RESUMEN
We hypothesized that HIV-1-mediated T-cell loss might induce the production of factors that are capable of stimulating lymphocyte development and expansion. Here we perform cross-sectional (n = 168) and longitudinal (n = 11) analyses showing that increased circulating levels of interleukin (IL)-7 are strongly associated with CD4+ T lymphopenia in HIV-1 disease. Using immunohistochemistry with quantitative image analysis, we demonstrate that IL-7 is produced by dendritic-like cells within peripheral lymphoid tissues and that IL-7 production by these cells is greatly increased in lymphocyte-depleted tissues. We propose that IL-7 production increases as part of a homeostatic response to T-cell depletion.
Asunto(s)
VIH-1/fisiología , Interleucina-7/biosíntesis , Depleción Linfocítica , Linfocitos T/citología , Estudios de Cohortes , Progresión de la Enfermedad , Infecciones por VIH/patología , Humanos , Inmunohistoquímica , Estudios Longitudinales , Tejido Linfoide/metabolismo , Tejido Linfoide/virologíaRESUMEN
Baboons (Papio cynocephalus) provide a valuable animal model for the study of human immunodeficiency virus (HIV) pathogenesis because HIV-2 infection of baboons causes a chronic viral disease that progresses over several years before clinical signs of acquired immunodeficiency syndrome (AIDS) appear. Since HIV-2-infected baboons develop a chronic viral infection, insights into the immuno-biology of viral latency, clinical stages of disease, virus infection of lymphatic tissue and HIV transmission can be gained using this animal model. The development of an AIDS-like disease in baboons is viral isolate and baboon subspecies dependent. Thus, viral virulence factors and host resistance can be studied as well as the mechanisms of innate and acquired immunity. The control of virus infection is dependent upon cytotoxic and non-cytotoxic antiviral activity of CD8+ T cells. In this regard, some of the HIV-2-infected baboons develop potent antiviral cellular immune responses that have a similar magnitude to that found in HIV-1-infected long-term survivors (or non-progressors). In our laboratory, baboons have been used to study DNA vaccine strategies using new cationic liposome formulations and granulocyte macrophage-colony stimulating factor and B7-2 as genetic adjuvants. The results demonstrate the value of using baboons as an animal model of AIDS pathogenesis and vaccine development.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/microbiología , Infecciones por VIH/inmunología , VIH-2/patogenicidad , Modelos Animales , Papio , Vacunas contra el SIDA/inmunología , Síndrome de Inmunodeficiencia Adquirida/etiología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Animales , Femenino , Infecciones por VIH/etiología , VIH-2/inmunología , Humanos , Inmunidad Innata/inmunología , MasculinoRESUMEN
An essential component of the HIV-1 life cycle involves insertion in the genome of an infected cell. The site of HIV-1 integration has the potential to disrupt a gene and perturb a normal cellular function. To begin to address whether disease pathogenesis may correlate with the site of insertion, flanking cellular sequences at these HIV integrated regions were directly amplified from peripheral blood mononuclear cells DNA from a broad range of infected individuals using an inverse polymerase chain reaction strategy. Amplified flanking regions were sequenced and examined for similarity to the nucleic acid database. In this group of analyzed samples, the HIV-1 provirus was inserted within non-coding regions throughout the genome of the infected host, in which 7/14 sites were positioned in close proximity to different Alu repetitive elements while 2/14 sites were located within intron sequences. Insertions were also detected at sites without a specific gene designation but not within short tandem repetitive sequences, telomeres or centromeric repeat regions. Altogether, it is expected that this approach will yield new information on sites of integration by HIV-1 that may be associated with the pathogenic manifestations of disease progression.
Asunto(s)
Sangre/virología , ADN Viral/análisis , Infecciones por VIH/virología , VIH-1/genética , Linfocitos/virología , Integración Viral , Secuencia de Bases , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 6 , VIH-1/aislamiento & purificación , Humanos , Intrones , Datos de Secuencia Molecular , Provirus/genética , Provirus/aislamiento & purificación , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Human herpesvirus 6 (HHV-6) has been proposed as a potential cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We used the SCID-hu Thy/Liv mouse model to evaluate the in vivo interactions between HHV-6 and HIV-1. Our results demonstrate that HHV-6 and HIV-1 can simultaneously replicate in the human thymus in vivo. In this model, however, the presence of one virus appears not to modify the replication or cytopathicity of the other.
