新疆经典型卡波氏肉瘤患者不同样本HHV-8DNA病毒载量与临床分期关系初步分析

目的：了解新疆经典型卡波氏肉瘤（Kapos’s sarcoma，KS）患者皮损、外周血单核细胞（peripheral blood mono—nuclear cells，PBMC）、唾液和尿液中人疱疹病毒型（HHV8）DNA病毒载量水平及分布情况，探讨HHV8病毒载量与经典型KS临床分期之间的相关性。方法：选取2011-03-09-2012-11-11就诊于新疆医科大学第一附属医院皮肤科8例经典型KS患者的4种类型32份样本中扩增HHV8DNAORF26基因片段，应用RrqPCR测定32份样本中HHV8病毒载量，评价栽量负荷与经典型KS疾病临床分期之间的关系。结果：全部资料均获完整基因组DNA。新疆经典型KS患者不同样本中HHV8DNA检出率为100％。标准曲线良好，扩增产物特异，其中，HHV8病毒载量负荷皮损组织为205．75±124．02，唾液为70．75±53．01，PBMC为39．88±26．98，尿液为28．25±12．26，差异有统计学意义，F=11．206，P〈0．001。HHV8病毒载量水平皮损组织〉唾液〉PBMC〉尿液。结论：新疆经典型Ks患者多样本中均有HHV8DNA检出，HHV8病毒载量水平在皮损中最高，在尿液中最低，与新疆经典型KS临床分期之间未呈现相关性趋势。     

Monoclonality or oligoclonality of human herpesvirus 8 terminal repeat sequences in Kaposi's sarcoma and other diseases

BACKGROUND: Infection with human herpesvirus 8 (HHV8), also termed Kaposi's sarcoma (KS)-associated herpesvirus, is associated with all forms of KS, with primary effusion lymphoma (PEL), and with some forms of multicentric Castleman's disease (MCD), but the pathogenic role of HHV8 in these tumors and the clonal nature of KS are still unclear. The purpose of this study was to examine whether the number of terminal repeats (TRs) contained in the fused TR region of HHV8 could be used as a marker of clonality in HHV8-associated tumors. METHODS: Pulsed-field gel electrophoresis (PFGE) and multiple-probe Southern blot analysis of the HHV8 TR region were performed on high-molecular-weight DNA obtained from tumoral KS, PEL, and MCD lesions. RESULTS: These analysis showed that the fused TR region contains a large but variable number of TR units (ranging from 16 to 75) and that the viral genome is present as extrachromosomal circular DNA in these tumors in vivo, with occasional ladders of heterogeneous linear termini reflecting lytic replication. All PEL tumors and PEL-derived cell lines as well as some KS tumors contained monoclonal or oligoclonal fused TR fragments; however, the TR region appeared polyclonal in MCD tumors and in a few KS lesions. CONCLUSION: Several KS and PEL lesions are monoclonal expansions of a single infected cell, suggesting that HHV8 infection precedes tumor growth and thus supporting an etiologic role of latent HHV8 in these proliferations. Our finding that nodular KS lesions display all possible patterns of clonality supports the model according to which KS begins as a polyclonal disease with subsequent evolution to a monoclonal process.     

Kaposi’s sarcoma: Clinico-pathological analysis of human immunodeficiency virus (HIV) and non-HIV associated cases

