Abstract
Whether HAART allows complete recovery of humoral immune function in HIV-infected individuals is still controversial. Our objective was to study the effect of HAART on both B cell repopulation and hypergammaglobulinemia in 72 naïve patients, including 35 HCV-coinfected individuals, during 156 weeks on HAART. The possible role of HCV coinfection on the recovery of the humoral immune system was also investigated. At baseline, HCV-coinfected patients had greater circulant IgG levels than HIV-only-infected patients, while B cell count and CD21low B cell subpopulation were similar in both groups. During HAART, HIV-only-infected patients reached normal B cell counts and circulant IgG levels, while HCV-coinfected individuals did not. CD21low B cell subpopulation significantly decreased in both groups of patients at week 48 after the initiation of HAART compared to baseline. Thus, B cells remained continuously stimulated in HCV-coinfected patients and this stimulation seemed to be through a CD21-independent pathway.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Reddy MM, Goetz RR, Gorman JM, Grieco MH, Chess L, Lederman S: Human Immunodeficiency virus type-1 infection of homosexual men is accompanied by a decrease in circulating B cells. J Acquir Immune Defic Syndr 4:428–434, 1991
Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS: Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 309:453–458, 1983
Nagase H, Agematsu K, Kitano K, Takamoto M, Okubo Y, Komiyama A, Sugane K: Mechanism of hypergammaglobulinemia by HIV infection: Circulating memory B-cell reduction with plasmacytosis. Clin Immunol 100:250–259, 2001
Hunziker L, Recher M, Macpherson AJ, Ciurea A, Freigang S, Hengartner H, Zinkernagel RM: Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections. Nat Immunol 4:343–349, 2003
De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, Grutzmeier S, Sonnerborg A, Chiodi F: Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood 103:2180–2186, 2004
Morris L, Binley JM, Clas BA, Bonhoeffer S, Astill TP, Kost R, Hurley A, Cao Y, Markowitz M, Ho DD, Moore JP: HIV-1 antigen-specific and -nonspecific B cell responses are sensitive to combination antiretroviral therapy. J Exp Med 188:233–245, 1998
Notermans DW, de Jong JJ, Goudsmit J, Bakker M, Roos MT, Nijholt L, Cremers J, Hellings JA, Danner SA, de Ronde A: Potent antiretroviral therapy initiates normalization of hypergammaglobulinemia and a decline in HIV type 1-specific antibody responses. AIDS Res Hum Retroviruses 17:1003–1008, 2001
Yokozaki S, Takamatsu J, Nakano I, Katano Y, Toyoda H, Hayashi K, Hayakawa T, Fukuda Y: Immunologic dynamics in hemophiliac patients infected with hepatitis C virus and human immunodeficiency virus: Influence of antiretroviral therapy. Blood 96:4293–4299, 2000
Jacobson MA, Khayam-Bashi H, Martin JN, Martin JN, Black D, Ng V: Effect of long-term highly active antiretroviral therapy in restoring HIV-induced abnormal B-lymphocyte function. J Acquir Immune Defic Syndr 31:472–477, 2002
Zehender G, Meroni L, De Maddalena C, Varchetta S, Monti G, Galli M: Detection of hepatitis C virus RNA in CD19 peripheral blood mononuclear cells of chronically infected patients. J Infect Dis 176:1209–1214, 1997
Morsica G, Tambussi G, Sitia G, Novati R, Lazzarin A, Lopalco L, Mukenge S, Agnello V, Chung RT, Kaplan LM: Replication of hepatitis C virus in B lymphocytes (CD19+). Blood 94:1138–1139, 1999
Agnello V, Chung RT, Kaplan LM: A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 327:1490–1495, 1992
Ferri C, Monti M, La Civita L, Longombardo G, Greco F, Pasero G, Gentilini P, Bombardieri S, Zignego AL: Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed cryoglobulinemia. Blood 82:3701–3704, 1993
Zignego AL, Brechot C: Extrahepatic manifestations of HCV infection: Facts and controversies. J Hepatol 31:369–376, 1999
Franco JM, Rubio A, Martinez-Moya M, Leal M, Merchante E, Sanchez-Quijano A, Lissen E: T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy. Blood 99:3702–3706, 2002
Sung VM, Shimodaira S, Doughty AL, Picchio GR, Can H, Yen TS, Lindsay KL, Levine AM, Lai MM: Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection. J Virol 77:2134–2146, 2003
Slifka MK, Ahmed R: Long-term antibody production is sustained by antibody-secreting cells in the bone marrow following acute viral infection. Ann NY Acad Sci 797:166–176, 1996
Bender BS, Frank MM, Lawley TJ, Smith WJ, Brickman CM, Quinn TC: Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. J Infect Dis 152: 409–412, 1985
Bender BS, Bohnsack JF, Sourlis SH, Frank MM, Quinn TC: Demonstration of defective C3-receptor-mediated clearance by the reticuloendothelial system in patients with acquired immunodeficiency syndrome. J Clin Invest 79:715–720, 1987
Roccatello D, Morsica G, Picciotto G, Cesano G, Ropolo R, Bernardi MT, Cacace G, Cavalli G, Sena LM, Lazzarin A, Piccoli G, Rifai A: Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection. Clin Exp Immunol 110:9–14, 1997
Watt K, Uhanova J, Gong Y, Kaita K, Doucette K, Pettigrew N, Minuk GY: Serum immunoglobulins predict the extent of hepatic fibrosis in patients with chronic hepatitis C virus infection. J Viral Hepat 11:251–256, 2004
Gonzalez-Quintela A, Alende MR, Gamallo R, Gonzalez-Gil P, Lopez-Ben S, Tome S, Otero E, Torre JA: Serum immunoglobulins (IgG, IgA, IgM) in chronic hepatitis C. A comparison with non-cirrhotic alcoholic liver disease. Hepatogastroenterol 50:2121–2126, 2003
Ginaldi L, De Martinis M, D’Ostilio A, Marini L, Quaglino D: Changes in antigen expression on B lymphocytes during HIV infection. Pathobiology 66:17–23, 1998
Moir S, Malaspina A, Yuexia Li, Chun TW, Lowe T, Adelsberger J, Baseler M, Ehler LA, Liu S, Davey RT Jr, Mican JA, Fauci AS: B cells of HIV-1-infected patients bind virions through CD21-complement interactions and transmit infectious virus to activated T cells. J Exp Med 192:637–646, 2000
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Soriano-Sarabia, N., Leal, M., Delgado, C. et al. Effect of Hepatitis C Virus Coinfection on Humoral Immune Alterations in Naïve HIV-Infected Adults on HAART: A Three Year Follow-Up Study. J Clin Immunol 25, 296–302 (2005). https://doi.org/10.1007/s10875-005-3864-1
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10875-005-3864-1