Two novel HLA alleles, HLA-A*30:02:01:03 and HLA-C*08:113, identified in a South African bone marrow donor.

Genomic sequencing of HLA-A*30:02:01:03, an intronic variant, and HLA-C*08:113, an exonic variant.

Polymorphism of DRw52 and its association with DRw11 and DRw12 in South African blacks (Negroes) and individuals of mixed ancestry (Cape coloreds).

The HLA-DRB3 gene, which encodes the supertypic HLA-DRw52 antigen, has been shown to have limited polymorphism. The alleles at this locus are also in linkage disequilibrium with the alleles at the DRB1 locus. We have studied 16 DRw11 and three DRw12 haplotypes in the South African populations. Five of the DRw11,DQw7 haplotypes were associated with a TaqI restriction fragment length polymorphism which has not been previously described and which correlated with the DRB3 gene. This new variant, which has been called DRw52d, is confined to individuals of black or mixed ancestry. Two of the DRw11,DQw7 haplotypes were also associated with DRw52a or DRw52c and not with DRw52b as has always been observed in white populations. The less common DRw11,DQw6 haplotype, observed in four individuals, also revealed different allelic associations with the DRB3 gene, together with an unusual DQA association. None of the three DRw12,DQw7 haplotypes had the usual association with the DRw52b allele and also demonstrated two distinct DQA associations. The pattern of linkage disequilibrium of the HLA-D region loci in the South African black populations is more complex than in other populations. These findings may be of significance for the matching of unrelated donors for organ transplantation, as well as the study of disease association with HLA.

Unusual HLA-DR,DQ haplotypes found in South African families of black, Asian Indian, and mixed ancestral origin.

Four non-Caucasoid families with the unusual HLA-DR,DQ haplotypes DRw17,DQw7; DR9,DQw2; DR4,DQw2; and DR4,DQw5 were studied. All four haplotypes showed identical serological patterns to those seen with the equivalent Caucasoid antigens, but no HLA-Dw specificities could be assigned. TaqI restriction fragment length polymorphism (RFLP) patterns observed using DRB, DQB, and DQA probes showed that the DRw17,DQw7 haplotype may have originated from a homologous crossover between a DRw17,DQw2 haplotype and a haplotype with DQw7. The results obtained for the DR9,DQw2 and DR4,DQw2 haplotypes suggest that these could have resulted from recombination events with an ancestral "black" DQw2 haplotype. From the RFLP data, it is difficult to postulate the origin of the DR4,DQw5 haplotype being from a single recombination event.

The HLA genetic constitution of the Bushmen (San).

The HLA-A, -B, and -C antigens of 290 and the DR antigens of 212 !Kung San individuals were characterized. The most frequent antigens were HLA-A30 [gene frequency (gf) = 0.193], Bw58 (gf = 0.303), Cw6 (gf = 0.327), DR4 (gf = 0.273), and DQw3 (gf = 0.553). An unexpected finding was the low frequency of the classic African black antigen Bw42 (gf = 0.004). Marked differences as well as similarities in HLA gene frequencies were observed between the San and the South African Negroes, supporting the view that they had a common origin and were then separated for a very long time. During this period differences developed as a result of selective advantage in the Negroes following the pastoralist-agriculturalist way of life as opposed to the hunter-gatherer way of life. The picture is further complicated by the fact that gene flow, mostly from the San to the southern African Negroes, took place when they met again a few hundred years ago. The data also illustrate HLA haplotypes, linkage disequilibria, and four-locus haplotypes not previously seen in other human populations. The most frequent four-locus haplotype in the San, HLA-Aw43,Cw7,B7,DRw6 was also different from A30, Cw2,Bw42,DR3, the most common among the South African Negroes.

The polymorphism of HLA-DR3 in South African populations.

