Faculty of Health Sciences
School of Medicine
Department of Immunology
Selected Highlights from Research Findings
The researchers evaluated the feasibility of the oligonucleotide ligation assay (OLA), a specific, sensitive and economical ligase-based point mutation assay designed to detect HIV-1 drug-resistance mutations at 12 codons of HIV-1 subtype B pol, for potential use in resource-poor settings. Specimens from HIV-1-infected individuals collected by seven international laboratories, including subtypes A, B, C, D, F, G, J and recombinants AE and AG, were tested by the OLA developed for HIV-1 subtype B. Common polymorphisms that interfered with reactivity of the OLA were identified, and modified probes designed and evaluated. The researchers successfully genotyped 92.5% (2 410) of 2 604 codons in specimens from 217 individuals. A high rate (range 8.3% to 31.2%) of indeterminate results (negative OLA reaction for both mutant and wild type) was observed for five codons. Modified probes at reverse transcriptase codons 151 and 184 and protease codon 90 increased the rate of valid OLA to 96.1%. The researchers found that the OLA designed for HIV-1 subtype B genotyped most pol codons in non-B subtypes from Asia and Africa, but was improved by the addition of several modified probes. International laboratories experienced in molecular techniques were able to perform the OLA
Contact person: Prof SA Cassol.
The aim of this study was to provide a detailed description of the clinical, virological and immunological characteristics of AIDS/Kaposi's Sarcoma (KS), an associated herpes virus in men and women who are not making use of antiretroviral therapy (ART). The study also measured the extent of KS disease directly (level of cutaneous and visceral involvement), rather than relying on the reporting of non-specific symptoms such as fever, diaphoresis and weight loss. The proportion of women with HIV-1-related KS (ratio of 1:1) was substantially higher than that reported for American, European and other African population groups. One of the reasons for this might be the fact that the prevalence and incidence of HIV-1 in KwaZulu-Natal are among the highest in sub-Saharan Africa, with young women bearing the major impact of the burden. The researchers found that AIDS/KS is unequally distributed among different age groups and that the proportion of AIDS/KS cases was highest among women in their mid-20s. Also of considerable interest was the finding that the age-specific distribution pattern for female KS was essentially identical to that previously reported for HIV-1 on its own. In past studies conducted in KwaZulu-Natal, the prevalence (and incidence) of HIV-1 increased in young mothers between the ages of 21 and 25, and then levelled off and declined in women 30 years of age. Taken together, this data suggests that the risk of developing female KS, at least in KwaZulu-Natal, is closely related to the epidemiology (and/or transmission) patterns of HIV-1. The finding that, at diagnosis, women had more extensive KS disease is consistent with studies from Zimbabwe and Italy showing that women with AIDS/KS are more symptomatic, have more advanced disease, and a more aggressive clinical presentation and disease course relative to men. The reason for the increased severity of KS in HIV-1-infected women is not known, but does not appear to be related to virological or immunological differences since the men and women in the study had similar mean viral load and mean CD4þ T-cell counts. The lack of a gender-related correlation between disease severity and CD4þ T-cell count is in agreement with the Zimbabwean study, but at variance with the data from Italy. Italian investigators found that, relative to men, women with KS were more immune deficient. Despite the lack of a difference between men and women, the researchers found that in each gender group, there was a statistically significant relationship between lower CD4þ T-cell counts and more advanced KS disease, and between lower CD4þ T-cell counts and poor disease prognosis, suggesting that immune suppression may play a role in KS progression, but that this role may not necessarily be related to gender. The wide variation in CD4þ T-cell counts observed in this study (from 1 to 1 406 cells/mm3) and the finding that 21% of patients had CD4þ T-cell levels .350 cells/mm3 (38% .200 cells/mm3) suggests that, in African populations, severe immune suppression is not a prerequisite for the development of KS lesions. Although the reasons are not known, higher than expected CD4þ T-cell counts in African patients had been reported previously. In the African setting, great care must be taken to accurately diagnose and differentiate between KS- and tuberculosis-induced pulmonary diseases. Given that tuberculosis may coexist with AIDS/KS in 20% of patients, and that the diagnosis of this condition may influence both the timing and choice of ART, it is recommended that all AIDS/KS patients receive a clinical evaluation and sputum examination for the detection of acid-fast bacilli, and that those with symptomatic lung disease be ruled out for tuberculosis
Contact person: Prof SA Cassol.
Canova is an immunomodulatory, homeopathic preparation that has been shown to activate macrophages in vitro and in vivo, with resultant enhanced spreading of the cells and formation of microvillus extensions from the cell body. Since monocytes are the precursor cells of macrophages and dendritic cells, the objective of this study was to investigate the effects of Canova on the differentiation of human blood monocytes in vitro. Monocytes were isolated, grown in culture and exposed to 10 and 20% Canova without the addition of cytokines. After 48 hours, monocytes were prepared for analysis by scanning electron microscopy, while cells kept in culture for seven days and exposed to Canova on days one, three and four were analysed by flow cytometry for alterations in the levels of expression of CD1a, CD11c, CD14, CD80, CD83, CD86 and HLA-DR. Scanning electron microscopy revealed that monocytes exposed to 10% Canova had a morphological appearance similar to that of macrophages. Various cytoplasmic projections were observed with pseudopodia formation. Flow cytometric analysis after exposure of monocytes to 10 and 20% Canova indicated high cell viability and upregulation of CD80, compatible with differentiation into either macrophages or dendritic cells. Exposure to Canova per se causes activation of monocytes with resultant differentiation into large macrophage-like cells of indeterminate phenotype that have increased expression of CD80. Like cytokines, Canova induces differentiation of monocytes, an activity that may underpin the immunomodulatory activity of this product
Contact person: Prof R Anderson.
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