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. 1976 Aug;25(2):212–226.

Detection of circulating antigen-antibody complexes by their inhibitory effect on the agglutination of IgG-coated particles by rheumatioid factor of Clq.

A Z Lurhuma, C L Cambiaso, P L Masson, J F Heremans
PMCID: PMC1541367  PMID: 954232

Abstract

The agglutination of Ig-coated particles by human RF or Clq can be inhibited by Ig aggregates or AgAb complexes. The effect of Ig class was studied by means of agarose-linked human monoclonal Igs. RF was inhibited by all subclasses of IgG and IgA but not by IgM, whereas Clq reacted with IgM, IgG3 and IgG1. Heat-aggregated IgG3 was fractionated by gel-filtration on Ultrogel. Inhibition was restricted to certain fractions of aggregates, viz (IgG3) approximately 7 and (IgG3) approximately 21 for RF, and (IgG3) approximately 10, (IgG3) approximately 14 and (IgG3) approximately 27 for Clq. In a precipitin curve experiment, it was found that RF was inhibited by soluble complexes over an extended range of AgAb ratios, the inactivation of Clq being limited to complexes with 2-5 times antigen excess. Inhibiting factors were found in patients with various diseases and, at low titres, in 22% of healthy people. In 27% of patients' sera, the inhibitors were demonstrable by Clq only after removal of endogenous RF by adsorption on insolubilized IgG. In several patients endogenous agglutinating activity and direct inhibitory activity tended to alternate during the course of the disease. Sera from various patients were also filtrated on Ultrogel and the elution was monitored by immunoassay of IgA, IgM and IgG, as well as by the two inhibition tests. The inhibiting factors were distributed over several peaks which only partially coincided with the elution profiles of IgG and IgM.