Asunto(s)
Infecciones por VIH/complicaciones , VIH-1/fisiología , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 6/fisiología , Animales , Efecto Citopatogénico Viral , Proteínas de Unión al ADN/análisis , Citometría de Flujo , Proteína p24 del Núcleo del VIH/análisis , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 6/inmunología , Humanos , Inmunohistoquímica , Ratones , Ratones SCID , Linfocitos T/virología , Proteínas Virales/análisis , Replicación ViralRESUMEN
BACKGROUND: A rare subset of human immunodeficiency virus (HIV) lymphomas, known as primary effusion lymphomas (PELs), are high-grade tumors carrying human herpes virus 8. Mechanisms postulated to contribute to lymphomagenesis include impaired immune surveillance, alterations in hemopoietic regulatory pathways due to expressed viral genes, and acquisition of genomic alterations in regions of the genome that contain regulatory genes. In PEL, limited information exists about the nature of genome-wide aberrations in these rare lymphomas. METHODS: We used comparative genomic hybridization to detect regions of sequence gain and loss throughout the genome of 8 PEL cases. Regions of DNA sequence loss or gain were confirmed using forward and reverse hybridization and t-statistic analyses. RESULTS: Genomic aberrations were identified in 6 of 8 cases, including recurrent gain of sequence in chromosomes 12 [ish enh (12q22;12q23, 12q12;12q23)] in 3 of 8 cases and X [ish enh (X, Xp)] in 2 of 8 cases. CONCLUSIONS: DNA copy number changes occurred in a majority of PEL cases and are consistent with changes observed in other HIV lymphomas. These observations suggest that common genetic events may occur in HIV-associated lymphoid malignancies, but they probably do not contribute to the unique markers and morphology of PEL. Although individual genetic loci have been evaluated previously in a few PEL cases, to our knowledge this study represents the first reported genome-wide scan of copy number changes in these rare HIV-associated tumors.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 12 , Linfoma Relacionado con SIDA/genética , Cromosoma X , Mapeo Cromosómico , Humanos , Linfoma Relacionado con SIDA/clasificaciónRESUMEN
Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that may act as a cofactor in the progression of AIDS. Here, we describe the first small animal model of HHV-6 infection. HHV-6 subgroup A, strain GS, efficiently infected the human thymic tissue implanted in SCID-hu Thy/Liv mice, leading to the destruction of the graft. Viral DNA was detected in Thy/Liv implants by quantitative polymerase chain reaction (PCR) as early as 4 d after inoculation and peaked at day 14. The productive nature of the infection was confirmed by electron microscopy and immunohistochemical staining. Atypical thymocytes with prominent nuclear inclusions were detected by histopathology. HHV-6 replication was associated with severe, progressive thymocyte depletion involving all major cellular subsets. However, intrathymic T progenitor cells (ITTPs) appeared to be more severely depleted than the other subpopulations, and a preferred tropism of HHV-6 for ITTPs was demonstrated by quantitative PCR on purified thymocyte subsets. These findings suggest that thymocyte depletion by HHV-6 may be due to infection and destruction of these immature T cell precursors. Similar results were obtained with strain PL-1, a primary isolate belonging to subgroup B. The severity of the lesions observed in this animal model underscores the possibility that HHV-6 may indeed be immunosuppressive in humans.
Asunto(s)
Herpesvirus Humano 6/inmunología , Timo/inmunología , Animales , Células Cultivadas , ADN Viral/análisis , Modelos Animales de Enfermedad , Herpesvirus Humano 6/metabolismo , Humanos , Inmunohistoquímica , Inmunosupresores/inmunología , Ratones , Ratones SCID , Microscopía Electrónica , Subgrupos de Linfocitos T/inmunología , Timo/patología , Timo/virología , Trasplante de Tejidos , Tropismo/inmunología , Replicación Viral/genéticaRESUMEN
Paraneoplastic pemphigus has been associated with both malignancies and multicentric Castleman's disease; the latter is a rare angiolymphoproliferative disorder that has also been linked with human herpesvirus 8 (HHV8) infection. Other diseases definitively associated with HHV8 include Kaposi's sarcoma and primary effusion lymphoma. In a search for additional HHV8-associated diseases, patients with paraneoplastic pemphigus, as well as patients with pemphigus vulgaris and pemphigus foliaceus, were studied. Using an immunofluorescence assay able to specifically detect antibodies directed against lytically induced HHV8 antigens, HHV8 antibodies were not detected in sera from 24 patients with paraneoplastic pemphigus (including 10 with concomitant Castleman's disease) nor from 19 patients with pemphigus vulgaris. Sera from patients with Kaposi's sarcoma and from healthy U.S. blood donors were positive (25 of 26) and negative (none of 20), respectively. In addition, HHV8 DNA was not found in frozen lesional skin of five patients with pemphigus vulgaris and five patients with pemphigus foliaceus by nested polymerase chain reaction (lower limit of detection = 10 copies viral DNA per microg total cellular DNA). Finally, tissue sections of lesional skin from 10 patients with pemphigus vulgaris were negative for HHV8 by in situ hybridization, using probes able to detect both latently and lytically expressed HHV8 genes in Kaposi's sarcoma tissue. In summary, no evidence of HHV8 infection was found in all types of pemphigus using a variety of methods. These findings do not support a general role for HHV8 in skin diseases associated with immunosuppression.