Kaposi s sarcoma (KS) is a angioformative lesion that classically occurs in elderly Eastern European and Mediterranean males but is also common in immunosuppressed individuals particularly human immunodeficiency virus (HIV)-infected patients. This study investigates the clinical and histopathological features of 47 patients with Kaposi s sarcoma from a teaching hospital in Sydney, Australia, in which 44 cases had adequate clinical follow-up information over a 10-year period. Most of the lesions were of late stage (37/47 cases; 79%), consisting of 11 cases of plaque stage KS and 26 cases of nodular stage KS with only 10 cases of early or patch stage KS. The majority of the HIV-positive cases (23/33; 70%) and all of the HIV-negative (14/14; 100%) cases had late stage lesions (p=0.020; X 2 -test). The histopathological features that were more common in the KS lesions of HIV-negative patients were lesional cell mitosis (p=0.0002), single cell necrosis (p=0.001), apoptosis (p=0.0001) and single cell anaplasia (p=0.0001). The KS lesions in HIV-positive patients tended to have dissecting blood vessels (14/33 cases; 42%) unlike those seen in HIV-negative patients (0/14 cases; 0%) (p=0.004). Most HIV-positive cases (30/33; 90%) were males (p=0.0068); and all these patients (33/33 cases; 100%) were <60 years old, in contrast to HIV-negative patients (1/11 cases; 9%) (p=0.0001). HIV status does not affect the occurrence of multiplicity of KS lesions. However, extracutaneous or visceral KS lesions were more likely to occur in HIV-positive patients (p=0.027). The number of cases of histologically proven KS cases has decreased markedly over the recent 5 year period of 1995-1999 (n=14), which was less than half of the number of the preceding 5 year period, 1990-1994 (n=33). In summary, there are distinct differences in the clinical and histopathological features of Kaposi s sarcoma lesions in HIV-positive and HIV-negative patients. Despite the recent discovery of the HHV8 virus as the initiating and promoting factor of most of the KS lesions, these differences indicated that there might be different mechanisms that occur in HIV-positive and HIV-negative patients in the development of this lesion.     

Is human herpesvirus 8 infection more common in men than in women? Systematic review and meta‐analysis

All forms of Kaposi sarcoma (KS) are more common in men than in women. It is unknown if this is due to a higher prevalence of human herpesvirus 8 (HHV‐8), the underlying cause of KS, in men compared to women. We did a systematic review and meta‐analysis to examine the association between HHV‐8 seropositivity and gender in the general population. Studies in selected populations like for example, blood donors, hospital patients and men who have sex with men were excluded. We searched Medline and Embase from January 1994 to February 2015. We included observational studies that recruited participants from the general population and reported HHV‐8 seroprevalence for men and women or boys and girls. We used random‐effects meta‐analysis to pool odds ratios (OR) of the association between HHV‐8 and gender. We used meta‐regression to identify effect modifiers, including age, geographical region and type of HHV‐8 antibody test. We included 22 studies, with 36,175 participants. Men from sub‐Saharan Africa (SSA) [OR 1.21, 95% confidence interval (CI) 1.09–1.34], but not men from elsewhere (OR 0.94, 95% CI 0.83–1.06), were more likely to be HHV‐8 seropositive than women (p value for interaction = 0.010). There was no difference in HHV‐8 seroprevalence between boys and girls from SSA (OR 0.90, 95% CI 0.72–1.13). The type of HHV‐8 assay did not affect the overall results. A higher HHV‐8 seroprevalence in men than women in SSA may partially explain why men have a higher KS risk in this region.     

Seroprevalence of Human herpesvirus 8 (HHV-8) and incidence of Kaposi's sarcoma in Iran

Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8) infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%), renal transplant recipients (25%) and HIV (45.7%) patients compared to blood donors (2%). Kaposi's sarcoma (KS) is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.     

Human herpesvirus 8 seropositivity and risk of Kaposi's sarcoma and other acquired immunodeficiency syndrome-related diseases.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) is increased severalfold in individuals infected with human immunodeficiency virus-1 (HIV). Human herpesvirus 8 (HHV8) has also been implicated in KS. We investigated several factors that may determine the onset of KS, particularly HHV8 infection in individuals after becoming seropositive for HIV. METHODS: We studied 366 individuals belonging to different HIV-exposure categories (i.e., homosexual activity, intravenous drug use, and heterosexual contact) for whom a negative HIV serologic test and then a positive HIV serologic test were available within a 2-year period. HHV8 antibody testing was performed by use of an immunofluorescence assay on the first serum sample available after the first positive HIV test. Actuarial rates of progression of KS and of other acquired immunodeficiency syndrome (AIDS)-defining diseases were estimated by use of time-to-event statistical methods. All statistical tests were two-sided. RESULTS: Twenty-one of the 366 study participants developed AIDS-related KS, and 83 developed AIDS without KS. One hundred forty (38.3%) participants had detectable anti-HHV8 antibodies. The actuarial progression rate to KS among persons co-infected with HIV/HHV8 was nearly 30% by 10 years after HIV seroconversion. Increasing HHV8 antibody titers increased the risk of developing KS (for seronegative versus highest titer [1:125 serum dilution], adjusted relative hazard [RH] = 51.82; 95% confidence interval [CI] = 6.08-441.33) but not of other AIDS-defining diseases (adjusted RH = 1.14; 95% CI = 0.72-1.80). HHV8-seropositive homosexual men compared with HHV8-seropositive participants from other HIV-exposure categories showed an increased risk of KS that approached statistical significance (adjusted RH = 6.93; 95% CI = 0.88-54.84). CONCLUSIONS: Approximately one third of individuals co-infected with HIV/HHV8 developed KS within 10 years after HIV seroconversion. Progression to KS increased with time after HIV seroconversion. Higher antibody titers to HHV8 appear to be related to faster progression to KS but not to other AIDS-defining diseases.     

