023 -10 Td
(iodoacetamide extract of the other half of the same K19 pellet. Lanes 5,\
6,)Tj
1.077 Tw 0.016 -10 Td
(7, and 8 are human IgG in increasing amounts per lane \(5, 20, 50, 100)Tj
0.463 Tw 0.016 -10 Td
(ng/lane\). IgG heavy chains are present in the SDS extract in the presen\
ce)Tj
-0.254 Tw 0.025 -10 Td
[(of a reducing agent and absent in the SDS extract in the presence of iod\
oac)35.125 (-)]TJ
0 Tw 0.021 -10 Td
(etamide.)Tj
ET
1 g
108.25 48.75 397 11.25 re
f
108.75 49.25 396 10.25 re
f
q
0 g
397 0 0 11.25 108.25 48.75 cm
/Im2 Do
Q
q
0 0 612 792 re
W n
BT
0 0 0 rg
/T1_0 8 Tf
117.48 51 Td
(Personal, non-commercial use only. The Journal of Rheumatology Copyrig\
ht \251 2003. All rights reserved.)Tj
ET
Q
BT
0 g
/T1_1 1 Tf
10 0 0 10 540 17 Tm
( )Tj
0 0.48627 0.77255 rg
-7.22298 0 Td
(www.jrheum.org)Tj
0 g
-16.72996 0 Td
(Downloaded on March 29, 2024 from )Tj
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