Persistent Generalized Lymphadenopathy Research Articles

STUDY OF LYMPH NODE CYTOLOGY IN HIV INFECTED PATIENTS

Background and Aim: Human immunodeficiency virus (HIV) infection has become a global pandemic. Persistent generalized lymphadenopathy (PGL) is very common manifestation of HIV infection. Moreover, different opportunistic infections such as tuberculosis (TB) and malignancies may present with lymphadenopathy. This study was performed to evaluate the role of FNAC as a cytological investigative tool in the diagnosis of various lesions in HIV lymphadenopathy.
 Material and Methods: This study was carried out in Tertiary care Institute of India, over a period of one year. Total 50 cases of HIV lymphadenopathy patients were participated in the study after having signed the Informed Consent Form. Diagnosis of HIV was done by enzyme linked immunosorbant assay (ELISA) test, followed by the CD4 counts by BD FACS Count system in HIV positive patients. FNAC procedure was performed as an OPD procedure in cytology OPD of pathology department.
 Results: Most common site of HIV lymphadenopathy is cervical lymph node 40 (80%), followed by supraclavicular 6(12%) followed by axillary lymph node 4(8%). The most common lesion found was mycobacterial infection 22(44%), followed by reactive lymphadenitis 15(30%). Non-specific chronic granulomatous lymphadenitis in 10(22%) and 3(6%) cases of acute suppurative lymphadenitis. CD4 count more than 500 cells/ µL was seen in 9 (18%) cases of reactive lymphadenitis and 4 (8%) cases of chronic granulomatous lymphadenitis. Patients with tubercular infection had CD4 count between 200- 499 cells/ µL in 12 (24%) cases and less than 200 in 10 (20%) cases.
 Conclusion: FNAC is relatively inexpensive and valuable tool for identification of opportunistic infections, neoplastic lesions and non-neoplastic lesions. It may spare patients lymph node excision and enable immediate treatment of specific infection. This procedure is readily repeatable and can be used for follow up during and after treatment.
 Keywords: Human immunodeficiency virus, lymphadenopathy, Non-specific chronic granulomatous lymphadenitis, tuberculosis

Clinical Course of Opportunistic Infections-Toxoplasmosis and Cytomegalovirus Infection in HIV-Infected Patients in Slovakia.

The HIV/acquired immunodeficiency syndrome (AIDS) pandemic has affected the health status of the population in many countries. Early symptomatic HIV infection includes persistent generalized lymphadenopathy (PGL), which can be associated with opportunistic infections, e.g., toxoplasmosis and Cytomegalovirus (CMV) infection. This study followed the occurrence of PGL, toxoplasmosis, and Cytomegalovirus infection in 32 HIV-positive patients and analyzed the clinical signs of disease in relation to the number of CD4 T lymphocytes. In monitored patients, the average number of CD4 T lymphocytes was 940.8 ± 396.7/µL of blood. Severe immunodeficiency was recorded in four persons, who also suffered from colitis and/or retinitis and pneumonitis. The number of CD4 T cells in patients with PGL was significantly lower than that in patients without lymphadenopathy. In 6 (18.8%) IgM and 11 (34.4%) IgG Toxoplasma gondii seropositive patients, the number of CD4 T lymphocytes was significantly lower than that in seronegative patients. The presence of IgM and IgG antibodies to Cytomegalovirus was recorded in all examined patients, and CMV infection clinically manifested in five persons. The occurrence of PGL, the higher viral load, and seropositivity to T. gondii were significantly related to decline in the CD4 T lymphocyte number. The clinical course of the diseases was influenced by the status of the patient’s immunodeficiency and suggests ongoing immunosuppression and possible reactivation of both infections in all patients.