Asunto(s)
Infecciones por Herpesviridae/diagnóstico , Pénfigo/virología , Enfermedad de Castleman/sangre , Enfermedad de Castleman/complicaciones , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/complicaciones , Humanos , Síndromes Paraneoplásicos/sangre , Pénfigo/sangreRESUMEN
OBJECTIVE: To assess disease progression in baboons (Papio cynocephalus) that were infected with two human immunodeficiency virus-2 (HIV-2) isolates. METHODS: Eight baboons were inoculated intravenously with either HIV-2UC2 or HIV-2UC14 and were followed for a 2- to 7-year period of observation. RESULTS: Six of 8 baboons showed lymphadenopathy and other signs of HIV-related disease, 3 of 8 baboons had an acute phase CD4+ T-cell decline, and 2 of 5 baboons infected with the HIV-2UC2 isolate progressed to an acquired immunodeficiency syndrome-like disease. Human immunodeficiency virus-2-specific pathology in lymphatic tissues included follicular lysis, vascular proliferation, and lymphoid depletion. Both neutralizing antibodies and a CD8+ T-cell antiviral response were associated with resistance to disease. CONCLUSIONS: Disease progression and the development of acquired immunodeficiency syndrome in HIV-2-infected baboons have similarities to human HIV infections.
Asunto(s)
Infecciones por VIH/etiología , VIH-2 , Síndrome de Inmunodeficiencia Adquirida/patología , Animales , Anticuerpos Antivirales/análisis , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/inmunología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Fibroma/patología , Infecciones por VIH/patología , Infecciones por VIH/fisiopatología , VIH-2/inmunología , VIH-2/aislamiento & purificación , VIH-2/patogenicidad , Humanos , Hibridación in Situ , Enfermedades Linfáticas/patología , Masculino , Pruebas de Neutralización , Papio/virología , ARN Viral/análisis , Sarcoma de Kaposi/patología , Replicación Viral/inmunologíaRESUMEN
We have previously shown that baboons (Papio cynocephalus) can be persistently infected with HIV-2 and some baboons progress to an AIDS-like disease with a CD4+ T cell decline, cachexia, alopecia, and Kaposi's sarcoma-like fibromatosis. In this study, we found that a new virus isolate, HIV-2UC12, replicated to high levels in baboon peripheral blood mononuclear cells (PBMCs) in vitro. Three baboons were subsequently inoculated and had plasma viral RNA loads that peaked between 15,000 and 7000 copies/ml at 2 weeks postinfection. Virus was isolated from the PBMCs for up to 6 months. Although PBMCs were subsequently virus culture negative, virus could be recovered from the spleen, lymph nodes, and tonsils, indicating that HIV-2 was sequestered within these lymphoid tissues. HIV-2-associated pathology included follicular lysis, vascular proliferation, and lymphoid depletion. This study indicated that HIV-2UC12 infection in baboons can cause HIV-associated pathological abnormalities within the lymphatic tissues and that the high level of HIV-2UC12 replication in vitro was not predictive of replication in vivo.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/virología , VIH-2/patogenicidad , ARN Viral/metabolismo , Replicación Viral , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/patología , Animales , VIH-2/crecimiento & desarrollo , VIH-2/fisiología , Humanos , Sistema Linfático/patología , Sistema Linfático/virología , PapioRESUMEN
The body-cavity-based lymphoma cell line BCBL-1, which is infected with Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8, was injected alone or with human peripheral blood mononuclear cells into SCID mice. Immunoblastic lymphomas developed at or near the site of injection. The lymphomas appeared to derive exclusively from the injected BCBL-1 cells and not from the injected human PBMC. The tumors elicited a marked murine angiogenic response, but known angiogenic cytokines were not detected in BCBL-1 cells. Transfer of BCBL-1 cells to SCID mice may represent an in vivo model for the study of KSHV/HHV8-stimulated angiogenesis.