Clinical aspects and management of AIDS-related Kaposi's sarcoma

AIDS-related Kaposi's sarcoma (KS) is a tumour of vascular endothelium, which is seen predominately in men who have sex with men. The majority of affected individuals have advanced immunosuppression at the time of the initial KS diagnosis. The disease may present with cutaneous lesions, or with involvement of visceral organs, of which the gastrointestinal tract is most common. KS may also present with lymphoadenopathy or with isolated lymphoedema, even in the absence of cutaneous lesions. Affected individuals are uniformly co-infected with HIV and with Human Herpesvirus type 8 (HHV8). HHV8 is present within KS tissues, and is aetiological in the pathogenesis of disease, along with aberrant cytokine expression, production of multiple angiogenic peptides, and immune dysregulation. While not presently curable, multiple treatment options exist and must be evaluated in terms of the specific needs of the individual patient. Various local therapies are aimed at eradicating small lesions, while acknowledging that the KS in general, or its likelihood of recurring will be unaffected. Systemic chemotherapy is used to treat extensive visceral involvement. Knowledge of the pathogenesis of disease has led to the development of novel treatment strategies, aimed at HHV8 as the target of therapy, or at the inflammatory cytokine or angiogenic milieu necessary for KS growth. Use of highly active anti-retroviral therapy, aimed at controlling the underlying HIV infection, has been associated with a dramatic decrease in the incidence of KS, and may also be useful in the treatment of existing KS disease.     

Herpesvirus-like DNA sequences detected in endemic,classic, iatrogenic and epidemic Kaposi's sarcoma (KS) biopsies

The identification of Kaposi's sarcoma (KS) clusters in subequatorial Africa (endemic KS, AKS) and the high frequency of KS in sexually transmitted AIDS (epidemic KS, EKS), have previously suggested a role for infectious agents in the etiopathogenesis of KS. The recent identification of herpesvirus (HHV)-like DNA sequences in one case of EKS and their detection in >90% of all tested EKS, prompted us to determine the prevalence of these viral sequences in all types of KS, such as AKS, EKS, classic KS (CKS) and iatrogenic KS (IKS). The presence of herpesvirus (HHV)-like DNA sequences has been examined in 61 KS skin tumors obtained from Greece, Italy, USA, Uganda and Kenya. All KS types (100%) were positive by polymerase chain reaction (PCR) and Southern-blot analysis, while 5 out of 6 (83%) and 4 out of 7 (57%) uninvolved autologous skin biopsies from AKS and CKS patients, respectively, were positive for HHV-like sequences. All samples from non-KS patients were negative, i.e. 17 human biopsies from healthy individuals or patients affected by other pathologies, 5 human cell lines and 15 peripheral blood mononuclear cells (PBMC) from HIV-positive subjects. These results suggest that HHV-like sequences play a major role in the pathogenesis of this neoplasm. © 1996 Wiley-Liss, Inc.     

Clinical Effectiveness of Preoperative Embolization for Cerebellar Hemangioblastoma