СРАВНИТЕЛЬНЫЙ АНАЛИЗ ГИСТОЛОГИЧЕСКОЙ И ИММУНОГИСТОХИМИЧЕСКОЙ КАРТИНЫ ЛИМФАТИЧЕСКИХ УЗЛОВ ПРИ ВИЧ-ИНФЕКЦИИ

Background. Structural changes in the lymph nodes (LNs) in HIV infection correspond to the clinical syndrome – persistent generalized lymphadenopathy (PGL), which is a fairly reliable clinical sign of HIV infection. As a result of prolonged PGL in the germinal centers of the lymph nodes, cytopathic destruction of immunocompetent cells occurs, leading to their involution. The goal is to establish histological and immunohistochemical parallels in LN at different clinical stages of HIV infection. Material and methods. The object of the study was 48 LNs of various locations from 13 dead HIV-infected patients in Svetlogorsk district of Gomel region in 2018, as well as 4 LNs after an excisional biopsy of 4 patients from this region. Before immunohistochemical examination (IHC), all histological preparations were studied by light microscopy using staining with hematoxylin and eosin (H&E), which enabled to assess the state of structural elements in the lymph nodes. IHC of lymph nodes was performed using the following antibodies (manufactured by Roche Diagnostics, USA): rabbit monoclonal primary antibodies to CD3 (2GV6), CD4 (SP35), CD10 (SP67), bcl-2 (SP66), as well as mouse monoclonal primary antibodies CD20 (L26), CD21 (2G9). The IHC study was performed using a VentanaBenchMark GX IHC / ISH automatic immunohistostainer. Results. In most cases, the relationship and the coincidence of histological and immunohistochemical changes in the LNs taking into account the stage of PGL were established. The revealed changes corresponded to successive stages of PGL from severe hyperplasia of lymphoid follicles with wide germinal centers at the initial stages of infection to hypoplasia of reproduction centers and complete atrophy of lymphoid follicles (lymphocytic depletion), which is reflected in the illustrations. The reproducibility control of the results of the PGL stages according to the IHC results was 100%, in contrast to light microscopy, the results of which corresponded to the PGL stages in 82.3%. Conclusions. The histological picture of LNs in patients with HIV infection in most cases correlates with the immune status data, but it does not have absolute value in the diagnosis of PGL stage. The IHC study has higher reliability and reproducibility than a histological study in determining the stages of PGL. A complex method of histological and immunohistochemical studies improves the quality of diagnosis of HIV infection in general.

Etiological study of lymphadenopathy in HIV-infected patients in a tertiary care hospital.

Introduction:Human immunodeficiency virus (HIV) infection has become a global pandemic. Persistent generalized lymphadenopathy (PGL) is very common manifestation of HIV infection. Moreover, different opportunistic infections such as tuberculosis (TB) and malignancies may present with lymphadenopathy. Mycobacterium avium complex (MAC) infection is most common with cluster of differentiation (CD)4+ count ≤50 cells/μL. Fine-needle aspiration cytology (FNAC) offers a simple and effective modality for obtaining a representative sample of the material from lymph nodes, permitting cytological evaluation and other investigations.Aims and Objectives:The aim of this study is to find out the different etiologies of lymphadenopathy in HIV-infected patients and to establish a possible correlation with CD4+ count.Materials and Methods:A total of 100 HIV-infected patients having significant (>1 cm) extrainguinal lymphadenopathy were studied in 1 year at the Department of Pathology by FNAC and the stains used were Leishman–Giemsa, Ziehl–Neelsen (ZN), Papanicoloau, and Gram stains. For tubercular culture, Löwenstein–Jensen (LJ) medium was used. CD4+count was done by flow cytometer.Result:The present study revealed four types of cytomorphological variants in lymphadenopathy cases by FNAC, which include: Reactive hyperplasia and caseation necrosis; caseation necrosis and ill-formed granuloma; well-formed granuloma without any necrosis; and non-Hodgkin lymphoma (NHL). The highest acid-fast bacilli (AFB) positivity was among the patients showing caseation necrosis. Tubercular culture in LJ media turned out as a more sensitive method for diagnosis than routine ZN staining. The 2 cases that showed well-formed epithelioid granuloma without any necrosis turned out to be histoplasmosis and cryptococcosis, respectively. In this study, we found 2 cases of NHL. The study also revealed that caseation necrosis and AFB positivity along with opportunistic infections increases with decreased CD4+ count.

HIV-associated salivary gland disease--clinical or imaging diagnosis?

This work aimed at studying the salivary gland disease (SGD) as it relates to associated factors, such as persistent generalised lymphadenopathy (PGL), lymphocytic interstitial pneumonia (LIP), clinical and immunological features of AIDS, and salivary flow rate and pH, as well as at exploring the relationship between the clinical diagnosis and the imaging diagnosis by ultrasound (US) examination of the parotid glands. Information regarding the observation of parotid gland enlargement, PGL, LIP, and clinical and immunological features of AIDS was gathered from medical records, and a saliva sample for unstimulated salivary flow rate and pH measurement was collected from 142 children aged 3 through 10 years treated at the Department of Infectious Diseases of Joana de Gusmão Children's Hospital, Florianópolis, SC, Brazil. High-resolution ultrasonography was performed in 58 children. Pearson's chi-square test and t-test were used to evaluate the association between the variables. A significant association was found between SGD and LIP. Ultrasound revealed a 50% higher incidence of SGD that was not reported in the patients' records. US examination proved to be essential for the correct diagnosis and monitoring of the progression of HIV/SGD.

Evaluation of Epstein-Barr virus (EBV) and human herpes virus-8 (HHV-8) in HIV-associated persistent generalized lymphadenopathy (PGL)

Background Human immunodeficiency virus (HIV) infection is associated with persistent generalized lymphadenopathy (PGL) resulting from polyclonal B cell activation with significant circulating Epstein-Barr virus (EBV). Does HHV-8 contribute to the hyperplasia when present? Unlike EBV, seroprevalence of HHV-8 in the HIV-negative U.S. population is low. Kaposi's sarcoma (KS) in HIV infected is thought to reflect de novo HHV-8 infection, not reactivation. Does primary HHV-8 infection present as a polyclonal B cell activation manifested as PGL such as other HHV-8 associated co-morbidities like primary effusion lymphoma and multicentric Castleman's disease? This study examines the association of HHV-8 (LANA-1) with B cells in HIV-associated PGLs.

Epstein-Barr virus and HIV play no direct role in persistent generalized lymphadenopathy syndrome.

Persistent generalized lymphadenopathy (PGL) and polyclonal B cell activation are features of infection with HIV. Epstein-Barr virus (EBV) and HIV are known to activate B cells in vitro, but whether they are important B cell activators in patients infected with HIV is less clear. In this study, lymph node tissue was obtained from 10 patients with PGL and assessed for evidence of EBV and HIV gene sequences. DNA was extracted and specific viral gene sequences identified using the polymerase chain reaction (PCR). EBV sequences were difficult to detect in the PGL tissue, with a signal intensity similar to that of other benign and malignant lymphoid conditions not associated with EBV. HIV sequences were also rare in the PGL tissue, consistent with HIV infection of the small number of peripheral blood cells and nodal T cells likely to be present in such a sample. These findings suggest that the polyclonal B cell activation typical of HIV is not driven by direct EBV or HIV infection of B cells.

Disturbed immunoregulatory properties of the neuropeptide substance P on lymphocyte proliferation in HIV infection.

The neuropeptide substance P (SP) is known to increase cell-mediated immune responses in animal models and healthy subjects. Several studies have suggested an involvement of neuropeptides in the immunopathogenesis of some diseases. The study of the immunomodulatory effects of neuropeptides, namely SP, may represent a model for the analysis of immunoregulatory defects in HIV infection at the level of the interaction between the immune and nervous systems, both of which are known to be affected by the virus. In the present study, we investigate the possibility of a disturbance in the immunomodulatory properties of SP in HIV infection by analysing the effects of SP (10(-10)-10(-6) M) on the lymphocyte proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA) assessed by 3H-thymidine incorporation in peripheral blood lymphocytes from 34 HIV-infected patients (16 asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY/PGL HIV-infected patients, SP 10(-7) M was identified as the concentration inducing the maximal increase in the lymphocyte responses to Con A and PHA, similarly to what was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit the mitogenic responses, particularly those induced by Con A, in contrast to the effects found either in healthy subjects or in ASY/PGL patients. These results suggest the existence of an alteration in the in vitro immunomodulatory properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL patients. In conclusion, the unexpected finding of an inhibitory effect of SP on lymphocyte proliferation from ARC/AIDS patients justifies further investigation of the neuropeptide-dependent immunoregulatory systems in HIV infection.

The Benign Lymphoepithelial Cyst and a Classification System for Lymphocytic Parotid Gland Enlargement in the Pediatric HIV Population

The objectives of this study are to present a series of parotid gland benign lymphoepithelial cysts (BLEC) in HIV-positive children and to propose a three-tiered classification system for HIV-associated lymphocytic parotid gland enlargement. The authors conducted a retrospective case series and literature review. The authors conducted a retrospective chart review of four pediatric patients with HIV-associated parotid gland BLEC who presented to a tertiary care university medical center. Four pediatric HIV-positive patients (four girls; age range, 7-17 years [mean age, 12.8 years]) were diagnosed with parotid gland BLEC. Two patients presented with acute parotitis and the others presented with asymptomatic enlargement of the parotid glands. Three patients had bilateral parotid gland BLEC. The other patient demonstrated persistent generalized lymphadenopathy (PGL) of the intraparotid and cervical lymph nodes and early BLEC limited to the left parotid gland. One patient also displayed parotid gland microcalcifications and cystic changes in the adenoids, neither of which have been described previously in the setting of HIV-associated BLEC. Computed tomography was performed on all patients, and one patient underwent fine needle aspiration to confirm the diagnosis. All patients opted for observation and antiretroviral medication therapy as long-term treatment. Based on these findings and a review of the literature, we propose a three-tiered classification system for lymphocytic parotid gland enlargement in the HIV population: 1) PGL, 2) benign lymphoepithelial lesions (BLEL), and 3) BLEC. This series equals the largest pediatric series of HIV-associated parotid gland BLEC in the English literature. One patient in our series also demonstrated PGL; there were no cases of BLEL. A classification system based on morphology is proposed to help resolve the confusion in terminology used to describe this entity. Most pediatric HIV-infected patients with parotid gland BLEC can be treated with observation and antiretroviral medication therapy. For others, who are symptomatic or more concerned about their cosmetic appearance, sclerotherapy may offer a reasonable option. Radiation therapy and surgery should be reserved for select cases.

Persistent Generalized Lymphadenopathy (PGL) Mimicking Lymphoma on Whole-Body FDG PET/CT Imaging

We present PET/CT images of a 42-year-old HIV-positive man who presented with generalized lymphadenopathy and systemic symptoms suggestive of lymphoma. Whole-body PET/CT revealed hypermetabolic lymphadenopathy bilaterally in the neck, axilla, and inguinal regions, and hypermetabolism in an enlarged spleen. These findings were thought to be typical for lymphoma. The biopsy of right axillary lymph nodes showed no evidence of lymphoma but findings characteristic of persistent generalized lymphadenopathy (PGL).

Clinical investigations of lymphadenopathy, including lymph node biopsies, in 24 homosexual men with antibodies to the human T-cell lymphotropic virus type III (HTLV-III).

The findings of 27 lymph node biopsies performed on 24 homosexual patients with lymphadenopathy are presented. Six had acquired immune deficiency syndrome (AIDS) and 18 lymphadenopathy only, of whom one subsequently developed AIDS. All these patients had antibodies to the human T-cell lymphotropic virus type III (HTLV-III) suggesting that HTLV-III is currently the commonest cause of lymphadenopathy in homosexual men. The histopathological findings of six of seven nodes from AIDS patients showed either follicular depletion alone or follicular and paracortical lymphocyte depletion. Nodes from four patients showed Kaposi's sarcoma, three of which also showed follicular hyperplasia. In two of these patients there were no cutaneous manifestations of this condition. One lymph node from a patient with persistent generalized lymphadenopathy (PGL) showed Mycobacterium tuberculosis. Six nodes from six other patients have had features of toxoplasmosis although there was no serological or clinical evidence of recent toxoplasma infection. The remaining 11 lymph nodes from patients with PGL and one node from a patient with transient lymphadenopathy, showed reactive follicular hyperplasia only. We conclude that homosexuals with lymphadenopathy who are HTLV-III antibody positive do not need a routine node biopsy unless an alternative diagnosis is strongly suspected.

BETA-2-MICROGLOBULIN LEVELS IN HUMAN-IMMUNODEFICIENCY VIRUS INFECTED SUBJECTS

We studied beta-2 microglobulin (β-2M) levels in 44 HIV infected subjects belonging to 3 clinical stages as well as in 25 healthy controls. The method used was a competition enzyme immunoassay. In this study, levels of β2-M were measured in two groups of HIV infected individuals, the asymptomatic and those with progressive and advanced disease, in order to affirm its role as a surrogate prognostic marker. It was found that mean β-2M levels were 1.28 mg/L in the controls (normal range 0-2.4 mg/L), 11.41 mg/L in the HIV infected subjects, 2.69 mg/L in the asymptomatic HIV infected, 12.14 mg/L in those with persistent generalized lymphadenopathy (PGL) and 39.29 mg/L in the patients with acquired immunodeficiency syndrome. It was concluded that β-2M levels were significantly higher in the HIV infected as compared to the controls. Further, the levels were much higher in the HIV infected with progressive diseasc/PGL and highest in those who had developed AIDS. β-2M is an important surrogate serological marker useful in prognostication of disease process in the HIV infected. Advantages of measuring β-2M levels over p24 antigen detection and CD4 counts were highlighted.

Effects of smoking and clinical status on lung function in human immunodeficiency virus (HIV)-seropositive subjects

Lung function was measured at 3-month intervals for up to 1 yr in a group of Caucasian HIV-seropositive subjects. The objective was to document any deterioration in lung function and seek correlations between such deterioration and smoking history and Centers for Disease Control (CDC) status. Ninety-nine subjects were studied at enrolment; 43 were followed-up (mean duration 9 ± 3 months). Ninety-five of the 99 enrolled subjects remained free of HIV-related respiratory disease and were included in the analysis. At enrolment, carbon monoxide diffusing capacity ( T lCO) was significantly lower than predicted in non-smokers, smokers and ex-smokers (88, 77 and 88%, respectively, P<0·001). The T lCO measurements in the smoking group were significantly lower than those of the life-long non-smoking subjects ( P<0·01). Residual volume (RV) was significantly higher than predicted in smokers (111%, P=0·02). During follow-up, all three groups demonstrated significant declines in T lCO (7%, P=0·01; 9%, P=0·005; 13%, P<0·001, respectively), and increases in RV (9%, P=0·03; 13·5%, P=0·02; 22%, P=0·02, respectively). At enrolment, significantly lower than predicted values of T lCO were observed in groups stratified by CDC criteria: in asymptomatic HIV-seropositive subjects (CDC II) 89%, p=0·01; persistent generalized lymphadenopathy (PGL) 84%; AIDS-related complex (ARC) 81%; and in non-pulmonary AIDS (IV C1) 69%, P=0·0001, respectively. Residual volume was significantly higher than predicted in CDC II (114%, P=0·05). During follow-up, T lCO fell in groups PGL and ARC by 7 and 9%, respectively, while RV increased in groups CDC II, PGL and ARC by 17, 15 and 8%, respectively. Only the T lCO decline in PGL showed any linkage to clinical deterioration. This study demonstrates deficits at enrolment, and a continuing decline of T lCO and increase in RV in HIV-seropositive subjects without overt lung disease.