Asunto(s)
Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/fisiología , Transfusión de Linfocitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Animales , Antígenos CD/análisis , Citocinas/biosíntesis , Regulación Neoplásica de la Expresión Génica , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/patología , Humanos , Inmunofenotipificación , Interleucinas/biosíntesis , Linfocitos/virología , Ratones , Ratones SCID , Neovascularización Patológica , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Sarcoma de Kaposi/virología , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
The pathogenesis of polyclonal HIV-associated lymphomas lacking traditional B cell cofactors (i.e., Epstein-Barr virus [EBV] infection, c-myc translocations) is poorly understood. A multistep pathogenesis model has been proposed in which polyclonal lymphomas represent an earlier stage in HIV-associated lymphomagenesis before the emergence of a dominant malignant clone. Chronically present antigens have been proposed as a likely stimulus for polyclonal B cell proliferation; if so, polyclonal lymphoma-associated immunoglobulins (Igs) should have molecular evidence of somatic hypermutation, a process by which antibody affinity maturation in response to chronic antigenic stimulation occurs. Molecular analyses of Ig heavy chain variable (V(H)) gene use by B cells in a polyclonal HIV-associated large cell lymphoma lacking EBV and c-myc rearrangement was undertaken. Eighteen randomly selected clones generated from RT-PCR yielded 15 unique V(H) sequences, all of which were most homologous to only three previously identified germline V(H)1 genes. Two sets of clones (consisting of three and two clones, respectively) had identical V(H) gene sequences, and one pair of clones had identical third complementarity determining regions (CDR3s) but different V(H) gene sequences; eight clones were <95% homologous to their most related germline V(H)1 genes. We compared these results with Ig V(H)1 gene use by B cells present in a reactive hyperplastic lymph node obtained from an HIV-1-infected individual. Fifteen clones randomly selected from RT-PCRs yielded 15 unique V(H)1 sequences, all of which were most homologous to 5 previously identified germline V(H)1 genes; 10 clones were <95% homologous to their most related germline gene. Binomial probability analysis revealed that only 1 of the 15 unique V(H)1 sequences derived from the polyclonal lymphoma (i.e., 7%), as compared with 5 of 15 unique V(H)1 sequences derived from the reactive lymph node (i.e., 33%), had a low probability of occurrence by random chance (p < 0.05). These data provide molecular evidence of polyclonality in an HIV-associated polyclonal lymphoma, demonstrate a qualitative difference in somatic hypermutations of Ig V(H) genes associated with malignant versus reactive B cell lymphoproliferations, and support an antigen-mediated multistep pathogenesis model of HIV-1-associated lymphomagenesis.
Asunto(s)
Infecciones por VIH/inmunología , VIH-1/inmunología , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Linfoma Relacionado con SIDA/inmunología , Secuencia de Aminoácidos , Antígenos CD/análisis , Secuencia de Bases , Southern Blotting , ADN Viral , Infecciones por VIH/genética , Infecciones por VIH/patología , Humanos , Linfoma Relacionado con SIDA/genética , Linfoma Relacionado con SIDA/patología , Datos de Secuencia Molecular , Homología de Secuencia de Ácido NucleicoRESUMEN
To investigate the origin and pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL), we studied 14 cases in which Epstein-Barr virus (EBV) infection was not an etiologic factor. By histology, 8 of the specimens were of the small noncleaved cell type and 6 consisted of the large diffuse cell type. Southern analysis using a J(H) probe was consistent with a monoclonal B-cell tumor in 13 cases. To characterize the expressed Ig genes, we performed reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing of PCR products. Eight cases expressed IgM and 1 case expressed IgG. V(H)3 genes were found in 5 cases, V(H)4 genes in 3 cases, V(H)1 genes in 2 cases, and a V(H)7 gene in 1 case. The nucleotide homology to known germline V(H) genes ranged from 80% to 97%, suggesting significant somatic diversification of expressed V(H) genes. The large proportion of V(H)3-expressing lymphomas in this series corresponds to the frequency of V(H)3-expressing B cells in the peripheral blood from healthy and (recent) human immunodeficiency virus (HIV)-seropositve individuals and contrasts with the V(H)3 clonal deficit observed in late stages of HIV infection. Similar to the Ig heavy chain genes, the corresponding Ig light chain genes showed significant deviation from known germline gene sequences. The large proportion of V(H)3-expressing lymphomas as well as the high degree of somatic deviation from germline suggest that these EBV-negative lymphomas might arise from antigen-selected expanded B-cell clones before transformation. Further support for this hypothesis is provided by sequential Ig sequence analysis in 1 patient with large-cell lymphoma. It was shown that 3 years before the diagnosis of axillary lymphoma, there existed several B-cell clones in this patient's bone marrow. One of these clones present in the bone marrow expressed the same rearranged V(H) gene as the axillary lymphoma. Taken together, the current findings from Ig gene analyses suggest that activation of B cells in the early phase of HIV infection may be a predisposing factor for subsequent B-cell transformation.