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Selected References

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  1. Agnello V., Winchester R. J., Kunkel H. G. Precipitin reactions of the C1q component of complement with aggregated gamma-globulin and immune complexes in gel diffusion. Immunology. 1970 Dec;19(6):909–919. [PMC free article] [PubMed] [Google Scholar]
  2. Almeida J. D., Waterson A. P. Immune complexes in hepatitis. Lancet. 1969 Nov 8;2(7628):983–986. doi: 10.1016/s0140-6736(69)90540-6. [DOI] [PubMed] [Google Scholar]
  3. Alpert E., Isselbacher K. J., Schur P. H. The pathogenesis of arthritis associated with viral hepatitis. Complement-component studies. N Engl J Med. 1971 Jul 22;285(4):185–189. doi: 10.1056/NEJM197107222850401. [DOI] [PubMed] [Google Scholar]
  4. Andres G. A., Accinni L., Hsu K. C., Zabriskie J. B., Seegal B. C. Electron microscopic studies of human glomerulonephritis with ferritin-conjugated antibody. Localization of antigen-antibody complexes in glomerular structures of patients with acute glomerulonephritis. J Exp Med. 1966 Feb 1;123(2):399–412. doi: 10.1084/jem.123.2.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Aronsen K. F., Ekelund G., Kindmark C. O., Laurell C. B. Sequential changes of plasma proteins after surgical trauma. Scand J Clin Lab Invest Suppl. 1972;124:127–136. doi: 10.3109/00365517209102760. [DOI] [PubMed] [Google Scholar]
  6. Baldini M. G. Idiopathic thrombocytopenic purpura and the ITP syndrome. Med Clin North Am. 1972 Jan;56(1):47–64. doi: 10.1016/s0025-7125(16)32422-1. [DOI] [PubMed] [Google Scholar]
  7. Baldwin R. W., Price M. R., Robins R. A. Blocking of lymphocyte-mediated cytotoxicity for rat hepatoma cells by tumour-specific antigen-antibody complexes. Nat New Biol. 1972 Aug 9;238(84):185–186. doi: 10.1038/newbio238185a0. [DOI] [PubMed] [Google Scholar]
  8. Cambiaso C. L., Goffinet A., Vaerman J. P., Heremans J. F. Glutaraldehyde-activated aminohexyl- derivative of Sepharose 4B as a new verstile immunoabsorbent. Immunochemistry. 1975 Apr;12(4):273–278. doi: 10.1016/0019-2791(75)90175-5. [DOI] [PubMed] [Google Scholar]
  9. Capra J. D., Kunkel H. G. Aggregation of gamma-G3 proteins: relevance to the hyperviscosity syndrome. J Clin Invest. 1970 Mar;49(3):610–621. doi: 10.1172/JCI106272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chan T. K., Todd D. Haemolysis complicating viral hepatitis in patients with glucose-6-phosphate dehydrogenase deficiency. Br Med J. 1975 Jan 18;1(5950):131–133. doi: 10.1136/bmj.1.5950.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cowdery J. S., Jr, Treadwell P. E., Fritz R. B. A radioimmunoassay for human antigen-antibody complexes in clinical material. J Immunol. 1975 Jan;114(1 Pt 1):5–9. [PubMed] [Google Scholar]
  12. Doe W. F., Booth C. C., Brown D. L. Evidence for complement-binding immune complexes in adult coeliac disease, Crohn's disease, and ulcerative colitis. Lancet. 1973 Feb 24;1(7800):402–403. doi: 10.1016/s0140-6736(73)90254-7. [DOI] [PubMed] [Google Scholar]
  13. Ewald R. W., Schubart A. F. Agglutinating activity of the complement component C'1q in the F-II latex fixation test. J Immunol. 1966 Jul;97(1):100–105. [PubMed] [Google Scholar]
  14. GRUBB R. Agglutination of erythrocytes coated with incomplete anti-Rh by certain rheumatoid arthritic sera and some other sera; the existence of human serum groups. Acta Pathol Microbiol Scand. 1956;39(3):195–197. [PubMed] [Google Scholar]
  15. Ishizaka T., Ishizaka K., Salmon S., Fudenberg H. Biologic activities of aggregated gamma-globulin. 8. Aggregated immunoglobulins of different classes. J Immunol. 1967 Jul;99(1):82–91. [PubMed] [Google Scholar]
  16. Jewell D. P., MacLennan I. C. Circulating immune complexes in inflammatory bowel disease. Clin Exp Immunol. 1973 Jun;14(2):219–226. [PMC free article] [PubMed] [Google Scholar]
  17. Johnson A. H., Mowbray J. F., Porter K. A. Detection of circulating immune complexes in pathological human sera. Lancet. 1975 Apr 5;1(7910):762–765. doi: 10.1016/s0140-6736(75)92433-2. [DOI] [PubMed] [Google Scholar]
  18. KUNKEL H. G., MULLER-EBERHARD H. J., FUDENBERG H. H., TOMASI T. B. Gamma globulin complexes in rheumatoid arthritis and certain other conditions. J Clin Invest. 1961 Jan;40:117–129. doi: 10.1172/JCI104224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Karpatkin S., Garg S. K., Siskind G. W. Autoimmune thrombocytopenic purpura and the compensated thrombocytolytic state. Am J Med. 1971 Jul;51(1):1–4. doi: 10.1016/0002-9343(71)90317-2. [DOI] [PubMed] [Google Scholar]
