This study was conducted to investigate the role of natural killer cell surface receptors, KIRs and their cognate HLA ligands in preventing HIV-1 acquisition and disease progression in HIV-1 exposed infants. Using DBS stored for 8 years from 21 pregnant South African women we evaluated 3 methods of gDNA extraction with and without whole genome amplification (WGA) to characterize immune-related genes: IL-10, KIR and HLA class I. However, IL-10 SNP typing was only for testing the quality of gDNA. QIAamp DNA mini kit yielded the highest gDNA quality (p<0.05; Wilcoxon Signed Rank Test) with sufficient yield for subsequent analyses. In contrast, WGA was not reliable for SSP-PCR analysis of KIR2DL1, KIR2DS1, KIR2DL5, and KIR2DL3 or high resolution HLA genotyping using a sequence-based approach. A cohort of 370 infants; 124 HIV-1 perinatally infected, 120 exposed uninfected and 126 unexposed healthy infants was used for KIR and HLA genotyping. After adjustment for viral load and multiple comparisons, the frequency of HLA-Cw*04:01 allele was likely to be associated with susceptibility to mother-to-child acquisition of HIV-1 in exposed infected (EI) infants (p=0.05; Logistic Regression analysis). HLA-A*23:01 was likely to be associated with decreased CD4 T lymphocyte count in HIV-1 infected infants (p=0.01; ANOVA), whereas HLA-B*81 tended to be associated with higher CD4 T lymphocyte count (p=0.04, ANOVA). We speculate that HLA-Cw*04:01 interacts with KIR2DL1 and inhibit NK cell responses which predispose the infants to HIV-1 infection. KIR2DS1 and KIR2DL5 were both associated with faster HIV-1 disease progression. Identified protective HLA-class I alleles could be used to present viral epitopes to either NK cells via KIRs or CTLs and enhance immune activation which may promote resistance to HIV-1 infection. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2012.

The most useful drugs in the management of nephrotic syndrome are the corticosteroids. These drugs are as well known for their adverse effects as they are for their therapeutic advantages. The two most common paediatric side effects are suppression of linear growth and posterior subcapsular cataracts. Both of these untoward effects are insiduous and therefore less easily perceived. Although many workers have studied the growth inhibiting effects of the corticosteroids in the various diseases e.g. asthma, very little work was done to investigate these effects in patients with nephrotic syndrome. Furthermore, the Renal Clinic, King Edward VIII Hospital, Durban continues to use a daily regime of prednisone instead of the alternate day regime which is widely recommended to minimise growth retardation. This study was therefore undertaken to investigate the growth inhibiting effects of repeated courses of daily, high-dose prednisone in African and Indian children with nephrotic syndrome. All children with nephrotic syndrome with relevant data in their records and with no other chronic illness were selected from the Renal Clinic. Of the 125 selected, 87 children had been treated with prednisone for an average of 35,9 weeks and 38 had been treated symptomatically. The heights of those that received prednisone were measured at an averace of 77 weeks after completion of therapy. The mean height standard deviation score (SDS) of the treatment and control groups of Indian children were -1,06 and -0,92 respectively, both being between the 10th and 25th percentile, whilst the mean height SDS of the treatment and control groups of African children were -1,82 (just below the 5th percentile) and -1,77 (between the 5th and 10th percentile) respectively. From the results, it is evident that repeated courses of daily prednisone therapy, even when it exceeds 36 weeks, does not inhibit growth in both African and Indian children. Although there was no significant difference between the races and sexes with respect to growth and corticosteroid therapy, this study does confirm earlier reports that most of the African children with nephrotic syndrome had obvious glomerular lesions whilst most of the Indians had minimal change nephrotic syndrome. / Thesis (M.Med.)-University of Natal, Durban, 1986.