Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1991 Nov;82(11):1284–1291. doi: 10.1111/j.1349-7006.1991.tb01794.x

Prognostic Significance of Circulating Immune Complexes in Cancer Patients

Tushar Kanti Dass 1, Mehar Aziz 1,, Ashok Ashok 2
PMCID: PMC5918336  PMID: 1752784

Abstract

Circulating immune complexes (CIC) were estimated in 100 cancer patients and 25 healthy control volunteers by means of the polyethylene glycol (PEG) precipitation test and latex agglutination inhibition (LAI) test. Pathological levels of CIC were found in 47% of the patients by PEG precipitation test and in 59% of the patients by LAI test; both tests were positive in 33% of the patients. Consequently, the use of the two assays resulted in 73% seropositivity for CIC. The PEG precipitation test detects antigen‐antibody complexes formed in the ratio of 2:1 (Ag2Ab), while the LAI test could detect immune complexes formed over an extended range of antigen‐antibody ratio including complexes as small as SS. CIC values were significantly higher by combined assays (P < 0.001) as compared to individual assays (P < 0.01) when compared with the control group. It was found that 75% of post‐operative follow‐up patients became seronegative for CIC in the combined assays, whereas the 25% of post‐operative patients who remained seropositive for CIC showed recurrence within three months after surgery. Immune‐complex deposition was demonstrated on malignant cells in vitro by direct immunofluorescence studies in 73.3% of patients, while 60% of patients revealed complement‐fixing antigen‐antibody complexes. It was found that 20% of patients showing positive immunofluorescence with anti‐C3‐antisera had decreased levels of CIC. Complement‐mediated cytotoxic injury results in reduction of tumor cell mass and subsequent decrease in CIC. Necrotizing and leucocytoclastic vasculitis in the tumor mass was initiated by raised CIC levels in vivo in 71% of patients. Necrosis of malignant tumors was seen in 58% of patients, and hemorrhage in 36% of patients. These changes were considered to be an aftermath of immuno‐complex vasculitis initiated by CIC.

Keywords: Immune complex, Cancer patient

Full Text

The Full Text of this article is available as a PDF (733.8 KB).

