Summary
In order to investigate the role played by zidovudine (ZDV) as immune modulator, particularly on B-cell response, the anti-V3 loop spectrotype in 115 sera from 26 HIV-infected individuals was evaluated, prior to and during treatment with ZDV, by isoelectric focusing and reverse blotting (IEF-RB), a technique useful for indirectly measuring the activity and the number of B-cell clones. All 18 patients showing seroreactivity by IEFRB displayed a clear oligoclonal banding pattern, with no change in the spectrotype (i.e. new bands), in sequential analysis over the course of therapy. Only minor changes in band intensity were found, without any correlation with ZDV treatment or CD4+ cell count. In addition, among the sera reactive in spectrotypic analysis, the percentage of those with p24 antigen positivity was significantly lower than those with no detectable p24 antigen (19.8% vs 80.2%, respectively, p=<0.0001, Fisher's exact test). In conclusion, it could not be demonstrated by IEFRB that there was any effect of ZDV on the activity and the number of anti-V3 specific B-cell clones. This data is in line with previous studies showing the constancy of anti-gp120 antibody spectrotype over the long course of the disease.
Zusammenfassung
Der Anti-V3-Loop-Spektrotyp wurden in 115 Seren von 26 HIV-Infizierten vor und nach Zidovudin-Therapie bestimmt, um die Rolle von Zidovudin als Immunmodulator, vor allem der B-Zell-Antwort, zu prüfen. Als Methoden wurden isoelektrische Fokussierung und reverses Blotting (IEFRB) eingesetzt, die sich für die indirekte Bestimmung der Aktivität und der Zahl der B-Zell-Klone als brauchbar erwiesen haben. Bei allen 18 seroreaktiven Patienten stellten sich eindeutige oligoklonale Bandenmuster dar. In Verlaufsanalysen während der Therapie war keine Änderung im Spektrotyp, d. h. keine neuen Banden, zu erkennen. Die Bandenintensität änderte sich nur wenig, wobei keine Beziehung zur Zidovudin-Therapie oder den CD4+ Zellzahlen bestand. In den Spektrotyp-positiven Seren war nur bei einem kleinen Anteil auch p24-Antigen nachzuweisen (19,8% positive gegen 80,2% p-24-Antigen negative Seren; p≤0,0001, Fisher's exakter Test). Zusammenfassend fand sich mit IEFRB kein Einfluß von Zidovudin auf die Aktivität und die Zahl anti-V3-spezifischer B-Zell-Klone. Dies stimmt mit den Ergebnissen früherer Studien überein, in denen Konstanz des anti-gp120-Antikörper-Spektrotyps im Langzeitverlauf der Erkrankung festgestellt wurde.
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Mitsuya, H., Veinhold, K. J., Furman, P. A., St. Clair, M. H., Lehrman, S. N., Gallo, R. C., Bolognesi, D., Barry, D. W., Broder, S. 3-azido 3 deoxythymidine (BW A509U): an antiviral agent that inhibits infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphoadenopathy-associated virusin vitro. Proc. Natl. Acad. Sci. USA 85 (1985) 7096–7100.
Fischl, M. A., Richman, D. D., Grieco, M. H., andthe AIDS Clinical Trial Group The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N. Engl. J. Med. 317 (1987) 185–191.
Yarchoan, R., Klecker, R. W., Weinhold, K. J., Markham, P. D., Lyerly, H. K., Durack, D. T., Gelmann, E., Lehrman, S. N., Blum, R. M., Barry, D. W. Administration of 3′-azido-3′deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet i (1986) 575–580.
Volberding, P. A., Lagakos, S. W., Koch, M. A., andthe AIDS Clinical Trial Group Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS clinical trials groups of the National Institute of Allergy and Infectious Diseases. N. Engl. J. Med. 322 (1990) 941–949.
Gerding, M. N., Schwurman, H. J., Bast, B. J. E. G., Borleffs, J. C. C. Lymphocytes intrinsic lymphoproliferative capacity in patients with AIDS treated with zidovudine. AIDS 3 (1989) 671–673.
Rinaldo, C., Huang, X. L., Piazza, P., Armstrong, J., Rappocciolo, G., Pazin, G., McMahon, D., Gupta, P., Fan, Z., Zhang, Z., Ho, M. Augmentation of cellular immune function during the early phase of zidovudine treatment of AIDS patients. J. Infect. Dis. 164 (1991) 638–645.
Clerici, M., Landay, A. L., Kessler, H. A., Phair, J. P., Venzon, D. J., Hendrix, C. W., Lucey, D. R., Shearer, G. M. Reconstitution of long-term T helper cell function after zidovudine therapy in human immunodeficiency virus-infected patients. J. Infect. Dis. 166 (1992) 723–730.
Zamarchi, R., Panozzo, M., Del Mistro, A., Barelli, A., Borri, A., Amadori, A., Chieco-Bianchi, L. B and T cell function parameters during zidovudine treatment of human immunodeficiency virus-infected patients. J. Infect. Dis. 170 (1994) 1148–1156.
Rusche, J. R., Javaherian, K., McDanal, C., Petro, J., Lynn, D. L., Grimaila, R., Langlois, A., Gallo, R. C., Arthur, L. O., Fischinger, P. J., Bolognesi, D. P., Putney, S. D., Matthews, T. J. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc. Natl. Acad. Sci. USA 85 (1988) 3198–3202.