The polymorphism of HLA-DR3 was investigated in families and unrelated individuals of three population groups: South African (SA) Negroes, Cape Coloureds and SA Caucasoids. Serological and restriction fragment length polymorphism (RFLP) analysis indicated that DR3 could be subdivided into DRw17 (previously DR3.1) and DRw18 (previously DR3.2). In contrast, the two-dimensional (2-D) gel electrophoresis patterns could not distinguish between the DRB1 gene products of the HLA-DRw17 and DRw18 cells. Two DRB3 variants, correlating with the T-cell defined specificities Dw24 and Dw25 were identified at the genomic and product level. Of ten haplotypes studied with the newly defined HLA-DRw18 specificity, all had the DRB3 RFLP pattern associated with Dw24. HLA-DRw17 was found in all three population groups tested, although in the SA Negroes HLA-DRw18 was the prevalent DR3 subgroup. This subgroup was also present in the Cape Coloureds but was absent in the SA Caucasoids tested. HLA-DRw18 forms part of the most characteristic SA Negro haplotype, Bw42, DQw4, Dw"RSH," while HLA-DRw17 is part of the classic Caucasoid haplotype, B8, DQw2, Dw3.

Restriction fragment length polymorphism of HLA-DRw53 detected in South African blacks and individuals of mixed ancestry.

The HLA-DRw53 specificity has not until now been shown to demonstrate polymorphism. We have studied 33 DRw53 haplotypes, comprising 19 DR4, 10 DR7, and 4 DR9 haplotypes, from 6 homozygous typing cells, 11 families, and 8 random individuals. All the subjects studied were South African blacks or of mixed ancestry (Cape Coloureds), with the exception of four homozygous typing cells from whites. The DNA was digested with TaqI and, after Southern blotting, was hybridized with a full-length DRB cDNA probe. Fragments correlating with DR4 (5.5 kb), DR7 (4.0 kb), and DR9 (4.1 kb) were observed. Two fragments of 14.5 and 2.8 kb correlated with DRw53. In addition, two pairs of fragments demonstrated a diallelic pattern, which is likely to correlate with a polymorphism of the DRB4 (DRw53) gene, since one or other of the two patterns was observed in all cells carrying the DRw53 specificity. The first allelic pattern, called DRw53a, was characterized by the presence of 7.5- and 2.6-kb fragments, while the second pattern, called DRw53b, had 5.8- and 2.7-kb fragments. DRw53a occurred in 10 of the 19 DR4 haplotypes and 7 of the 10 DR7 haplotypes. All three DR9,DQw2 haplotypes were also associated with DRw53a. These findings may have important implications for disease associations and the use of unrelated donors for organ transplantation.

A study of the HLA-Dw determinants and their relationship to DR and DQ antigens in three South African population groups: South African Caucasoids, South African Negroes, and Cape coloureds.

The HLA-Dw specificities of a group of 177 unrelated randomly selected healthy individuals consisting of 67 South African Negroes (Xhosa), 57 Cape Coloureds, and 53 South African Caucasoids were determined. HLA-Dw specificities were determined in a mixed lymphocyte culture test using HTCs. Antigen and gene frequencies as well as the association between HLA-DR, DQ, and Dw were established in three populations. HLA-Dw gene frequencies in the South African Caucasoids agreed with these frequencies in other Caucasoid groups. The HLA-Dw1 frequency was decreased in the Cape Coloureds and South African Negroes compared to the Caucasoids. The gene frequency of Dw3 was low in the South African Negroes in spite of the fact that DR3 is a common DR antigen in this group. A high frequency of Dw 'blank' was observed in the South African Negroes and Cape Coloureds, suggesting the existence of undefined HLA-Dw specificities in these populations. Data concerning the HLA-Dw, DR, and DQ relationships showed that once a certain Dw specificity was associated with a particular DR and DQ antigen, this association remained a fixed entity in the different population groups.

HLA-A, B and DR antigens in renal transplantation. A further report on the Northwestern and MEDUNSA experience.