  20. Lachmann P. J., Thompson R. A. Reactive lysis: the complement-mediated lysis of unsensitized cells. II. The characterization of activated reactor as C56 and the participation of C8 and C9. J Exp Med. 1970 Apr 1;131(4):643–657. doi: 10.1084/jem.131.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ludwig F. J., Cusumano C. L. Detection of immune complexes using 125I goat anti(human IgG) monovalent (Fab') antibody fragments. J Natl Cancer Inst. 1974 May;52(5):1529–36. doi: 10.1093/jnci/52.5.1529. [DOI] [PubMed] [Google Scholar]
  22. MULLER-EBERHARD H. J., KUNKEL H. G. Isolation of a thermolabile serum protein which precipitates gamma-globulin aggregates and participates in immune hemolysis. Proc Soc Exp Biol Med. 1961 Feb;106:291–295. doi: 10.3181/00379727-106-26313. [DOI] [PubMed] [Google Scholar]
  23. Michael A. F., Jr, Drummond K. N., Good R. A., Vernier R. L. Acute poststreptococcal glomerulonephritis: immune deposit disease. J Clin Invest. 1966 Feb;45(2):237–248. doi: 10.1172/JCI105336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Munthe E., Natvig J. B. Characterization of IgG complexes in eluates from rheumatoid tissue. Clin Exp Immunol. 1971 Feb;8(2):249–262. [PMC free article] [PubMed] [Google Scholar]
  25. Nydegger U. E., Lambert P. H., Gerber H., Miescher P. A. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. Quantitation by binding to radiolabeled C1q. J Clin Invest. 1974 Aug;54(2):297–309. doi: 10.1172/JCI107765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. PITCHER C. S., WILLIAMS R. Reduced red cell survival in jaundice and its relation to abnormal glutathione metabolism. Clin Sci. 1963 Apr;24:239–252. [PubMed] [Google Scholar]
  27. Penttinen K., Vaheri A., Myllylä G. Detection and characterization of immune complexes by the platelet aggregation test. I. Complexes formed in vitro. Clin Exp Immunol. 1971 Mar;8(3):389–397. [PMC free article] [PubMed] [Google Scholar]
  28. ROTHBERG R. M., FARR R. S. ANTI-BOVINE SERUM ALBUMIN AND ANTI-ALPHA LACTALBUMIN IN THE SERUM OF CHILDREN AND ADULTS. Pediatrics. 1965 Apr;35:571–588. [PubMed] [Google Scholar]
  29. Rivat L., Rivat C., Ropartz C. Anti-immunoglobulines humaines. Présence d'anti-IgD et d'anti-IgA dans les sérums humains. Rev Fr Transfus. 1973 Sep;16(3):279–287. doi: 10.1016/s0035-2977(73)80066-5. [DOI] [PubMed] [Google Scholar]
  30. Saluk P. H., Clem L. W. The unique molecular weight of the heavy chain from human IgG3. J Immunol. 1971 Jul;107(1):298–301. [PubMed] [Google Scholar]
  31. Shulman N. R., Barker L. F. Virus-like antigen, antibody, and antigen-antibody complexes in hepatitis measured by complement fixation. Science. 1969 Jul 18;165(3890):304–306. doi: 10.1126/science.165.3890.304. [DOI] [PubMed] [Google Scholar]
  32. Shulman N. R., Marder V. J., Weinrach R. S. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies. Ann N Y Acad Sci. 1965 Jun 30;124(2):499–542. doi: 10.1111/j.1749-6632.1965.tb18984.x. [DOI] [PubMed] [Google Scholar]
  33. Sjögren H. O., Hellström I., Bansal S. C., Hellström K. E. Suggestive evidence that the "blocking antibodies" of tumor-bearing individuals may be antigen--antibody complexes. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1372–1375. doi: 10.1073/pnas.68.6.1372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. TARANTA A., WEISS H. S., FRANKLIN E. C. Precipitating factor for aggregated gamma-globulins in normal human sera. Nature. 1961 Jan 21;189:239–240. doi: 10.1038/189239a0. [DOI] [PubMed] [Google Scholar]
  35. Tan E. M., Schur P. H., Carr R. I., Kunkel H. G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. doi: 10.1172/JCI105479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Theofilopoulos A. N., Wilson C. B., Bokisch V. A., Dixon F. J. Binding of soluble immune complexes to human lymphoblastoid cells. II. Use of Raji cells to detect circulating immune complexes in animal and human sera. J Exp Med. 1974 Nov 1;140(5):1230–1244. doi: 10.1084/jem.140.5.1230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. WILLIAMS R. C., Jr, KUNKEL H. G. Antibodies to rabbit gamma-globulin after immunizing with various preparations of autologous gamma-globulin. Proc Soc Exp Biol Med. 1963 Mar;112:554–561. doi: 10.3181/00379727-112-28104. [DOI] [PubMed] [Google Scholar]
  38. Williams R. C., Jr, Griffiths R. W., Emmons J. D., Field R. C. Naturally occurring human antiglobulins with specificity for E. J Clin Invest. 1972 Apr;51(4):955–963. doi: 10.1172/JCI106890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yonemasu K., Stroud R. M. Clq: rapid purification method for preparation of monospecific antisera and for biochemical studies. J Immunol. 1971 Feb;106(2):304–313. [PubMed] [Google Scholar]

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