Abstract
Rabbit antiserum raised against a normal-derived monoclonal anti-DNA antibody KIM 4.6.3 (IgM lambda) was used for idiotype analyses. This anti-serum (anti-4.6.3 ID) was rendered specific for KIM 4.6.3 idiotype (4.6.3 ID) by absorption with normal human IgM and IgG. The specificity of anti-4.6.3 was shown by its ability to bind to KIM 4.6.3 antibody but not to normal human IgM and IgG, by inhibition of anti-4.6.3 ID reactivity with KIM 4.6.3 antibody by the homologous monoclonal antibody and by the ability of anti-4.6.3 ID to inhibit the binding of single stranded DNA with KIM 4.6.3 antibody. The 4.6.3 ID was found to be commonly expressed since it was detected among 33% (10/30) DNA and 32% (23/72) non-DNA-reactive monoclonal antibodies that were obtained from five different unrelated normal individuals. The binding to ssDNA of the majority of idiotype positive anti-DNA antibodies however was not blocked by anti-4.6.3 ID suggesting that among these other monoclonal antibodies its expression is outside of the antigen binding site. The 4.6.3 ID, which was present among some normal-derived monoclonal IgM molecules was also found at a high frequency (90%) in the sera of patients with systemic lupus erythematosus (SLE) but only at a low frequency (24%) and concentration in normal sera. The level of 4.6.3 ID in SLE did not correlate with serum IgM and IgG nor with anti-DNA antibody concentrations. Idiotypic relatedness between SLE serum antibodies and monoclonal anti-DNA antibodies of normals implies the existence of a cross-reactive idiotype family and implies that a conserved common gene or closely related genes exist in the germ line encoding these 4.6.3 ID positive antibodies some of which are not exclusively associated with nucleic acid reactivity. The expression of these germ line genes in vivo thus distinguishes SLE from normals.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andrzejewski C., Jr, Rauch J., Lafer E., Stollar B. D., Schwartz R. S. Antigen-binding diversity and idiotypic cross-reactions among hybridoma autoantibodies to DNA. J Immunol. 1981 Jan;126(1):226–231. [PubMed] [Google Scholar]
- André-Schwartz J., Datta S. K., Shoenfeld Y., Isenberg D. A., Stollar B. D., Schwartz R. S. Binding of cytoskeletal proteins by monoclonal anti-DNA lupus autoantibodies. Clin Immunol Immunopathol. 1984 May;31(2):261–271. doi: 10.1016/0090-1229(84)90246-0. [DOI] [PubMed] [Google Scholar]
- Atkinson P. M., Lampman G. W., Furie B. C., Naparstek Y., Schwartz R. S., Stollar B. D., Furie B. 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. J Clin Invest. 1985 Apr;75(4):1138–1143. doi: 10.1172/JCI111808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bell D. A., Cairns E., Cikalo K., Ly V., Block J., Pruzanski W. Antinucleic acid autoantibody responses of normal human origin: antigen specificity and idiotypic characteristics compared to patients with systemic lupus erythematosus and patients with monoclonal IgM. J Rheumatol Suppl. 1987 Jun;14 (Suppl 13):127–131. [PubMed] [Google Scholar]
- Cairns E., Block J., Bell D. A. Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin. J Clin Invest. 1984 Sep;74(3):880–887. doi: 10.1172/JCI111505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns E., Komar R., Bell D. A. Cytoskeletal binding of monoclonal anti-DNA antibodies derived from tonsillar lymphoid cells of a normal subject. Arthritis Rheum. 1986 Nov;29(11):1351–1358. doi: 10.1002/art.1780291107. [DOI] [PubMed] [Google Scholar]
- Cairns E., St Germain J., Bell D. A. The in vitro production of anti-DNA antibody by cultured peripheral blood or tonsillar lymphoid cells from normal donors and SLE patients. J Immunol. 1985 Dec;135(6):3839–3844. [PubMed] [Google Scholar]
- Datta S. K., Naparstek Y., Schwartz R. S. In vitro production of an anti-DNA idiotype by lymphocytes of normal subjects and patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1986 Mar;38(3):302–318. doi: 10.1016/0090-1229(86)90240-0. [DOI] [PubMed] [Google Scholar]
- Datta S. K., Stollar B. D., Schwartz R. S. Normal mice express idiotypes related to autoantibody idiotypes of lupus mice. Proc Natl Acad Sci U S A. 1983 May;80(9):2723–2727. doi: 10.1073/pnas.80.9.2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dersimonian H., Schwartz R. S., Barrett K. J., Stollar B. D. Relationship of human variable region heavy chain germ-line genes to genes encoding anti-DNA autoantibodies. J Immunol. 1987 Oct 1;139(7):2496–2501. [PubMed] [Google Scholar]
- Fish F., Ziff M. Hidden anti-double stranded DNA antibodies in autoimmune mice. Clin Exp Immunol. 1982 Sep;49(3):587–597. [PMC free article] [PubMed] [Google Scholar]
- Fish F., Ziff M. The in vitro and in vivo induction of anti-double-stranded DNA antibodies in normal and autoimmune mice. J Immunol. 1982 Jan;128(1):409–414. [PubMed] [Google Scholar]
- Halpern R., Davidson A., Lazo A., Solomon G., Lahita R., Diamond B. Familial systemic lupus erythematosus. Presence of a cross-reactive idiotype in healthy family members. J Clin Invest. 1985 Aug;76(2):731–736. doi: 10.1172/JCI112028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halpern R., Schiffenbauer J., Solomon G., Diamond B. Detection of masked anti-DNA antibodies in lupus sera by a monoclonal anti-idiotype. J Immunol. 1984 Oct;133(4):1852–1856. [PubMed] [Google Scholar]
- Hoch S., Schur P. H., Schwaber J. Frequency of anti-DNA antibody producing cells from normals and patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1983 Apr;27(1):28–37. doi: 10.1016/0090-1229(83)90053-3. [DOI] [PubMed] [Google Scholar]
- Hoch S., Schwaber J. Specificity analysis of human anti-DNA antibodies. J Immunol. 1986 Feb 1;136(3):892–897. [PubMed] [Google Scholar]
- Isenberg D. A., Collins C. Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients. J Clin Invest. 1985 Jul;76(1):287–294. doi: 10.1172/JCI111959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isenberg D. A., Shoenfeld Y., Madaio M. P., Rauch J., Reichlin M., Stollar B. D., Schwartz R. S. Anti-DNA antibody idiotypes in systemic lupus erythematosus. Lancet. 1984 Aug 25;2(8400):417–422. doi: 10.1016/s0140-6736(84)92904-0. [DOI] [PubMed] [Google Scholar]
- Isenberg D., Dudeney C., Wojnaruska F., Bhogal B. S., Rauch J., Schattner A., Naparstek Y., Duggan D. Detection of cross reactive anti-DNA antibody idiotypes on tissue-bound immunoglobulins from skin biopsies of lupus patients. J Immunol. 1985 Jul;135(1):261–264. [PubMed] [Google Scholar]
- Kofler R., Noonan D. J., Levy D. E., Wilson M. C., Møller N. P., Dixon F. J., Theofilopoulos A. N. Genetic elements used for a murine lupus anti-DNA autoantibody are closely related to those for antibodies to exogenous antigens. J Exp Med. 1985 Apr 1;161(4):805–815. doi: 10.1084/jem.161.4.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Margolies M. N., Juszczak E. C., Near R., Marshak-Rothstein A., Rothstein T. L., Sato V. L., Siekevitz M., Smith J. A., Wysocki L. J., Gefter M. L. Structural correlates of idiotypy in the arsonate system. Ann N Y Acad Sci. 1983;418:48–64. doi: 10.1111/j.1749-6632.1983.tb18054.x. [DOI] [PubMed] [Google Scholar]