HLA histocompatibility antigens form part of the basis of immune reactions in transplant immunology. However, controversy surrounds their use in renal allograft organ sharing. Selected HLA-related studies in the transplant programmes of Northwestern Memorial Hospital (NWMH), Chicago, USA, and the Medical University of Southern Africa (MEDUNSA), Pretoria, are presented. In the Northwestern Memorial Hospital experience with 27 recipients of O-mismatches, 48% were mixed leucocyte culture (MLC) compatible (% relative response < 25). Actuarial graft survival rates at yearly intervals up to 5 years were 100%, 100%, 85%, 75%, 75%, compared with 75%, 65%, 65%, 55% and 55% in compatible and incompatible groups, respectively (Breslow P = 0.05 and Mantel-Cox P = 0.11). Creatinine values at yearly intervals up to 5 years were significantly better in the MLC-compatible group (Mann-Whitney U-test P < 0.05). In the MEDUNSA experience with 85 black recipients of poorly HLA-matched renal allografts of the same donor race, actuarial graft survival at yearly intervals up to 5 years was 73%, 68%, 61%, 61% and 57%. The commonest HLA-A, B and DR antigens at MEDUNSA are A30, A9, A2, A10, A28; B17, B12, B42, B8; DR3, DR5 and DR4 (in this order of frequency). The NWMH experience illustrates that HLA-matching improves renal allograft survival in O-mismatches. At MEDUNSA, however, satisfactory results are obtained using kidneys harvested from black donors.

Blood group gene frequencies of four population groups in the western Cape.

Blood group gene frequencies of 4 population groups in the western Cape region of South Africa were determined. The ABO, MNSs, Rhesus, Kell and Duffy blood group systems were studied in 2,094 non-Malay Cape Coloureds, 1,181 South African (SA) Negroes, 506 SA Caucasoids and 115 Cape Malays. The gene frequencies of these 4 population groups together with, for comparative purposes, previously published data on 3 others, namely Johannesburg Coloureds, Khoikhoi and San, were used to measure the genetic distances between them. In addition, multivariate analysis was used in an attempt to clarify whether the 2 coloured and the Cape Malay samples resemble each other, and to demonstrate the relationships between the 7 population groups. Although genetic distance measurements suggest that Johannesburg Coloureds have a greater SA Negro contribution to their gene pool than the Cape Coloureds, the results are in accordance with previous studies suggesting that coloureds in southern Africa form a relatively homogeneous group. The allele frequencies in the Rhesus and Duffy blood group systems suggest that Cape Malays, although similar in some respects to the Cape Coloureds, are a genetically distinct group.

Utilization of iron dextran in recurrent iron deficiency anaemia.

Previously published studies have documented a reduction in the rate at which iron stores laid down by iron dextran therapy can be utilized for haemoglobin synthesis after the acute demands of haemorrhage and phlebotomy. In order to determine if a defect in the mobilization of these stores exists in the face of a chronic stimulus to red cell production, 93 patients who had previously received a total dose infusion of iron dextran were examined for a recurrence of iron deficiency anaemia, and in those in whom anaemia had recurred, iron stores were assessed by marrow aspiration. Twenty of the 93 patients were found to have recurrent iron deficiency anaemia, and marrow aspiration in all failed to demonstrate stainable iron stores. Although the rate at which iron dextran can be mobilized from storage sites is reduced, the present study demonstrates that ultimately these stores are fully utilizable.

Folic acid -- has it a role in the treatment of severe iron deficiency anaemia in pregnancy?

Forty-one pregnant patients with severe iron deficiency anaemia were treated with either intravenous iron-dextran (Imferon; Fisons) or intravenous iron plus folic acid. There was no difference in the rate of response or the eventual total response in the two groups, suggesting that iron therapy does not unmask or produce a relative folic acid deficiency.

C4 polymorphism and extended HLA haplotypes in Namibian San and Khoi and in South African Xhosa.

