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. 1994 May;96(2):317–322. doi: 10.1111/j.1365-2249.1994.tb06560.x

Autoantibodies from mixed cryoglobulinaemia patients bind glomerular antigens.

M P Dolcher 1, B Marchini 1, A Sabbatini 1, G Longombardo 1, C Ferri 1, L Riente 1, S Bombardieri 1, P Migliorini 1
PMCID: PMC1534894  PMID: 8187340

Abstract

Mixed cryoglobulinaemia (MC) is a disorder characterized by the presence of large amounts of cryoprecipitating IgM-IgG complexes. An immune complex glomerulonephritis develops in one third of all patients, but its occurrence does not seem related to the amount of cryoglobulins in the sera, nor to their complement-fixing ability. In this study we investigated the presence of IgG antibodies reactive with kidney antigens in 33 MC patients (11 with glomerulonephritis, 22 without renal involvement). A total glomerular extract was run on a 10% acrylamide gel, blotted to nitrocellulose and probed with the patients' sera. Sera from half of the patients without renal involvement reacted with several glomerular antigens whose molecular weight ranged between 200 and 29 kD. In the group with renal involvement, sera from 7/11 patients reacted with an antigen of 50 kD, which is also expressed in thymus, but not in the heart or liver. In a follow-up study of four patients with renal involvement, the amount of serum antibody specific for the 50-kD antigen fluctuated, either spontaneously or in response to therapy. These results show that antibodies specific for glomerular antigens are detectable in MC sera. The immune response against a 50-kD antigen expressed in the kidney and thymus seems to be restricted to a subset of MC patients with renal involvement. Circulating autoantibodies specific for glomerular antigens might contribute to the induction of glomerulonephritis in MC forming immune complexes in situ.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ben-Bassat M., Boner G., Rosenfeld J., Pick A. I., Kahana M., Hazaz B., Hochman B. The clinicopathologic features of cryoglobulinemic nephropathy. Am J Clin Pathol. 1983 Feb;79(2):147–156. doi: 10.1093/ajcp/79.2.147. [DOI] [PubMed] [Google Scholar]
  2. Blake M. S., Johnston K. H., Russell-Jones G. J., Gotschlich E. C. A rapid, sensitive method for detection of alkaline phosphatase-conjugated anti-antibody on Western blots. Anal Biochem. 1984 Jan;136(1):175–179. doi: 10.1016/0003-2697(84)90320-8. [DOI] [PubMed] [Google Scholar]
  3. Carnemolla B., Balza E., Siri A., Zardi L., Nicotra M. R., Bigotti A., Natali P. G. A tumor-associated fibronectin isoform generated by alternative splicing of messenger RNA precursors. J Cell Biol. 1989 Mar;108(3):1139–1148. doi: 10.1083/jcb.108.3.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cordonnier D., Martin H., Groslambert P., Micouin C., Chenais F., Stoebner P. Mixed IgG-IgM cryoglobulinemia with glomerulonephritis. Immunochemical, fluorescent and ultrastructural study of kidney and in vitro cryoprecipitate. Am J Med. 1975 Dec;59(6):867–872. doi: 10.1016/0002-9343(75)90480-5. [DOI] [PubMed] [Google Scholar]
  5. Druet P., Letonturier P., Contet A., Mandet C. Cryoglobulinaemia in human renal diseases. A study of seventy-six cases. Clin Exp Immunol. 1973 Dec;15(4):483–496. [PMC free article] [PubMed] [Google Scholar]
  6. Ebling F., Hahn B. H. Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus. Comparison of antibodies in serum and renal eluates. Arthritis Rheum. 1980 Apr;23(4):392–403. doi: 10.1002/art.1780230402. [DOI] [PubMed] [Google Scholar]
  7. Faaber P., Rijke T. P., van de Putte L. B., Capel P. J., Berden J. H. Cross-reactivity of human and murine anti-DNA antibodies with heparan sulfate. The major glycosaminoglycan in glomerular basement membranes. J Clin Invest. 1986 Jun;77(6):1824–1830. doi: 10.1172/JCI112508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feizi T., Gitlin N. Immune-complex disease of the kidney associated with chronic hepatitis and cryoglobulinaemia. Lancet. 1969 Oct 25;2(7626):873–876. doi: 10.1016/s0140-6736(69)92329-0. [DOI] [PubMed] [Google Scholar]
  9. Ferri C., La Civita L., Longombardo G., Greco F., Bombardieri S. Hepatitis C virus and mixed cryoglobulinaemia. Eur J Clin Invest. 1993 Jul;23(7):399–405. doi: 10.1111/j.1365-2362.1993.tb00782.x. [DOI] [PubMed] [Google Scholar]
  10. Ferri C., Moriconi L., Gremignai G., Migliorini P., Paleologo G., Fosella P. V., Bombardieri S. Treatment of the renal involvement in mixed cryoglobulinemia with prolonged plasma exchange. Nephron. 1986;43(4):246–253. doi: 10.1159/000183849. [DOI] [PubMed] [Google Scholar]