REFERENCES

  • 1. ) Sjogren , H. O. , Hellstrom , I. , Bansal , S. E. and Hellstrom , K. E.Suggestive evidence that the blocking antibodies of tumor bearing individuals may be antigen‐antibody complexes . Proc. Natl. Acad. Sci. USA , 68 , 1372 – 1377 ( 1971. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) Theofilopoulos , A. M. , Andrews , B. S. , Urist , M. M. , Morton , D. L. , and Dixon , F. J.The nature of immune complexes in human sera . J. Immunol. , 119 , 657 – 662 ( 1977. ). [PubMed] [Google Scholar]
  • 3. ) Samayoa , E. A. , McDuffe , F. , Nelson , A. M. , Go , V. L. W. , Luthra , M. S. and Brumfield , H.W. Immunoglobulin complexes in sera of patients with malignancy . Int. J. Cancer , 19 , 12 – 17 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Baldwin , R. W. , Embleton , M. , Price , M. and Pobins , R.Immunity in tumor bearing host and its modifications in serum factors . Cancer , 34 , 1452 – 1460 ( 1974. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Amlot , P. , Slancy , J. and Williams , B.Circulating immune complexes and symptoms in Hodgkin's disease . Lancet , 7 , 449 – 451 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Carpentier , N. A. , Lange , G. T. , Fiere , D. M. , Fournie , G. J. , Lambert , P. M. and Meischer , P. A.Clinical relevance of circulating immune complexes in human leukemia . J. Clin. Invest. , 60 , 874 – 884 ( 1977. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Hoffken , K. , Meredith , I. D. , Robins , R. A. , Baldwin , R. W. , Davies , C. J. and Blamey , R. W.Circulating immune complexes in patients with breast cancer . Br. Med. J. , 2 , 218 – 220 ( 1977. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Herberman , R. B. , Bordes , M. , Lambert , P. H. , Luthra , H. S. , Robins , R. A. , Sizari , P. and Theofilopoulos , A.Report on international comparative evaluation of possible value of assays for immune complexes for diagnosis of human breast cancer . Int. J. Cancer , 27 , 569 – 576 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Horvath , M. , Fekete , B. and Rahoty , P.Investigation of circulating immune complexes in patients with breast cancer . Oncology , 39 , 20 – 22 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Katyal , P. , Kundu , S. and Bose , M.Circulating immune complexes in breast cancer . Indian J. Med. Microbiol , 4 , 153 – 158 ( 1986. ). [PubMed] [Google Scholar]
  • 11. ) Dorosevich , A.Circulating and tumor‐tissue bound immune‐complexes in patients with breast cancer . Arch. Pathol. , 45 , 30 – 34 ( 1983. ). [PubMed] [Google Scholar]
  • 12. ) Jose , D. and Seshadri , R.Circulating immune complexes in human neuroblastoma: direct assay and role in blocking specific cellular immunity . Int. J. Cancer , 13 , 824 – 838 ( 1974. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Fust , G. , Fekete , B. , Angyal , L , Jakab , A. , Pal , A. , Meretey , K. , Falus , A. , Torok , K. , Szegedi , G. Y. , Kavai , M. , Puskas , E. , CsecsiNagy , M. , Szabo , T. , Lenkey , A. and Misz , M.Evaluation of different methods for detecting circulating immune complexes. Studies in patients with lung cancer . J. Immunol. Methods , 46 , 259 – 276 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Seth , P. , Balachandran , N. , Malviya , A. N. and Kumar , R.Circulating immune complexes in carcinoma of uterine cervix . Clin. Exp. Immunol , 38 , 77 – 82 ( 1979. ). [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Beaufort , F. , Auner , M. and Lahousen , M.Sequential determination of circulating immune complexes in ovarian tumors . Wien. Med. Wochenschr. , 136 , 317 – 322 ( 1986. ). [PubMed] [Google Scholar]
  • 16. ) Beaufils , H. , Patte , R. and Aubert , P.Renal immunopathology in renal cell carcinoma . Virchows Arch. A , 404 , 87 – 93 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Krajina , Z. and Bolanca , S.Tumor antigens and immune‐complexes in laryngeal cancer . Orient. J. Otorhinolaryngol. Relat. Spe. , 47 , 119 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Denaro , A. , Caruno , R. , Rossi , M. , D'Arrigo , C. , Malapontes , G. , Mazzarino , M. C. and Cutrona , D.Circulating immune‐complexes in laryngeal carcinoma . Arch. Otolaryngol. , 111 , 595 – 597 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Mukhopadhyaya , R. , Rao , R. , Fakih , D. and Gangal , S.Detection of circulating immune complexes in patients with squamous cell carcinoma of oval cavity . J. Clin. Lab. Immunol. , 21 , 189 – 194 ( 1986. ). [PubMed] [Google Scholar]
  • 20. ) Steele , G. , Sonis , S. , Stelos , P. , Rittgers , R. , Zamchek , W. , Finn , D. , Malts , J. , Mayer , R. , Lokich , J. and Wilson , R. E.Circulating immune complexes in patients following clinically curative resection of colorectal cancer . Surgery , 83 , 648 – 654 ( 1978. ). [PubMed] [Google Scholar]
  • 21. ) Rossen , R. D. and Barnes , B. C.Measuring serum immune complexes in cancer . Ann. Intern. Med. , 88 , 570 – 576 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Creighton , W. D. , Lambert , P. H. and Miescher , P. A.Detection of antibodies and soluble antigen‐antibody complexes by precipitation with polyethylene glycol . J. Immunol. , 111 , 1219 – 1227 ( 1973. ). [PubMed] [Google Scholar]
  • 23. ) Lurhuma , A. Z. , Cambiaso , C. L. , Masson , P. L. and Heremans , J. F.Detection of circulating antigen‐antibody complexes by their inhibitory effect on the agglutination of IgG coated latex particles by rheumatoid factor or Clq . Clin. Exp. Immunol , 25 , 212 – 226 ( 1976. ). [PMC free article] [PubMed] [Google Scholar]
  • 24. ) Eisenberg , R.The specificity and polyvalency of binding of a monoclonal rheumatoid factor . Immunochemistry , 13 , 355 – 360 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Theofilopoulos A. N. and Dixon F. J. ( ed. ). Detection of immune complexes; techniques and implications . In “ The Biology of Immunologic Disease ,” pp. 309 – 318 ( 1983. ). Churchill Livingstone Publications; , London . [Google Scholar]
  • 26. ) Poskitt , P. K. F. and Poskitt , T. R.The L1210 assay for immune complexes. Application in cancer patients and correlation with disease progress . Int. J. Cancer , 24 , 560 – 566 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Lambert , P. H. , Dixon , F. J. , Zuber , R. M. , Agnello , V. , Cambiaso , C. , Casali , P. , Clarke , J. , Cowdery , J. S. , McDuffe , F. C. , Hay , F. C. , MacLennan , I. C. M. , Masson , P. , Muller‐Eberhard , H. H. , Penttinen , K. , Smith , M. , Tappeinen , G. , Theofilopoulos , A. N. and Verroust , P.A W.H.O. collaborative study for the evaluation of eighteen methods for detecting immune‐complexes in serum . J. Clin. Immunol. , 1 , 1 – 15 ( 1978. ). [Google Scholar]
  • 28. ) Coons , A. and Kaplan , M. I.Localization of antigen in tissue cells. II. Improvement in a method for detection of antigen by means of fluorescent antibody . J. Exp. Med. , 91 , 1 – 5 ( 1950. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. ) Riggs , J. , Seiwald , R. and Burchhalter , J.Isothiocynate compounds as fluorescent labelling agents for immune serum . Am. J. Pathol , 34 , 1081 – 1085 ( 1958. ). [PMC free article] [PubMed] [Google Scholar]
  • 30. ) Kawapinski G. ( ed. ). The immunofluorescence assay . In “ The Methodology of Investigative and Clinical Immunology ,” pp. 245 – 258 ( 1982. ). Robert E.Kreiger Publication; , Florida . [Google Scholar]
  • 31. ) Mackel , S. E. , Tappeiner , G. , Brumfleld , H. and Jordan , R. E.Circulating immune complexes in cutaneous vasculitis. Detection with C1q and monoclonal rheumatoid factor . J. Clin. Invest , 64 , 1652 – 1660 ( 1979. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES