Abstract
The humoral immune response to four intracellularly located cytomegalovirus (CMV) proteins was studied in 15 lung transplant recipients experiencing active CMV infections. Five patients had primary infections, and 10 had secondary infections. Antibodies of the immunoglobulin M (IgM) and IgG classes were measured in an enzyme-linked immunosorbent assay (ELISA) system in which procaryotically expressed recombinant proteins were used as a substrate and also in a monoclonal antibody-based capture ELISA which uses naturally occurring proteins as a substrate. The proteins investigated were the lower matrix protein pp65 (ppUL83), the major DNA-binding protein p52 (ppUL44), and the two immediate early proteins IE1 and IE2 (different splicing products of UL123). Higher levels of antibodies were found to pp65 and especially to p52 than to the immediate early antigens. Antibody levels detected in the recombinant protein-based ELISAs were generally lower than antibody responses detected with the matching antigen capture ELISA. Moreover, some patients appeared to have antibodies mainly to epitopes present on naturally occurring proteins. The antibody responses detected in both assays were related to the viral load during infection as assessed by the CMV antigenemia test, which is a quantitative marker for CMV load. It was found that although epitopes on naturally occurring proteins induce higher antibody responses and responses in more patients, antibodies directed to epitopes present on the recombinant proteins were inversely related to the viral load during a CMV infection. Therefore, antibodies to epitopes on the recombinant proteins might be more clinically relevant in this group of lung transplant recipients.
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- Borysiewicz L. K., Hickling J. K., Graham S., Sinclair J., Cranage M. P., Smith G. L., Sissons J. G. Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. J Exp Med. 1988 Sep 1;168(3):919–931. doi: 10.1084/jem.168.3.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cremer N. E., Cossen C. K., Shell G. R., Pereira L. Antibody response to cytomegalovirus polypeptides captured by monoclonal antibodies on the solid phase in enzyme immunoassays. J Clin Microbiol. 1985 Apr;21(4):517–521. doi: 10.1128/jcm.21.4.517-521.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gold D., Ashley R., Handsfield H. H., Verdon M., Leach L., Mills J., Drew L., Corey L. Immunoblot analysis of the humoral immune response in primary cytomegalovirus infection. J Infect Dis. 1988 Feb;157(2):319–326. doi: 10.1093/infdis/157.2.319. [DOI] [PubMed] [Google Scholar]
- Grefte J. M., van der Gun B. T., Schmolke S., van der Giessen M., van Son W. J., Plachter B., Jahn G., The T. H. The lower matrix protein pp65 is the principal viral antigen present in peripheral blood leukocytes during an active cytomegalovirus infection. J Gen Virol. 1992 Nov;73(Pt 11):2923–2932. doi: 10.1099/0022-1317-73-11-2923. [DOI] [PubMed] [Google Scholar]
- Gönczöl E., Ianacone J., Furlini G., Ho W., Plotkin S. A. Humoral immune response to cytomegalovirus Towne vaccine strain and to Toledo low-passage strain. J Infect Dis. 1989 May;159(5):851–859. doi: 10.1093/infdis/159.5.851. [DOI] [PubMed] [Google Scholar]
- Jonjić S., del Val M., Keil G. M., Reddehase M. J., Koszinowski U. H. A nonstructural viral protein expressed by a recombinant vaccinia virus protects against lethal cytomegalovirus infection. J Virol. 1988 May;62(5):1653–1658. doi: 10.1128/jvi.62.5.1653-1658.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kropff B., Landini M. P., Mach M. An ELISA using recombinant proteins for the detection of neutralizing antibodies against human cytomegalovirus. J Med Virol. 1993 Mar;39(3):187–195. doi: 10.1002/jmv.1890390303. [DOI] [PubMed] [Google Scholar]
- Landini M. P., Guan M. X., Jahn G., Lindenmaier W., Mach M., Ripalti A., Necker A., Lazzarotto T., Plachter B. Large-scale screening of human sera with cytomegalovirus recombinant antigens. J Clin Microbiol. 1990 Jun;28(6):1375–1379. doi: 10.1128/jcm.28.6.1375-1379.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Landini M. P., Lazzarotto T., Ertl P. F. Humoral immune response to human cytomegalovirus DNA polymerase. J Clin Microbiol. 1993 Mar;31(3):724–726. doi: 10.1128/jcm.31.3.724-726.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Landini M. P., Re M. C., Mirolo G., Baldassarri B., La Placa M. Human immune response to cytomegalovirus structural polypeptides studied by immunoblotting. J Med Virol. 1985 Dec;17(4):303–311. doi: 10.1002/jmv.1890170403. [DOI] [PubMed] [Google Scholar]
- Van der Giessen M., van den Berg A. P., van der Bij W., Postma S., van Son W. J., The T. H. Quantitative measurement of cytomegalovirus-specific IgG and IgM antibodies in relation to cytomegalovirus antigenaemia and disease activity in kidney recipients with an active cytomegalovirus infection. Clin Exp Immunol. 1990 Apr;80(1):56–61. doi: 10.1111/j.1365-2249.1990.tb06441.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van der Voort L. H., Van Zanten J., De Leij L. F., The T. H. Determination of human antibodies to specific antigens of cytomegalovirus using an antigen capture immunoassay. J Immunol Methods. 1989 Jul 6;121(1):95–103. doi: 10.1016/0022-1759(89)90424-9. [DOI] [PubMed] [Google Scholar]
- van Zanten J., van der Giessen M., van Son W. J., The T. H. Antibody responses to human cytomegalovirus-specific polypeptides studied by immunoblotting in relation to viral load during cytomegalovirus infection. J Med Virol. 1993 Jan;39(1):80–87. doi: 10.1002/jmv.1890390115. [DOI] [PubMed] [Google Scholar]
- van den Berg A. P., van der Bij W., van Son W. J., Anema J., van der Giessen M., Schirm J., Tegzess A. M., The T. H. Cytomegalovirus antigenemia as a useful marker of symptomatic cytomegalovirus infection after renal transplantation--a report of 130 consecutive patients. Transplantation. 1989 Dec;48(6):991–995. doi: 10.1097/00007890-198912000-00019. [DOI] [PubMed] [Google Scholar]
- van der Bij W., Torensma R., van Son W. J., Anema J., Schirm J., Tegzess A. M., The T. H. Rapid immunodiagnosis of active cytomegalovirus infection by monoclonal antibody staining of blood leucocytes. J Med Virol. 1988 Jun;25(2):179–188. doi: 10.1002/jmv.1890250208. [DOI] [PubMed] [Google Scholar]