  11. Gauthier V. J., Mannik M., Striker G. E. Effect of cationized antibodies in performed immune complexes on deposition and persistence in renal glomeruli. J Exp Med. 1982 Sep 1;156(3):766–777. doi: 10.1084/jem.156.3.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gavalchin J., Nicklas J. A., Eastcott J. W., Madaio M. P., Stollar B. D., Schwartz R. S., Datta S. K. Lupus prone (SWR x NZB)F1 mice produce potentially nephritogenic autoantibodies inherited from the normal SWR parent. J Immunol. 1985 Feb;134(2):885–894. [PubMed] [Google Scholar]
  13. Gyotoku Y., Abdelmoula M., Spertini F., Izui S., Lambert P. H. Cryoglobulinemia induced by monoclonal immunoglobulin G rheumatoid factors derived from autoimmune MRL/MpJ-lpr/lpr mice. J Immunol. 1987 Jun 1;138(11):3785–3792. [PubMed] [Google Scholar]
  14. Jacob L., Lety M. A., Louvard D., Bach J. F. Binding of a monoclonal anti-DNA autoantibody to identical protein(s) present at the surface of several human cell types involved in lupus pathogenesis. J Clin Invest. 1985 Jan;75(1):315–317. doi: 10.1172/JCI111692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kefalides N. A., Pegg M. T., Ohno N., Poon-King T., Zabriskie J., Fillit H. Antibodies to basement membrane collagen and to laminin are present in sera from patients with poststreptococcal glomerulonephritis. J Exp Med. 1986 Mar 1;163(3):588–602. doi: 10.1084/jem.163.3.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kraus W., Dale J. B., Beachey E. H. Identification of an epitope of type 1 streptococcal M protein that is shared with a 43-kDa protein of human myocardium and renal glomeruli. J Immunol. 1990 Dec 15;145(12):4089–4093. [PubMed] [Google Scholar]
  17. Lawley T. J., Gorevic P. D., Hamburger M. I., Franklin E. C., Frank M. M. Multiple types of immune complexes in patients with mixed cryoglobulinemia. J Invest Dermatol. 1980 Oct;75(4):297–301. doi: 10.1111/1523-1747.ep12530883. [DOI] [PubMed] [Google Scholar]
  18. Madaio M. P., Carlson J., Cataldo J., Ucci A., Migliorini P., Pankewycz O. Murine monoclonal anti-DNA antibodies bind directly to glomerular antigens and form immune deposits. J Immunol. 1987 May 1;138(9):2883–2889. [PubMed] [Google Scholar]
  19. Madaio M. P., Salant D. J., Adler S., Darby C., Couser W. G. Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane. Kidney Int. 1984 Oct;26(4):397–403. doi: 10.1038/ki.1984.188. [DOI] [PubMed] [Google Scholar]
  20. Meltzer M., Franklin E. C., Elias K., McCluskey R. T., Cooper N. Cryoglobulinemia--a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med. 1966 Jun;40(6):837–856. doi: 10.1016/0002-9343(66)90200-2. [DOI] [PubMed] [Google Scholar]
  21. Migliorini P., Riente L., Manca F., Celada F., Bombardieri S. Cold-precipitable immune complexes in collagen diseases: evidence for the coexistence of multiple types of circulating complexes in the same serum. Clin Immunol Immunopathol. 1983 Oct;29(1):129–140. doi: 10.1016/0090-1229(83)90014-4. [DOI] [PubMed] [Google Scholar]
  22. O'Donoghue D. J., Darvill A., Ballardie F. W. Mesangial cell autoantigens in immunoglobulin A nephropathy and Henoch-Schönlein purpura. J Clin Invest. 1991 Nov;88(5):1522–1530. doi: 10.1172/JCI115462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pankewycz O. G., Migliorini P., Madaio M. P. Polyreactive autoantibodies are nephritogenic in murine lupus nephritis. J Immunol. 1987 Nov 15;139(10):3287–3294. [PubMed] [Google Scholar]
  24. Reininger L., Berney T., Shibata T., Spertini F., Merino R., Izui S. Cryoglobulinemia induced by a murine IgG3 rheumatoid factor: skin vasculitis and glomerulonephritis arise from distinct pathogenic mechanisms. Proc Natl Acad Sci U S A. 1990 Dec;87(24):10038–10042. doi: 10.1073/pnas.87.24.10038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schwartz R. S., Stollar B. D. Origins of anti-DNA autoantibodies. J Clin Invest. 1985 Feb;75(2):321–327. doi: 10.1172/JCI111704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stott D. I. Immunoblotting and dot blotting. J Immunol Methods. 1989 May 12;119(2):153–187. doi: 10.1016/0022-1759(89)90394-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zimmerman S. W., Dreher W. H., Burkholder P. M., Goldfarb S., Weinstein A. B. Nephropathy and mixed cryoglobulinemia: evidence for an immune complex pathogenesis. Nephron. 1976;16(2):103–115. doi: 10.1159/000180591. [DOI] [PubMed] [Google Scholar]

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