Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Jan;87(1):24–30. doi: 10.1111/j.1365-2249.1992.tb06408.x

Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection.

R J Klaassen 1, R Goldschmeding 1, K M Dolman 1, A B Vlekke 1, H M Weigel 1, J K Eeftinck Schattenkerk 1, J W Mulder 1, M L Westedt 1, A E von dem Borne 1
PMCID: PMC1554226  PMID: 1733634

Abstract

Antibodies against cytoplasmic antigens of neutrophils, producing perinuclear (p-ANCA) as well as cytoplasmic staining with central accentuation (c-ANCA), have been described in non-HIV-infected patients with specific pathology such as glomerulonephritis and vasculitis. Here, we report on a patient with a vasculitis-like syndrome and a positive ANCA-test who appeared to be infected by HIV. Further analysis revealed that ANCA, p-ANCA as well as c-ANCA without central accentuation can be demonstrated in the serum of HIV+ individuals. In a cross-sectional study on individuals in different stages of HIV infection, we found that the occurrence of ANCA was limited to the symptomatic stages of HIV infection: p-ANCA was found in one out of 10 ARC patients and in two out of 11 AIDS patients with malignancies (AIDS-MAL), but not in AIDS patients with opportunistic infections (AIDS-OI). c-ANCA was found in four of the ARC patients, in two of the 14 AIDS-OI patients and in two AIDS-MAL patients. The presence of ANCA was not related to the degree of hypergammaglobulinaemia nor to specific symptomatology. ANCA containing sera from HIV+ individuals did not react with HEp2 cells nor with cytoplasmic antigens of lymphocytes, natural killer (NK) cells or eosinophils. Five out of the 11 (two p-ANCA and three c-ANCA) sera reacted weakly with cytoplasmic antigens of monocytes. All sera reacted with karyoplasts but not with cytoplasts prepared from neutrophils. These results suggest that HIV-ANCA might be directed against myeloid cell-specific granule constituents. However, sandwich-ELISAs with MoAbs against granule antigens that are frequently the target antigens of ANCA in HIV- individuals were negative. Also immunoprecipitation and immunoblotting, using lysates of neutrophil granules, did not allow further identification of the target antigens of HIV-ANCA.