Asunto(s)
Linfocitos B/inmunología , Linfoma Relacionado con SIDA/inmunología , Linfoma Relacionado con SIDA/virología , Secuencia de Aminoácidos , Secuencia de Bases , Genes de Inmunoglobulinas , Humanos , Activación de Linfocitos , Linfoma Relacionado con SIDA/genética , Masculino , Datos de Secuencia Molecular , Homología de Secuencia de AminoácidoRESUMEN
Primary malignant lymphomatous effusions arising in individuals infected with the human immunodeficiency virus, type 1 (HIV-1) represent a rare subset of HIV-associated lymphomas. Previous studies have demonstrated that the malignant cells are monoclonal (as defined by rearrangement of the immunoglobulin gene), express cell surface CD38, and are infected with Epstein-Barr virus (EBV) and human herpes virus, type 8 (HHV-8). Despite these detailed molecular and immunophenotypic studies, clinical information on this disease entity is scant, prompting us to review the clinical features of eight cases seen at our institutions. All eight patients had total peripheral CD4+ lymphocytes < 200/microliter and presented with complaints related to body cavity distension. Routine laboratory values were nondiagnostic and yielded no prognostic information. Only two patients could tolerate and thus received chemotherapy with no obvious impact on their clinical course. The mean overall survival after diagnosis was 60 days (range 6-166 days). Four patients were examined at autopsy. The primary malignant lymphomatous effusion either was the immediate cause of death or contributed significantly to the death of only two. All four patients examined post mortem, however, had lymphomatous infiltration of serosal surfaces adjacent to the site of the primary malignant effusion. Molecular and immunologic studies performed on the malignant cells and effusion fluids revealed universal expression of cell surface CD38 and the presence of HHV-8 gene sequences, but in contrast with previous studies, only four had rearranged immunoglobulin genes or EBV present: IL-6 and IL-10 levels in the malignant effusion fluids were markedly elevated. In summary, this rare subset of HIV-associated lymphomas in our eight patients arose late in the course of HIV-associated disease, had a rapid clinical course, and was molecularly heterogeneous. A pathogenetic role for HHV-8 alone in this disease process is strengthened by our observation of four cases lacking EBV but containing HHV-8.
Asunto(s)
Antígenos CD , Infecciones por VIH/complicaciones , VIH-1 , Linfoma/epidemiología , Linfoma/etiología , ADP-Ribosil Ciclasa , ADP-Ribosil Ciclasa 1 , Adulto , Antígenos de Diferenciación/análisis , Líquido Ascítico/citología , Líquido Ascítico/inmunología , Líquido Ascítico/virología , Autopsia , Southern Blotting , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Herpesvirus Humano 4/genética , Herpesvirus Humano 8/genética , Humanos , Cambio de Clase de Inmunoglobulina , Interleucina-10/análisis , Interleucina-6/análisis , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Linfoma/diagnóstico , Masculino , Glicoproteínas de Membrana , Persona de Mediana Edad , N-Glicosil Hidrolasas/análisis , Reacción en Cadena de la Polimerasa , Células Tumorales CultivadasRESUMEN
We report Hodgkin's disease arising in a 68-year-old patient with a history of chronic lymphocytic leukemia for 8 years. The patient presented with a 4-month history of weakness, loss of appetite, and a 15-pound weight loss. A bone marrow biopsy showed two distinct histologic types of lymphoma: chronic lymphocytic leukemia and Hodgkin's disease. Immunohistochemical studies showed that chronic lymphocytic leukemia cells were composed of kappa-light chain-restricted monoclonal B cells. The Reed-Sternberg cells expressed CD15. Epstein-Barr virus RNA was not identified in either the Reed-Sternberg cells or cells of chronic lymphocytic leukemia by in situ hybridization. To our knowledge, this is the second reported case of composite Hodgkin's disease and chronic lymphocytic leukemia involving the bone marrow.