We studied C4A and C4B polymorphisms and HLA-B and -DR associations in the San, Khoi and Xhosa. C4A and C4B alleles were determined using conventional protein allotyping methods. The C4A*3, C4B*1 haplotype had a high frequency (30-55%) in all populations. The frequency of C4A*3, C4B*Q0 was 7-19%. The C4A*Q0, C4B*1 haplotype was frequent (15%) in the Khoi but very rare in the San (P < 0.001). C4A*12 A*91, C4B*Q0 was frequent in the Xhosa (15%) but rare in the San and Khoi (P < 0.001). Alleles C4A*5 and C4A*6, and the C4B*2 B*92 duplication were only found in the Xhosa. C4A alleles A*4, A*45, A*58, A*12, A*14, A*19 and the C4A*3 A*91 duplication were only found in the San/Khoi population group. In the San, fourteen extended haplotypes were found in a relatively high frequency (2-7%). In the Xhosa, one extended haplotype (B42, C4A*12 A*91, C4B*Q0, DR18) was found in a very high frequency (13%) and was characteristic for this group; five other extended haplotypes were found with a low frequency (< 3%).

Red cell enzyme and serum protein polymorphisms in the western Cape region of South Africa.

Nine red cell enzyme systems: Acid phosphatase-1 (ACP1), adenosine deaminase (ADA), adenylate kinase-1 (AK1), esterase D (ESD), 6-phosphogluconate dehydrogenase (PGD), phosphoglucomutase first and second loci (PGM1, PGM2), carbonic anhydrase-2 (CA2) and glyoxalase-I (GLO1); and three serum protein systems: haptoglobin (HP), transferrin (TF) and properdin factor B (BF), were examined in four populations--Caucasoids, "Cape Coloureds", Cape Malays and Negroes--in the western Cape region of South Africa. The results show distinct differences between the four groups for several genetic markers.

HLA-Dw 'RSH': a new HLA-Dw specificity associated with HLA-DRw18(3).

The present study describes a new HLA-Dw specificity, Dw'RSH'. HLA-Dw'RSH' is associated with DRw18(3) and is clearly different to the DRw17(3) associated specificity Dw3. Dw'RSH' was shown to be the most common Dw specificity found in the South African (SA) Negroes (gf = 0.10) and was less common in Cape Coloureds (gf = 0.01). The specificity was absent in the SA Caucasoids tested. Dw'RSH' is part of the common Negro haplotype Bw42, DRw18, DQw4 which is seen as commonly in the SA Negroes as the B8, DRw17, DQw2, Dw3 haplotype is seen in the Caucasoids.

New HLA-DR2-related specificities detected in South African blacks and individuals of mixed ancestry.

This study describes a new HLA-DR2-related specificity DR2LUM (CT) present in South African Blacks and individuals of mixed ancestry (Cape Coloureds). It can be distinguished from the "classic" DR2 specificities. DRw15 and DRw16, using serological and Southern blot techniques. Although no HLA-Dw specificity could be assigned to the DR2LUM(CT) cells, borderline typing reactions with Dw2 HTCs were observed. Southern blot analysis using a DRB probe and the TaqI enzyme has shown that DR2LUM(CT) shared a 1.6 kb fragment with DRw15 and a 4.7 kb fragment with DR1 and DRw10, indicating sequence homology between DR2LUM(CT) and these alleles. In addition, another unusual HLA-DR2 haplotype was found. The DR antigen was typed serologically as DRw16 but showed a combination of restriction fragments which are associated with both the DRw15 and DRw16 specificities. This study demonstrates the value of investigating non-Caucasoid populations in further characterizing the polymorphisms of the HLA class II genes.

HLA frequencies in the Indian population of Johannesburg.

The HLA class I antigen and haplotype frequencies of the three major Indian groups resident in the Johannesburg area, i.e. Hindus, Muslims and Tamils, were determined. The HLA-A, B and C antigens were tested in 460 healthy individuals. There were striking differences in antigen and haplotype frequencies between the various groups. Of interest was the finding of a complete lack of Aw34 in any of these groups. Although different haplotype frequencies appeared prominent in the different groups, all three groups demonstrated the haplotypes Aw33, B44, B35, Cw4 and B7, Cw7 in linkage disequilibrium. The results indicate dissimilarities between the various groups, underscoring the fact that use of these analyses is essential for the various applications of HLA testing.

