Human Leukocyte Antigen Typing with Sequence Specific Oligonucleotides for Renal Transplantation in South Africa.

BACKGROUND: Kidney transplants are the only curative therapeutic intervention for end-stage kidney disease (ESKD). The current organ shortage in South Africa makes recipient risk assessments and effective laboratory workup crucial to assist in better organ assignment and increase the likelihood of better transplant outcomes. HLA typing is a step in the pre-transplant workup for performing virtual crossmatches and matching donors and recipients. Sequence Specific Oligonucleotide (SSO) PCR is a relatively fast and inexpensive method for determining genotypic HLA types at a 2- to 4-digit resolution. This study aimed to validate the SSO technique for achieving a 4-digit resolution when determining HLA types to improve virtual crossmatches. METHODS: DNA was extracted from 33 samples. After PCR amplification, the samples were hybridized to oligonu-cleotide probes and the HLA A, B, C, DRB1, DQA1/B1, DRB3, DRB4, DRB5, and DPA1/B1 types were identified. These results were compared to results from external laboratories. RESULTS: The kappa coefficient calculated for the low-resolution comparison suggested a perfect agreement between the two results (p = 0.32). CONCLUSIONS: SSO was successfully validated for HLA typing in the Johannesburg kidney transplant setting. This will improve the specificity of virtual crossmatches on an automated system by matching the resolution of the HLA typing and the HLA antibody testing. Additionally, common HLA types were identified in this donor cohort. Future research into these common HLA types and haplotypes in a South African population will inform the feasibility of reintroducing HLA matching into the pretransplant workup.

Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa.

Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa's fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69-70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08-0.09) and 0.10 (95% CI: 0.09-0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.