The cerebellar hemangioblastoma (CHB) has an abundant blood supply and deep anatomical location.Complete surgical resection is generally very difficult. This study investigated the safety and effectiveness ofpreoperative embolization followed by surgical resection of CHB in a large cohort of patients. A database of 125CHB patients with surgical resection in Beijing Tiantan Hospital between July 2006 and July 2012 was reviewed.Of those, 46 cases (experimental group) received preoperative embolization, 79 cases (control group) underwentsurgery without embolization. Patient demographics, tumor size, duration of surgery, blood loss, blood transfusion,complications and follow-up results were collected and analyzed retrospectively. In the experimental group, theKamofsky score (KS) was 80-100 in 40 cases (86.9%), 40-70 in 4 cases (8.7%), and below 40 in 2 cases (4.3%).Among 31 cases with follow-up, KS was 80-100 in 27 cases (87.1%), 40-70 in 2 cases (6.5%), and 0 in 2 cases(6.5%). In control group, KS was 80 -100 in 65 cases (82.2%), 40-70 in 6 cases (7.6%), 10-30 in 3 cases (3.8%),and 0 in 3 cases (3.8%). Among 53 cases with follow-up, KS was 80-100 in 44 cases (83.0%), 40-70 in 4 cases(7.5%), 10-30 in 1 case (1.9%), and 0 in 4 cases (7.5%). There were statistically significant differences betweenthe experimental and control groups in tumor size, duration of surgery, amount of intraoperative blood loss andtransfusion (p <0.01). However, complications (p = 0.31) and follow-up results (p = 0.76) showed no significantdifferences between groups. Selective preoperative embolization of those CHB patients with richer blood supply,higher hemorrhage risk, is safe and effective, and is a reliable adjuvant therapy for complete surgical resectionof CHB.     

High titers of anti-human herpesvirus 8 antibodies in elderly males in an endemic population

Human herpesvirus 8 (HHV8) is the etiologic agent of Kaposi's sarcoma (KS), a tumor occurring mainly among elderly men in its endemic and classical forms. The male-to-female ratio of KS in different endemic populations ranges from 3 : 1 to 15 : 1. We investigated the influence of age and gender on anti-HHV8 antibody titers among HHV8-seropositive subjects of an endemic population (1819 villagers with 874 men and 945 women) of African origin living in French Guiana. By using a specific immunofluorescence assay, we found that the overall HHV8 seroprevalence of antibodies against lytic antigens was 11.8%. There was no difference between seroprevalence in males (11.7%) and females (11.8%). Among the 214 HHV8-seropositive subjects, anti-HHV8 antibody titers were found to increase with age (P<.001) and were higher in males than in females (P =.003). The geometric mean of HHV8 antibody titers was 1 : 105 (95% confidence interval [CI] = 1 : 77 to 1 : 144) for males versus 1 : 62 (95% CI = 1 : 47 to 1 : 81) for females. The titers increased from 1 : 59 (95% CI = 1 : 43 to 1 : 80) in males younger than 40 years to 1 : 452 (95% CI = 1 : 244 to 1 : 839) in the oldest male group (aged 50 years and older). Such high antibody titers directed against lytic antigens in males aged 40 years and older parallel the increase of endemic KS incidence in older African men. Our results suggest that the role of gender should also be considered in evaluating the association between anti-HHV8 antibody titers in people aged 40 years and older and the risk of developing KS.     

Classic kaposi sarcoma: epidemiology and risk factors

BACKGROUND: Although Kaposi sarcoma (KS) initially was described over a century ago, its biology remains enigmatic and conflicting. Whereas the classic type occurs mainly in older men of Mediterranean or Eastern European backgrounds and is not linked to impairment of the host immune response, iatrogenic and human immunodeficiency virus (HIV)-associated KS are linked to such conditions. A recently discovered pathogen, KS-associated herpesvirus (KSHV) (also known as human herpesvirus 8 [HHV8]), is found in tissues from all four forms of KS (classic, iatrogenic, endemic [African], and HIV-associated). This universal detection of KSHV/HHV8 suggests a central role for the virus in the development of KS and a common etiology for all KS types. The epidemiology and risk factors of classic KS, along with the biology of KSHV/HHV8 and the prevalence of the virus among different populations, is presented. METHODS: The current review is based on multiple information sources, electronic health data in all languages from 1966 onward, and previously published scientific reports from the Americas, Europe, and Africa. RESULTS: Nearly 5000 cases of morphologically characterized classic KS have been reported in Europe, Mediterranean countries, and the Americas up to 1998. Geographic location, ethnicity, time interval, age, and gender heavily influence the incidence rate of classic KS. The rate of incidence of nonacquired immunodeficiency syndrome-associated KS correlates with the KSHV/HHV8 seroprevalence in the general population. CONCLUSIONS: Many contributory factors undoubtedly have etiologic and pathogenic significance in the development of classic KS; however, the interplay between these factors has complicated the understanding of the induction and development of the disease as well as the significance of each factor. As with other cell-transforming human DNA viruses, infection with KSHV/HHV8 alone is not sufficient for the development of KS and additional cofactors are required.     