Full text

PDF
24

Images in this article

28Fig. 2
on p.28

Selected References

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

  1. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  2. Bom-van Noorloos A. A., Pegels H. G., van Oers R. H., Silberbusch J., Feltkamp-Vroom T. M., Goudsmit R., Zeijlemaker W. P., von dem Borne A. E., Melief C. J. Proliferation of T gamma cells with killer-cell activity in two patients with neutropenia and recurrent infections. N Engl J Med. 1980 Apr 24;302(17):933–937. doi: 10.1056/NEJM198004243021702. [DOI] [PubMed] [Google Scholar]
  3. Boot J. H., Geerts M. E., Aarden L. A. Functional polymorphisms of Fc receptors in human monocyte-mediated cytotoxicity towards erythrocytes induced by murine isotype switch variants. J Immunol. 1989 Feb 15;142(4):1217–1223. [PubMed] [Google Scholar]
  4. Borregaard N., Heiple J. M., Simons E. R., Clark R. A. Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation. J Cell Biol. 1983 Jul;97(1):52–61. doi: 10.1083/jcb.97.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bowen D. L., Lane H. C., Fauci A. S. Immunopathogenesis of the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):704–709. doi: 10.7326/0003-4819-103-5-704. [DOI] [PubMed] [Google Scholar]
  6. Davies D. J., Moran J. E., Niall J. F., Ryan G. B. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? 1982 Aug 28-Sep 4Br Med J (Clin Res Ed) 285(6342):606–606. doi: 10.1136/bmj.285.6342.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Edelman A. S., Zolla-Pazner S. AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency. FASEB J. 1989 Jan;3(1):22–30. doi: 10.1096/fasebj.3.1.2562947. [DOI] [PubMed] [Google Scholar]
  8. Falk R. J., Jennette J. C. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988 Jun 23;318(25):1651–1657. doi: 10.1056/NEJM198806233182504. [DOI] [PubMed] [Google Scholar]
  9. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  10. Gardenswartz M. H., Lerner C. W., Seligson G. R., Zabetakis P. M., Rotterdam H., Tapper M. L., Michelis M. F., Bruno M. S. Renal disease in patients with AIDS: a clinicopathologic study. Clin Nephrol. 1984 Apr;21(4):197–204. [PubMed] [Google Scholar]
  11. Goldschmeding R., Tervaert J. W., Gans R. O., Dolman K. M., van den Ende M. E., Kuizinga M. C., Kallenberg C. G., von dem Borne A. E. Different immunological specificities and disease associations of c-ANCA and p-ANCA. Neth J Med. 1990 Apr;36(3-4):114–116. [PubMed] [Google Scholar]
  12. Goldschmeding R., van der Schoot C. E., ten Bokkel Huinink D., Hack C. E., van den Ende M. E., Kallenberg C. G., von dem Borne A. E. Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils. J Clin Invest. 1989 Nov;84(5):1577–1587. doi: 10.1172/JCI114335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ho D. D., Rota T. R., Hirsch M. S. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest. 1986 May;77(5):1712–1715. doi: 10.1172/JCI112491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  15. Koderisch J., Andrassy K., Rasmussen N., Hartmann M., Tilgen W. "False-positive" anti-neutrophil cytoplasmic antibodies in HIV infection. Lancet. 1990 May 19;335(8699):1227–1228. doi: 10.1016/0140-6736(90)92755-7. [DOI] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Lane H. C., Depper J. M., Greene W. C., Whalen G., Waldmann T. A., Fauci A. S. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. N Engl J Med. 1985 Jul 11;313(2):79–84. doi: 10.1056/NEJM198507113130204. [DOI] [PubMed] [Google Scholar]
  18. Lüdemann G., Gross W. L. Autoantibodies against cytoplasmic structures of neutrophil granulocytes in Wegener's granulomatosis. Clin Exp Immunol. 1987 Aug;69(2):350–357. [PMC free article] [PubMed] [Google Scholar]
  19. Murphy M. F., Metcalfe P., Waters A. H., Carne C. A., Weller I. V., Linch D. C., Smith A. Incidence and mechanism of neutropenia and thrombocytopenia in patients with human immunodeficiency virus infection. Br J Haematol. 1987 Jul;66(3):337–340. doi: 10.1111/j.1365-2141.1987.tb06920.x. [DOI] [PubMed] [Google Scholar]