Human Herpesvirus-8 DNA Sequences in Human Immunodeficiency Virus-Negative Angioimmunoblastic Lymphadenopathy and Benign Lymphadenopathy With Giant Germinal Center Hyperplasia and Increased Vascularity

Human herpesvirus-8 (HHV-8) DNA sequences have been reported to be strictly associated not only with various forms of Kaposi's sarcoma but also with an unusual subgroup of acquired immunodeficiency syndrome (AIDS)-related B-cell lymphomas. A possible relation of this putative virus also with multicentric Castleman's disease (MCD) has been recently suggested. We used polymerase chain reaction to look for the presence of HHV-8 sequences in a well characterized series of benign, atypical, and malignant lymphoid tissues from 45 Hodgkin's disease and 43 non-Hodgkin's lymphoma (NHL) cases, as well as from 5 MCD, 15 angioimmunoblastic lymphadenopathy (AILD), and 23 benign lymphadenopathy cases. Among the 38 AIDS-related lymphoid lesions, only 1 NHL and 1 persistent generalized lymphadenopathy (PGL) case were positive. Furthermore, among the 92 non-AIDS-related lymphoproliferative disorders, HHV-8 sequences were detected in 3 classic AILD cases and in 4 reactive lymphadenopathies. Six of 9 HHV-8 positive lymphoid lesions (1 NHL, 1 PGL, 1 AILD, and 3 reactive lymphadenopathy cases) were also positive for Epstein-Barr viral sequences. The four human immunodeficiency virus (HIV) negative lymphadenopathies positive for HHV-8 sequences showed an almost identical histology, characterized by a predominantly follicular lesion, with giant germinal center hyperplasia, and increased vascularity, resembling HIV-related lymphadenopathy and MCD. Our results, while providing the first evidence of the presence of HHV-8 sequences in AILD cases, suggest a possible association of these herpes viral sequences with a distinct histologic type of non-neoplastic lymphadenopathy, not associated with other common herpes infections.

Molecular Pathogenesis of Aids-Related Lymphomas

Publisher Summary This chapter focuses on the molecular pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphomas. Non-Hodgkin's lymphoma (NHL) is the second most frequent cancer associated with AIDS after Kaposi's sarcoma (KS), and in some AIDS-risk groups, such as the hemophiliacs, NHL overrates KS, thereby representing the most common AIDS-associated neoplasia. Various epidemiologic features distinguish AIDS-NHL from AIDS-related KS (AIDS-KS). First, AIDS-NHL is a relatively late event in AIDS natural history, whereas AIDS-KS is a frequent symptom. Second, AIDS-NHL displays a relatively uniform risk across all HIV-infected risk groups, whereas AIDS-KS is characterized by a strong association with male homosexuality. The detailed pathological classification of AIDS-NHL has been a matter of controversy, and it is continuously being remodeled. The development of B-cell NHL in the context of AIDS is often preceded by symptoms such as polyclonal hypergammaglobulinemia and persistent generalized lymphadenopathy (PGL), which indicate the presence of chronic B-cell stimulation and expansion. Host factors contributing to AIDS-related lymphoma genesis include Epstein–Barr virus (EBV), human immunodeficiency virus (HIV), and other viruses. Genetic lesions involved in AIDS-related lymphomas include dominantly acting oncogenes and tumor suppressor loci. AIDS-NHL is a strikingly heterogeneous disease. At least two major pathogenetic pathways can be identified in AIDS-related lymphomagenesis. Each of these pathogenetic pathways associates with peculiar clinical features and is restricted to distinct AIDS-NHL histological types.