Angiopoietin-like 4: a novel molecular hallmark in oral Kaposi's sarcoma

Kaposi's sarcoma (KS) remains among the most common causes of oral cancer in HIV-infected individuals. Infection with the KS-associated herpesvirus (KSHV/HHV8) is a necessary event for disease development. Emerging evidence suggests that KSHV infects vascular endothelial (or endothelial progenitor) cells promoting the formation of the KS tumor (or spindle) cell. These cells elaborate angiogenic growth factors and cytokines that promote the dysregulated angiogenesis and profuse edema that characterizes this unusual vascular tumor. Central among these secreted factors is the potent endothelial cell mitogen, vascular endothelial growth factor (VEGF). Indeed, VEGF has proven to be a key player in KSHV pathogenesis and is a molecular hallmark of KS lesions. We have recently shown that a second angiogenic factor, Angiopoietin-like 4 (ANGPTL4), may also play a critical role in KS development. Here we demonstrate that ANGPTL4 is upregulated both directly and indirectly by the KSHV oncogene, vGPCR. We further show that ANGPTL4 is a molecular hallmark of oral KS lesions. Indeed, expression of this protein was observed in more tumor cells and in more biopsies specimens than expression of VEGF (23/25 or 92% vs. 19/25 or 76%, respectively) in oral KS. These surprising results support a key role for ANGPTL4 in Kaposi's sarcomagenesis and further suggest that this angiogenic factor may provide a novel diagnostic and therapeutic marker for oral KS patients.     

Does Kaposi’s sarcoma predict multicentric Castleman disease in the presence of generalized lymphadenopathy?

Multisystemic Castleman disease (MCD) can be associated with HHV8 infection, which involves the mantle zone of follicles. This condition results in an increase number of HHV8-positive (HHV8+) plasmablasts that multiply and amalgamate to form plasmablastic B-cell lymphoma. All previously reported cases of HIV-positive patients with MCD were coinfected with HHV8. Twelve cases of HIV- MCD that are HHV8+ were encountered in the literature, three of them developed lymphoma, and none of those cases were reported to have Kaposi's sarcoma (KS). We report a unique case of HIV-negative elderly woman with preexisting KS that presented to the hospital with recurring nausea, vomiting, and fever, assessment revealed diffuse lymphadenopathy. Axillary lymph node biopsy showed HHV8+ MCD with foci of microlymphoma. Despite the treatment with high-dose steroids, she developed multisystem failure that lead to her death.     

Substantial regional differences in human herpesvirus 8 seroprevalence in sub‐Saharan Africa: Insights on the origin of the “Kaposi's sarcoma belt”

Equatorial Africa has among the highest incidences of Kaposi's sarcoma (KS) in the world, thus earning the name “KS Belt.” This was the case even before the HIV epidemic. To date, there is no clear evidence that HHV‐8 seroprevalence is higher in this region but interpretation of the available literature is tempered by differences in serologic assays used across studies. We examined representatively sampled ambulatory adults in Uganda, which is in the “KS Belt,” and in Zimbabwe and South Africa which are outside the Belt, for HHV‐8 antibodies. All serologic assays were uniformly performed in the same reference laboratory by the same personnel. In the base‐case serologic algorithm, seropositivity was defined by reactivity in an immunofluorescence assay or in 2 enzyme immunoassays. A total of 2,375 participants were examined. In Uganda, HHV‐8 seroprevalence was high early in adulthood (35.5% by age 21) without significant change thereafter. In contrast, HHV‐8 seroprevalence early in adulthood was lower in Zimbabwe and South Africa (13.7 and 10.8%, respectively) but increased with age. After age adjustment, Ugandans had 3.24‐fold greater odds of being HHV‐8 infected than South Africans (p < 0.001) and 2.22‐fold greater odds than Zimbabweans (p < 0.001). Inferences were unchanged using all other serologic algorithms evaluated. In conclusion, HHV‐8 infection is substantially more common in Uganda than in Zimbabwe and South Africa. These findings help to explain the high KS incidence in the “KS Belt” and underscore the importance of a uniform approach to HHV‐8 antibody testing.     

