Immunoarchitecture of lymphoid tissue in HIV-infection during antiretroviral therapy correlates with viral persistence

Alós, Llúcia; Navarrete, Pilar; Morente, Vanesa; García, Felipe; Garrido, M; Plana, Montse; Mozos, Anna; Lopez, Anna Lena; Gil, Cristina; Pumarola, Tomás; Caballero, Miguel; Blanch, José Luís; Fumero, Emilio; Miró, José M.; Gallart, Teresa; Gatell, José M.; Campo, Elı́as

doi:10.1038/modpathol.3800267

Cited by 45 publications

(34 citation statements)

References 33 publications

(52 reference statements)

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“…In agreement with results of other studies [11,26,27], the follicular dendritic cell network recovered after therapy, as shown by a significant increase in CD21. In most of our patients, however, the follicular dendritic cell network was not completely disrupted prior to therapy, presumably because the patients were still in an early stage of HIV infection.…”

Section: Discussionsupporting

confidence: 92%

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Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

et al. 2008

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Background: CD4+ T cell depletion and destruction and the involution of the lymphoid tissue are hallmarks of HIV infection. Although the underlying mechanisms are still unclear, apoptosis appears to play a central role. The objective of this study was to investigate the effect of antiretroviral therapy on the lymph node tissue, particularly with respect to morphology and apoptosis. Patients and Methods: Between 1997 and 1999, two inguinal lymph nodes were excised from 31 previously untreated individuals who were in an early stage of HIV infection, the first one prior to treatment and the second after 16 to 20 months of treatment. Paraffin sections were investigated for lymph node architecture, distribution of cellular and viral markers, apoptosis, and expression of apoptotic key molecules which indirectly reflect apoptotic processes.

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Section: Discussionsupporting

confidence: 92%

“…We found a high number of CD8+ T cells in the interfollicular area and within the germinal centers before treatment, followed by a significant decrease after treatment. Consistent with other studies [27,29,30], the CD4+ T cell numbers in the lymph nodes increased significantly after therapy.…”

Section: Discussionsupporting

confidence: 91%

Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

et al. 2008

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“…As expected, the results of the investigations for other oncogenic viruses, such as HHV-8 and EBV, were also negative. HIV p24 is a monoclonal antibody that recognizes the viral p24 core antigen and is expressed in tissues where HIV is stored [22]. None of the tumours included in the study showed positivity for this antibody.…”

Section: Discussionmentioning

confidence: 99%

Laryngeal squamous cell carcinoma in HIV‐positive patients: lack of association with human papillomavirus infection

Moyano¹,

Ordi²,

Caballero³

et al. 2009

HIV Medicine

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ObjectivesNeoplasms associated with human papillomavirus (HPV) infection occur at increased frequency in patients with HIV infection/AIDS. Although laryngeal squamous cell carcinomas (LSCCs) in HIVpositive patients are uncommon, a higher incidence of this malignancy in HIV-positive patients than in the general population has been reported. As a proportion of LSCCs are associated with HPV in the general population, the clinicopathological features of a series of LSCCs developing in HIV-positive patients were evaluated to investigate the possible relationship with HPV infection, and infection with other oncogenic viruses. MethodsAll HIV-positive patients with LSCC diagnosed at a single institution from 1998 to 2007 were retrospectively evaluated. The clinicopathological features were analysed and tissues were tested by polymerase chain reaction (PCR), using the short PCR fragment 10 (SPF10) primer, a highly sensitive method for HPV DNA detection. Immunohistochemical studies for HIV p24, p16INK4a and p53 were performed. Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8) were also investigated. ResultsSix out of 4987 HIV-infected patients seen in this period in the Infectious Diseases Department developed LSCC (median age 41.5 years; male to female ratio 1:1). All patients were heavy smokers and the tumours presented at an advanced clinical stage. HPV was not detected in any tumour, not even in two patients with coexisting HPV-associated gynaecological neoplasm. Staining for HIV p24 and p16INK4a was negative, whereas p53 was positive in half the cases. EBV and HHV-8 were also negative. ConclusionLSCC developing in HIV-positive patients is an infrequent neoplasm, not usually associated with HPV infection. It develops in young, heavy smokers and presents at an advanced clinical stage. Laryngeal squamous cell carcinoma (LSCC) in HIVinfected patients is uncommon. Nevertheless, it has been reported that HIV-positive patients have a higher incidence of this malignancy than the general population [4,7]. Interestingly, LSCC has been shown to be associated with HPV in 19-24% of cases in the general population [8,9]. Therefore, a close association between LSCC arising in HIVpositive patients and HPV infection could be hypothesized. In the present study we focused on the clinicopathological features of LSCCs developing in HIV-positive patients, and for the first time the possible association of these tumours with HPV infection was investigated using highly sensitive molecular methods. Moreover, other oncogenic viruses, including Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8), were also investigated. Patients and methods PatientsAll HIV-positive patients with LSCC seen in the Infectious Diseases Department of the Hospital Clinic, University of Barcelona between January 1998 and December 2007 were included in the study. During this period, 4987 HIVpositive patients were evaluated. Demographic data were obtained from the medical records. Tumour site and stage were determined from review of the surgical, radiolog...

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“…20,26 Furthermore, several investigators have shown that HIV antigens get trapped within the follicular dendritic cell network of the lymph node and can remain there in the absence of viral replication. [27][28][29] Thus, even when an individual is on therapy, infected cells are capable of producing gp120 that can be shed, bind to extracellular matrix proteins, and enter the peripheral circulation.…”

Section: 21-23mentioning

confidence: 99%

Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines

Rychert

Strick

Bazner

et al. 2010

AIDS Research and Human Retroviruses

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Events that occur during acute HIV infection likely contribute to the immune dysfunction common in HIVinfected individuals. During this early stage, there is high-level viral replication, loss in CD4 þ T cell number and function, and an up-regulation of proinflammatory and immunoregulatory cytokines. The mechanisms responsible for this are not completely understood. We hypothesize that the HIV envelope glycoprotein, gp120, contributes to immune dysfunction during early HIV infection. Using a cohort of subjects enrolled during acute and early HIV infection, we determined the amount of gp120, TNF-a, IL-6, IL-10, IFN-a, and IFN-g in plasma at baseline and 6 months. At matched time points, we also measured CD4 þ T cell proliferation, T cell activation, and apoptosis. Plasma from 109 subjects was screened for gp120. Thirty-six subjects (33%) had detectable gp120 (0.5-15.6 ng/ml). Subjects with greater than 1 ng/ml of gp120 at baseline had similar levels at all time points tested, even when viral replication was undetectable due to therapy. Subjects with detectable gp120 had higher levels of plasma IL-6, IL-10, and TNF-a. There was no difference in the level of T cell activation, proliferation, or apoptosis in subjects with gp120 compared to those without. We conclude that persistent expression of gp120 occurs in a subset of individuals. Furthermore, the presence of gp120 is associated with higher levels of plasma IL-6, IL-10, and TNF-a, which may contribute to immune dysfunction during early HIV infection.

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Immunoarchitecture of lymphoid tissue in HIV-infection during antiretroviral therapy correlates with viral persistence

Cited by 45 publications

References 33 publications

Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

Laryngeal squamous cell carcinoma in HIV‐positive patients: lack of association with human papillomavirus infection

Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines

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