Asunto(s)
Neoplasias de la Médula Ósea/patología , Enfermedad de Hodgkin/patología , Leucemia Linfocítica Crónica de Células B/patología , Neoplasias Primarias Múltiples/patología , Anciano , Antígenos CD20/análisis , Biopsia , Femenino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Hibridación in Situ , Antígeno Lewis X/análisis , ARN Viral/análisis , Células de Reed-Sternberg/patologíaRESUMEN
BACKGROUND AND DESIGN: Most non-Hodgkin's lymphomas in patients with human immunodeficiency virus infection are of B-cell lineage. Cutaneous lymphoma in the human immunodeficiency virus disease has not been systematically reviewed. We studied 25 patients with both human immunodeficiency virus infection and cutaneous presentations of lymphoma, using immunohistochemistry and in situ hybridization for Epstein-Barr virus. RESULTS: Two groups of patients were discerned: (1) those with conditions similar to mycosis fungoides or Sézary syndrome with an indolent course (n = 8) and (2) those with nodules or papules, greater immunosuppression, a rapid clinical course, and large cell lymphoma seen on biopsy specimens (n = 17). The epidermotropic lymphomas were T-cell lineage and CD30-. Thirteen of the large cell lymphomas were also of the T-cell type, and 71% were CD30+. Epstein-Barr virus was absent in the epidermotropic lymphomas, but it was present in 73% of the nonepidermotropic cases. CONCLUSIONS: Two forms of human immunodeficiency virus-associated cutaneous lymphoma were found: indolent disease resembling mycosis fungoides or Sézary syndrome and large cell lymphomas with a poor prognosis, whose cells often had a CD30+ T-cell phenotype and harbored the Epstein-Barr virus.
Asunto(s)
Linfoma Relacionado con SIDA/patología , Linfoma Cutáneo de Células T/patología , Neoplasias Cutáneas/patología , Adulto , Humanos , Inmunofenotipificación , Persona de Mediana Edad , Micosis Fungoide/patología , Síndrome de Sézary/patologíaAsunto(s)
Anticuerpos Antineoplásicos/genética , Subgrupos de Linfocitos B/metabolismo , Regulación Neoplásica de la Expresión Génica , Reordenamiento Génico de Cadena Pesada de Linfocito B , Genes de Inmunoglobulinas , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Linfoma Relacionado con SIDA/genética , Subgrupos de Linfocitos B/patología , Antígenos CD5 , Células Clonales/metabolismo , Células Clonales/patología , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Humanos , Ganglios Linfáticos/patología , Linfoma Relacionado con SIDA/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Reacción en Cadena de la Polimerasa , Estudios ProspectivosRESUMEN
We recently reported clonal human immunodeficiency virus (HIV involvement in four acquired immune deficiency syndrome (AIDS)-associated non-B-cell lymphoproliferations. In three of these cases HIV expression was localized to tumor-associated macrophages. Because one of the cases had a major component involved in angioproliferation, we speculated that some form of Kaposi's sarcoma (KS), which also has a major component of angioproliferation, might be involved clonally with HIV. The current study is an evaluation of four cases of KS and control tissues taken from four patients who died with complications of HIV disease. With use of the inverse polymerase chain reaction technique to identify clonal forms of HIV, a clonal form of HIV was found in one of four KS cases. The HIV-positive tumor was an early KS lesion of the bowel, and uninvolved bowel from the same patient showed no clonal HIV. Immunohistochemical analysis demonstrated the presence of prominent HIV-expressing macrophages that also coexpressed high levels of HIV tat, basic fibroblast growth factor, and interleukin-6. These data provide evidence for a pathogenic process termed "sequential neoplasia," wherein a clonal macrophage provides a growth factor milieu stimulating the proliferation of a responder cell population that ultimately becomes autonomous. In the current case, the macrophages expressing HIV were located adjacent to the KS tumor tissue and were found to be producing known KS growth factors. The absence of finding clonal HIV in three more advanced KS lesions suggests that the clonal macrophage may be required only for early pathogenesis and that sequential neoplastic changes occurring in the endothelial cells gave rise to autonomous KS.(ABSTRACT TRUNCATED AT 250 WORDS)