- Mayus J. L., Pisetsky D. S. Expression of a highly conserved anti-DNA idiotype in normal and autoimmune mice. Clin Immunol Immunopathol. 1985 Mar;34(3):366–378. doi: 10.1016/0090-1229(85)90185-0. [DOI] [PubMed] [Google Scholar]
- Naparstek Y., André-Schwartz J., Manser T., Wysocki L. J., Breitman L., Stollar B. D., Gefter M., Schwartz R. S. A single germline VH gene segment of normal A/J mice encodes autoantibodies characteristic of systemic lupus erythematosus. J Exp Med. 1986 Aug 1;164(2):614–626. doi: 10.1084/jem.164.2.614. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pancer L. B., Bell D. A., Singhal S. K. Induction of anti-ssDNA antibodies in normal and preautoimmune mice in vivo. J Immunol. 1980 Feb;124(2):939–946. [PubMed] [Google Scholar]
- Pancer L. B., Milazzo M. F., Morris V. L., Singhal S. K., Bell D. A. Immunogenicity and characterization of supernatant DNA released by murine spleen cells. J Immunol. 1981 Jul;127(1):98–104. [PubMed] [Google Scholar]
- Rauch J., Massicotte H., Tannenbaum H. Hybridoma anti-DNA autoantibodies from patients with rheumatoid arthritis and systemic lupus erythematosus demonstrate similar nucleic acid binding characteristics. J Immunol. 1985 Jan;134(1):180–186. [PubMed] [Google Scholar]
- Rauch J., Murphy E., Roths J. B., Stollar B. D., Schwartz R. S. A high frequency idiotypic marker of anti-DNA autoantibodies in MRL-Ipr/Ipr mice. J Immunol. 1982 Jul;129(1):236–241. [PubMed] [Google Scholar]
- Rauch J., Murphy E., Roths J. B., Stollar B. D., Schwartz R. S. A high frequency idiotypic marker of anti-DNA autoantibodies in MRL-Ipr/Ipr mice. J Immunol. 1982 Jul;129(1):236–241. [PubMed] [Google Scholar]
- Schattner A., Duggan D., Naparstek Y., Schwartz R. S. Effects of interferon-alpha on the expression of a lupus idiotype in normal humans. Clin Immunol Immunopathol. 1986 Mar;38(3):327–336. doi: 10.1016/0090-1229(86)90242-4. [DOI] [PubMed] [Google Scholar]
- Shoenfeld Y., Isenberg D. A., Rauch J., Madaio M. P., Stollar B. D., Schwartz R. S. Idiotypic cross-reactions of monoclonal human lupus autoantibodies. J Exp Med. 1983 Sep 1;158(3):718–730. doi: 10.1084/jem.158.3.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shoenfeld Y., Isenberg D. A., Rauch J., Madaio M. P., Stollar B. D., Schwartz R. S. Idiotypic cross-reactions of monoclonal human lupus autoantibodies. J Exp Med. 1983 Sep 1;158(3):718–730. doi: 10.1084/jem.158.3.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shoenfeld Y., Rauch J., Massicotte H., Datta S. K., André-Schwartz J., Stollar B. D., Schwartz R. S. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med. 1983 Feb 24;308(8):414–420. doi: 10.1056/NEJM198302243080802. [DOI] [PubMed] [Google Scholar]
- Solomon G., Schiffenbauer J., Keiser H. D., Diamond B. Use of monoclonal antibodies to identify shared idiotypes on human antibodies to native DNA from patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1983 Feb;80(3):850–854. doi: 10.1073/pnas.80.3.850. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tron F., Le Guern C., Cazenave P. A., Bach J. F. Intrastrain recurrent idiotypes among anti-DNA antibodies of (NZB x NZW)F1 hybrid mice. Eur J Immunol. 1982 Sep;12(9):761–766. doi: 10.1002/eji.1830120911. [DOI] [PubMed] [Google Scholar]
- el-Roiey A., Gross W. L., Luedemann J., Isenberg D. A., Shoenfeld Y. Preferential secretion of a common anti-DNA idiotype (16/6 Id) and anti-polynucleotide antibodies by normal mononuclear cells following stimulation with Klebsiella pneumoniae. Immunol Lett. 1986 Jun;12(5-6):313–319. doi: 10.1016/0165-2478(86)90036-2. [DOI] [PubMed] [Google Scholar]