Askonas, B., Williamson, A. R., Wright, B. E. G. Selection of a single antibody-forming cell clone and its propagation in syngeneic mice. Proc. Natl. Acad. Sci. USA 67 (1970) 1398–1401.
Roos, R. P., Nalefski, E. A., Nitayaphan, S., Variakojis, R., Singh, K. K. An isoelectric focusing overlay study of the humoral immune response in Theiler's virus demyelinating disease. J. Neuroimmunol. 13 (1987) 305–314.
Grimaldi, L. M. E., Roos, R. P., Devare, S. G., Robey, W. G., Robey, J. M., Robey, M. E., Apatoff, B. R. Lazzarin, A. Restricted heterogeneity of antibody to gp120 and p24 in AIDS. J. Immunol. 141 (1988) 114–117.
D'Amelio, R. Biselli, R., Nisini, R., Matricardi, P. M., Aiuti, A., Mezzaroma, I., Pinter, E., Pontesilli, O., Aiuti, F. Spectrotype of anti-gp120 antibodies remains stable during the course of HIV disease. J. Acquir. Immune Defic. Syndr. 5 (1992) 930–935.
Redfield, R. R., Birx, D. L., Ketter, N., Tramont, E., Polonis, V., Davis, C., Brundage, J. F., Smith, G., Johnson, S., Fowler, A., Wierzba, T., Shafferman, A., Volvovitz, F., Oster, C., Burke, D. S. andthe Military Medical Consortium for Applied Retroviral Research A Phase 1 evaluation of the safety and immunogenicity of vaccination with recombinant gp 160 in patients with early human immunodeficiency virus infection. N. Engl. J. Med. 324 (1991) 1677–1684.
Biselli, R., Loomis, L. D., Del Bono, V., Burke, D. S., Redfield, R. R., Birx, D. L. Immunization of HIV-infected patients with rgp 160: modulation of anti-rgp 120 antibody spectrotype. J. Acquir. Immune Defic. Syndr. 7 (1994) 1016–1024.
Cao, Y., Ho, D. D., Todd, J., Kokka, R., Urdea, M., Lifson, J. D., Piatak, M., JR, Chen, S., Hahn, B. H., Saag, M. S., Shaw, G. M. Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma. AIDS Res. Hum. Retroviruses 11 (1995) 353–361.
Eron, J., Benoit, S., Jemsek, J., Quinn, J., Fallon, M. A., Rubin, M.: A randomized double-blind multicenter comparative trial of lamivudine (3TC) monotherapy vs. zidovudine (ZDV) monotherapy vs. 3TC + ZDV combination in native patients with CD4+ cell counts of 200–500/mm3. Second National Conference on Human Retroviruses and Related Infections, Washington, D.C., 1995, abstr. 173.
Zimmermann, F., Biesert, L., von Briesen, H., Vegner, R., Helm, E. B., Staszewski, S., Rubsamen-Waigmann, H.: Development of HIV-variants with higher resistance against AZT under treatment with AZT. IV. International Conference on AIDS, Stockholm, 1988, abstr. 3656.
Larder, B. A., Darby, G., Richman, D. D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243 (1989) 1731–1734.
Baur, A., Vornhagen, R., Korn, K., Sonneborn, H. H., Eberlein, B., Harrer, T., Brockhaus, W., Hahn, G. Viral culture and P24 antigenemia of human immunodeficiency virus (HIV)-infected individuals correlated with antibody profiles determined with recombinant polypeptides of all HIV-1 open-reading frames. J. Infect. Dis. 165 (1992) 419–426.
Amadori, A., De Silvestro, G., Zamarchi, R., Veronese, M. L., Mazza, M. R., Schiavo, G., Panozzo, M., De Rossi, A., Ometto, L., Mous, J., Barelli, A., Borri, A., Salmaso, L., Chieco-Bianchi, L. CD4 epitope masking by gp120/anti-gp120 antibody complexes. A potential mechanism for CD4+ cell function down-regulation in AIDS patients. J. Immunol. 148 (1992) 2709–2716.
Bagnarelli, P., Menzo, S., Manzin, A., Giacca, M., Varaldo, P. E., Clementi, M. Detection of human immunodeficiency virus type 1 genomic RNA in plasma samples by reverse-transcription polymerase chain reaction. J. Virol. Methods 34 (1991) 89–95.
Pachl, C., Todd, J. A., Kern, D. G., Sheridan, P. J., Fong, S., Stempien, M., Hoo, B., Besemer, D., Yeghiazarian, T., Irvine, B., Kolberg, J., Kokka, R., Neuwald, P., Urdea, M. S. Rapid and precise quantification of HIV-1 RNA in plasma using a branched DNA signal amplification assay. AIDS 8 (1995) 446–454.
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Biselli, R., D'Amelio, R., Del Bono, V. et al. Anti-V3 loop spectrotype in HIV-infected individuals during zidovudine therapy. Infection 24, 227–233 (1996). https://doi.org/10.1007/BF01781097
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DOI: https://doi.org/10.1007/BF01781097