HIV and human herpesvirus 8 co‐infection across the globe: Systematic review and meta‐analysis

HIV‐infection is an important risk factor for developing Kaposi sarcoma (KS), but it is unclear whether HIV‐positive persons are also at increased risk of co‐infection with human herpesvirus 8 (HHV‐8), the infectious cause of KS. We systematically searched literature up to December 2012 and included studies reporting HHV‐8 seroprevalence for HIV‐positive and HIV‐negative persons. We used random‐effects meta‐analysis to combine odds ratios (ORs) of the association between HIV and HHV‐8 seropositivity and conducted random‐effects meta‐regression to identify sources of heterogeneity. We included 93 studies with 58,357 participants from 32 countries in sub‐Saharan Africa, North and South America, Europe, Asia, and Australia. Overall, HIV‐positive persons were more likely to be HHV‐8 seropositive than HIV‐negative persons (OR 1.99, 95% confidence interval [CI] 1.70–2.34) with considerable heterogeneity among studies (I² 84%). The association was strongest in men who have sex with men (MSM, OR 3.95, 95% CI 2.92–5.35), patients with hemophilia (OR 3.11, 95% CI 1.19–8.11), and children (OR 2.45, 95% CI 1.58–3.81), but weaker in heterosexuals who engage in low‐risk (OR 1.42, 95% CI 1.16–1.74) or high‐risk sexual behavior (OR 1.66, 95% CI 1.27–2.17), persons who inject drugs (OR 1.66, 95% CI 1.28–2.14), and pregnant women (OR 1.68, 95% CI 1.15–2.47), p value for interaction <0.001. In conclusion, HIV‐infection was associated with an increased HHV‐8 seroprevalence in all population groups examined. A better understanding of HHV‐8 transmission in different age and behavioral groups is needed to develop strategies to prevent HHV‐8 transmission.     

The role of immunosuppression and immune-activation in classic Kaposi's sarcoma.

Immunodeficiency and elevated levels of cytokines have been associated with the development of Kaposi's sarcoma (KS) lesions in patients with AIDS and iatrogenic immunodeficiency. However, their role in classic KS (CKS) is unclear. We measured peripheral blood cell levels, including T-cell subsets, as well as neopterin and beta(2)-microglobulin in 91 HIV-negative Greek patients with histologically confirmed CKS and in 107 controls matched for age and sex. CKS cases had slightly lower leukocyte counts (p = 0.08) and lymphocyte counts (p = 0.02). Although the percentage of CD4 and CD8 T-lymphocytes were not significantly different from controls (p = 0.10 and p = 0.45, respectively), CD4 T-lymphocytes were lower in cases than controls (812 cells/microliter and 1,009 cells/microliter, respectively; p = 0.01); part of this difference resulted from the lower lymphocyte counts (p = 0.07 after adjusting for lymphocyte counts). However, neopterin and beta(2)-microglobulin were both considerably elevated [geometric mean (95% CI): 8.35 (7.27-9.73) nmol/L and 2,904 (2,479-3,401) microgram/L in cases and 5.86 (5.40-6. 35) nmol/L and 2,042 (1,880-2,218) microgram/L in controls, respectively]. We conclude that CKS patients are predominantly characterised by immune activation, although an element of minor immunosupression may also be present.     

Biology of Kaposi's sarcoma

Kaposi's sarcoma (KS) is an angioproliferative disease occurring in several different clinical-epidemiological forms that, however, share the same histological traits and are all associated with infection by the human herpesvirus 8 (HHV8). KS initiates in a context of immune dysregulation characterised by CD8+ T cell activation and the production of Th1-type cytokines that induce a generalised activation of endothelial cells leading to adhesion and tissue extravasation of lympho-monocytes, spindle cell formation and angiogenesis. These phenomena are triggered or enhanced by infection with HHV8 that, in turn, is reactivated by the same cytokines. Productively-infected circulating cells are recruited into ‘activated’ tissue sites where HHV8 finds an optimal environment for establishing a persistent, latent infection of KS spindle cells (KSC). HHV8 dissemination is favoured by virus escape mechanisms and immune dysregulation, and leads to immune responses that are not effective against the virus but, paradoxically, exacerbates the reactive process. Although early KS is a reactive process of polyclonal nature that can regress, in time it can progress in to a true sarcoma. The progression of KS appears to be due to the deregulated expression of oncogenes and oncosuppressor genes, to the long-lasting expression of the HHV8 latency genes and, for AIDS-KS, is promoted by the proliferative and angiogenic effects of the HIV-1 Tat protein.