Molecular pathology of AIDS-related lymphomas. Biologic aspects and clinicopathologic heterogeneity.

A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) is almost invariably derived from B cells and is classified as high- or intermediate-grade NHL, according to the working formulation. Two main histologic types are recognized, including small noncleaved cell lymphoma (SNCCL) and diffuse large cell lymphoma (DLCL). Pre-existing host factors putatively involved in lymphoma development include disrupted immunosurveillance, deregulated cytokine production, chronic antigen stimulation, and infection by Epstein-Barr virus (EBV). These alterations are associated with the development of multiple oligoclonal expansions which correspond to the clinical phase known as persistent generalized lymphadenopathy (PGL). The appearance of a true AIDS-NHL is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal EBV infection, c-MYC and BCL-6 rearrangements, RAS mutations, p53 inactivation, and 6q deletions. These genetic lesions cluster into two distinct molecular pathways, which specifically associate with the different histologic subtypes of AIDS-NHL, i.e., AIDS-SNCCL and AIDS-DLCL. The presence of distinct genetic pathways for AIDS-SNCCL and AIDS-DLCL correlate with a number of clinical features which distinguish these two groups of tumors, including differences in the age of onset, CD4 counts at the time of presentation, time elapsed since HIV infection, and clinical outcome.

Distinct alterations in the distribution of CD45RO+ T-cell subsets in HIV-2 compared with HIV-1 infection Ana C. Jaleco

Some clinical studies indicate that disease progression in HIV-2-infected subjects may be slower than in HIV-1. We investigated whether there were differences in the distribution of CD45RO+ (memory) and CD45RA+ (naive) T-cell subsets between HIV-1 and HIV-2 infection. Analysis of lymphocyte subsets was performed by flow cytometry in peripheral blood mononuclear cells from healthy controls, HIV-1-(n = 49) and HIV-2-infected (n = 47) individuals divided into two groups: asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL) and AIDS-related complex (ARC)/AIDS. Both HIV-1- and HIV-2-infected patients had significant reductions in the absolute number and percentage of CD4+ lymphocytes compared with seronegative individuals. No significant differences were found between HIV-2- and HIV-1-infected subjects in the same clinical stage. CD4+CD45RA+ cells were significantly reduced in HIV-1 and HIV-2 ARC/AIDS patients and mildly reduced in ASY/PGL HIV-1 and HIV-2 patients. There were no differences in the degree of reduction of CD4+CD45RO+ cells in ASY/PGL HIV-1 versus HIV-2 patients. However, in HIV-1-infected ARC/AIDS individuals the reduction in the percentage of this subset was more pronounced than in HIV-2 infection and this difference reached statistical significance. The increase in CD8+ lymphocytes (percentage and absolute number) was more pronounced in HIV-1 and the differences between HIV-1- and HIV-2-infected patients were statistically significant. CD8+CD45RO+ cells were significantly increased both in ASY/PGL and ARC/AIDS HIV-1-infected patients, whereas HIV-2-infected ASY/PGL patients had normal levels of these cells and HIV-2-infected ARC/AIDS patients had increases that were much less pronounced than that observed in HIV-1-infected ARC/AIDS patients. Significant differences in the absolute number and percentage of this subset between HIV-1- and HIV-2-infected individuals in similar clinical stages were found. HIV-2-infected individuals exhibit a lesser degree of depletion of memory CD4+ cells and a more limited expansion of CD8+CD45RO+ subset, which could be related to the putative lower immunopathogenicity of HIV-2.

Persistent generalized lymphadenopathy and non-Hodgkin's lymphoma in AIDS: association with Rochalimaea henselae infection

Cat scratch disease, which is caused by infection with Rochalimaea henselae, is often manifested as lymphadenopathy. R. henselae has also been isolated from human immunodeficiency virus (HIV)-positive patients with bacillary angiomatosis. In order to determine the frequency of R. henselae-reactive antibodies in HIV-positive patients with persistent generalized lymphadenopathy (PGL) or non-Hodgkin's lymphoma (NHL), we tested a total of 124 HIV-positive patients for R. henselae-reactive immunoglobulin G (IgG), IgM, and IgA antibodies by an enzyme immunoassay procedure using whole R. henselae antigen. Of the patients, 7 had PGL, 17 had NHL, and 100 were HIV stage IV (Centers for Disease Control criteria). A total of 86% of PGL patients (6 of 7) were positive for R. henselae antibodies (three were positive for IgG, IgA, and IgM, one was positive for IgG and IgA only, and two were positive for IgG only). A total of 29% of NHL patients (5 of 17) were positive for R. henselae antibodies (two were positive for IgG, IgA, and IgM and three were positive for IgG only). Only 5% of HIV Stage IV patients without adenopathy (5 of 100) were positive for R. henselae-reactive IgG, IgA, and IgM. The high prevalence of R. henselae-reactive antibodies in HIV-positive PGL and NHL patients suggests that R. henselae is a potential etiologic agent or cofactor in these patients.

Lymphocyte transformation responses to phytohaemagglutinin and pokeweed mitogen in patients at differing stages of HIV infection: are they worth measuring?

To determine whether the routine measurement of lymphocyte transformation responses to mitogenic stimuli provide any information additional to that available from routine T cell CD4 and CD8 analysis in patients with HIV infection. The case records of 197 immunologically investigated HIV seropositive patients were reviewed. The influence of disease stage on T lymphocyte subsets and lymphocyte transformation responses (LyTR) to phytohaemagglutinin (PHA) and Pokeweed mitogen was assessed. The median CD3 and CD4 counts and LyTR to PHA and Pokeweed mitogen were highest in patients with persistent generalised lymphadenopathy (PGL) and decreased progressively in the order: asymptomatic patients, those with ARC, those with AIDS. LyTR to PHA was preserved in over 70% of all patients, but the response to Pokeweed mitogen was depressed in 8% of patients with PGL, 34% of asymptomatic patients, 68% of those with ARC and 78% of those with AIDS. Subnormal values of both CD4 + T cells and LyTR to Pokeweed mitogen were more common in patients with ARC and AIDS (68%) than in those who were asymptomatic or had PGL (20%). CD4 T cell analysis and LyTR to Pokeweed mitogen, but not to PHA, both correlate with disease states in patients with HIV infection.

Ultrastructural analysis of human lymph node follicles after HIV-1 infection.

Infection with the human immunodeficiency virus type 1 (HIV-1) may result in persistent generalized lymphadenopathy (PGL). Lymph nodes in PGL most commonly show a florid follicular hyperplasia (FH) in which regressive changes, such as loss of mantle zones and fragmentation of the germinal centre (GC) can be observed.1,2 Fragmentation of the framework of follicular dendritic cells (FDC) has been demonstrated by immunohistochemistry.1,3 Intact HIV-1 virus particles are regularly found between the extensions of FDC within GCs of HIV-1 infected individuals.4,5 These observations have been associated with a cytopathic action of the virus on FDC.6,7 A proportion of FDC may be infected and produce virus.8 FDC function as accessory cells in GCs. Impairment of FDC function by cytopathic effects of the virus may influence GC microenvironment. The distinct types of B-cells can be distinguished and quantified at the ultrastructural level.9,10 Ultrastructural analysis of of the light and dark zones in tonsils shows that FDC subtypes can be recognized representing distinct differentiation stages of FDC (Rademakers and Schuurman, this issue). We applied this approach to GCs in lymph nodes of HIV-1 infected patients to analyze alterations in the GC microenvironment.KeywordsGerminal CentreFollicular Dendritic CellDark ZoneLight ZoneFollicular Hyperplasia