Facilities for treatment and patients on renal replacement therapy in South Africa. A report on the 1982 registration.

The 1982 annual registration has revealed that on 31 December 1981, a total of 1 198 sufferers of end-stage renal disease were being maintained by 22 South African treatment centres. Of these 729 were treated by dialysis (537 by in-centre haemodialysis, 47 by home haemodialysis, 28 by intermittent peritoneal dialysis and 117 by continuous ambulatory peritoneal dialysis). Eight of the centres with transplantation programmes were maintaining an additional 469 patients with functioning grafts. The overall treatment rate was 46,9 per million population.

DBP (vitamin D binding protein) and BF (properdin factor B) allele distribution in Namibian San and Khoi and in other South African populations.

The genetic polymorphism of vitamin D binding protein (DBP) and of properdin Factor B (BF) was determined in unrelated Namibian San and Khoi, and in South African Blacks, Caucasoids and Cape Coloureds. Alleles have been confirmed by segregation patterns in family studies. The DBP phenotypes were identified by isoelectric focusing on ultrathin polyacrylamide gels and the BF phenotypes were identified by electrophoresis on 1% agarose gels; both methods were followed by immunofixation. The DBP and BF allele frequencies for all population groups were found to be in accordance with Hardy-Weinberg equilibrium. DBP*1S and BF*S allele frequencies in the San, Khoi and Blacks were similar; their frequency was far lower than in Caucasoids. The frequencies of the DBP*1F and BF*F were also similar in the San, Khoi and Blacks; however, the allele frequency was much higher in these groups than in Caucasoids. These differences were statistically significant (P < 0.001).

HLA-A,B,C, and DR antigens, GLO I and Bf marker profiles in 75 Cape coloured patients with systemic lupus erythematosus (SLE).

HLA-A,B,C and DR antigens were tested in 75 Cape Coloured systemic lupus erythematosus (SLE) patients, and the GLO I and Bf markers in 51. The patients with HLA-DR2 had a relative risk significantly greater than one (p=0.0005). Twenty-two (29%) patients had only one detectable DR antigen. Of these, 11 (50%) were found to have DR2 only. The HLA-DR7 antigen was associated with severe disease (p less than 0.02). Bf and GLO I markers were not associated with SLE.

HLA-A, B, C, DR and DQ polymorphisms in three South African population groups: South African Negroes, Cape Coloureds and South African Caucasoids.

The HLA class I and II phenotypes of the three population groups in the Cape Province of South Africa were determined. The HLA-A,B, and C antigens were tested in 1027 South African Negroes (Xhosa), 3716 Cape Coloureds and 1059 South African Caucasoids. This is the first study which has also included the class II antigens in the Southern African Negroes (Xhosa). The numbers tested for the DR and DQ antigens were smaller, as only typings done after the 8th Histocompatibility Workshop were included. A comparison was made between the frequencies in the Xhosa, the Cape Coloureds and the South African Caucasoids as well as the Nigerians, another group who also belong to the Bantu-speaking division of African Negroes and who were recently studied. The antigen, gene and haplotype frequencies were estimated in all three groups, and the genetic distances calculated. Striking differences in gene and haplotype frequencies between the various populations were seen. For example, Bw42 had a phenotype frequency of 0.062 in the Cape Coloureds, 0.213 in the Xhosa and 0.004 in the South African Caucasoids. The Xhosa showed marked differences in HLA distribution compared to the other Negro group (Nigerians), which can be attributed to a Khoisan admixture, e.g. HLA-DR4 had a phenotype frequency of 0.134 in the Xhosa and only 0.010 in the Nigerians. The haplotype B8,DR3, seen in association with many autoimmune diseases, had a significant delta value in all three populations.