  20. Pinching A. J., Rees A. J., Pussell B. A., Lockwood C. M., Mitchison R. S., Peters D. K. Relapses in Wegener's granulomatosis: the role of infection. Br Med J. 1980 Sep 27;281(6244):836–838. doi: 10.1136/bmj.281.6244.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pulford K. A., Erber W. N., Crick J. A., Olsson I., Micklem K. J., Gatter K. C., Mason D. Y. Use of monoclonal antibody against human neutrophil elastase in normal and leukaemic myeloid cells. J Clin Pathol. 1988 Aug;41(8):853–860. doi: 10.1136/jcp.41.8.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rao T. K., Friedman E. A., Nicastri A. D. The types of renal disease in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Apr 23;316(17):1062–1068. doi: 10.1056/NEJM198704233161705. [DOI] [PubMed] [Google Scholar]
  23. Roos D., Voetman A. A., Meerhof L. J. Functional activity of enucleated human polymorphonuclear leukocytes. J Cell Biol. 1983 Aug;97(2):368–377. doi: 10.1083/jcb.97.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Roos D., de Boer M. Purification and cryopreservation of phagocytes from human blood. Methods Enzymol. 1986;132:225–243. doi: 10.1016/s0076-6879(86)32010-x. [DOI] [PubMed] [Google Scholar]
  25. Savage C. O., Winearls C. G., Jones S., Marshall P. D., Lockwood C. M. Prospective study of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet. 1987 Jun 20;1(8547):1389–1393. doi: 10.1016/s0140-6736(87)90591-5. [DOI] [PubMed] [Google Scholar]
  26. Stroncek D. F., Skubitz K. M., McCullough J. J. Biochemical characterization of the neutrophil-specific antigen NB1. Blood. 1990 Feb 1;75(3):744–755. [PubMed] [Google Scholar]
  27. Tervaert J. W., Goldschmeding R., Elema J. D., Limburg P. C., van der Giessen M., Huitema M. G., Koolen M. I., Hené R. J., The T. H., van der Hem G. K. Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum. 1990 Aug;33(8):1264–1272. doi: 10.1002/art.1780330829. [DOI] [PubMed] [Google Scholar]
  28. Tervaert J. W., Goldschmeding R., Elema J. D., van der Giessen M., Huitema M. G., van der Hem G. K., The T. H., von dem Borne A. E., Kallenberg C. G. Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. Kidney Int. 1990 Feb;37(2):799–806. doi: 10.1038/ki.1990.48. [DOI] [PubMed] [Google Scholar]
  29. Tervaert J. W., Huitema M. G., Hené R. J., Sluiter W. J., The T. H., van der Hem G. K., Kallenberg C. G. Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet. 1990 Sep 22;336(8717):709–711. doi: 10.1016/0140-6736(90)92205-v. [DOI] [PubMed] [Google Scholar]
  30. Tervaert J. W., van der Woude F. J., Fauci A. S., Ambrus J. L., Velosa J., Keane W. F., Meijer S., van der Giessen M., van der Hem G. K., The T. H. Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989 Nov;149(11):2461–2465. doi: 10.1001/archinte.149.11.2461. [DOI] [PubMed] [Google Scholar]
  31. Verheugt F. W., von dem Borne A. E., van Noord-Bokhorst J. C., Engelfriet C. P. Autoimmune granulocytopenia: the detection of granulocyte autoantibodies with the immunofluorescence test. Br J Haematol. 1978 Jul;39(3):339–350. doi: 10.1111/j.1365-2141.1978.tb01106.x. [DOI] [PubMed] [Google Scholar]
  32. Ziegler J. L., Stites D. P. Hypothesis: AIDS is an autoimmune disease directed at the immune system and triggered by a lymphotropic retrovirus. Clin Immunol Immunopathol. 1986 Dec;41(3):305–313. doi: 10.1016/0090-1229(86)90001-2. [DOI] [PubMed] [Google Scholar]
  33. de Wolf F., Goudsmit J., Paul D. A., Lange J. M., Hooijkaas C., Schellekens P., Coutinho R. A., van der Noordaa J. Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia. Br Med J (Clin Res Ed) 1987 Sep 5;295(6598):569–572. doi: 10.1136/bmj.295.6598.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. van der Lelie J., Lange J. M., Vos J. J., van Dalen C. M., Danner S. A., von dem Borne A. E. Autoimmunity against blood cells in human immunodeficiency-virus (HIV) infection. Br J Haematol. 1987 Sep;67(1):109–114. doi: 10.1111/j.1365-2141.1987.tb02304.x. [DOI] [PubMed] [Google Scholar]
  35. van der Schoot C. E., von dem Borne A. E., Tetteroo P. A. Characterization of myeloid leukemia by monoclonal antibodies, with an emphasis on antibodies against myeloperoxidase. Acta Haematol. 1987;78 (Suppl 1):32–40. doi: 10.1159/000205900. [DOI] [PubMed] [Google Scholar]
  36. van der Woude F. J., Rasmussen N., Lobatto S., Wiik A., Permin H., van Es L. A., van der Giessen M., van der Hem G. K., The T. H. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet. 1985 Feb 23;1(8426):425–429. doi: 10.1016/s0140-6736(85)91147-x. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES