Further evidence of an Amerindian contribution to the Polynesian gene pool on Easter Island

Available evidence suggests a Polynesian origin of the Easter Island population. We recently found that some native Easter Islanders also carried some common American Indian (Amerindian) human leukocyte antigen (HLA) alleles, which probably were introduced before Europeans discovered the island in 1722. In this study, we report molecular genetic investigations of 21 other selected native Easter Islanders. Analysis of mitochondrial DNA and Y chromosome markers showed no traces of an Amerindian contribution. However, high-resolution genomic HLA typing showed that two individuals carried some other common Amerindian HLA alleles, different from those found in our previous investigations. The new data support our previous evidence of an Amerindian contribution to the gene pool on Easter Island.     

HLA study in Bolivian Quechua Amerindians from Titikaka Lake Area

Quechua Amerindians established Inca Empire and chose Cuzco as their capital. Their language is closely related to that of Aymara ethnic group and both of them were originated from Titikaka Lake Altiplano area. In the present study we have analyzed Bolivian Quechua HLA profile and found that it has common characters with other Andean and Pacific Amerindians (Uros, Aymaras, Lamas, Mapuches, Athabascan), and Pacific Islanders, including Easter Islanders: relatively high frequency of HLA-A*24 (:02), class II haplotypes DRB1*08:02-DQB1*04:02, and DRB1*04:03-DQB1* 03:02. Titikaka Lake area prehistoric populations: Quechua, Aymaras and Uros are closely related according to HLA Nei DA genetic distances and other HLA traits: they built up Tiwanaku culture, which resembles that of Easter Island (i.e.: similar giant heads); later, Quechuas also moved to Cuzco. This genetic reletedness together with Easter Island and Titikaka Lake Tiwanaku (Bolivia, Peru) cultural common similarities support a prehistoric Pacific people/Amerindians gene flow.     

HLA in Colombia Wayu from Guajira Peninsula Amerindians: Pacific Ocean relationships

Wayu Amerindians live around Guajira Peninsula shared by Colombia and Venezuela. Wayu from Colombia have been studied for their HLA profile and these data put in context with both genetic and cultural relatedness to Pacific Islanders.HLA-A*24 and HLA-B*35 (most likely HLA-A*24:02 and HLA-B*35:05) and HLA-DRB1*04:03 and HLA-DQB1*03:02 are shared both by Wayu and other Amerindians and Pacific Islanders in specific high frequency. Our findings further suggest a genetic relationship between Amerindians (also Wiwa/Arsario and Chimila from Colombia; Uros from Peru) and Pacific Islanders. Titikaka Lake (Peru/Bolivia) Amerindians (Aymara, Uros and Quechua) share also cultural traits, like Tiwanaku (Titikaka Culture giant statues) and Easter Island Culture giant statues or “Moais”.     

Molecular genetic studies of natives on Easter Island: evidence of an early European and Amerindian contribution to the Polynesian gene pool

Most archaeological and linguistic evidence suggest a Polynesian origin of the population of Easter Island (Rapanui), and this view has been supported by the identification of Polynesian mitochondrial DNA (mtDNA) polymorphisms in prehistoric skeletal remains. However, some evidence of an early South American contact also exists (the sweet potato, bottle gourd etc.), but genetic studies have so far failed to show an early Amerindian contribution to the gene pool on Easter Island. To address this issue, we analyzed mtDNA and Y chromosome markers and performed high-resolution human leukocyte antigen (HLA) genotyping of DNA harvested from previously collected sera of 48 reputedly nonadmixed native Easter Islanders. All individuals carried mtDNA types and HLA alleles previously found in Polynesia, and most men carried Y chromosome markers of Polynesian origin, providing further evidence of a Polynesian origin of the population of Easter Island. A few individuals carried HLA alleles and/or Y chromosome markers of European origin. More interestingly, some individuals carried the HLA alleles A*0212 and B*3905, which are of typical Amerindian origin. The genealogy of some of the individuals carrying these non-Polynesian HLA alleles and their haplotypic backgrounds suggest an introduction into Easter Island in the early 1800s, or earlier. Thus, there may have been an early European and Amerindian contribution to the Polynesian gene pool of Easter Island.     

HLA-DR,DQ sequence polymorphisms in Polynesians, Micronesians, and Javanese.

The origins of the Polynesians remain an enigma. Linguistic reconstructions of proto-Austronesian languages suggest a shared origin for Polynesians, Micronesians, and Javanese with dispersal from northern Borneo and Sulawesi. Analysis of 810 chromosomes for nucleotide sequence polymorphism at HLA-DRB1, DRB3, DRB5, DQA1, and DQB1 loci in Polynesian (Rarotonga, Western Samoa, and Niue), Micronesian (Nauru and Kiribati), and Javanese populations showed virtually no overlap of HLA class II haplotypes between contemporary Polynesians and Javanese. Further, there were marked differences in population distributions of some HLA-DRB1 alleles that could not be distinguished in earlier serologic or restriction fragment length polymorphism (RFLP) studies, e.g., for DR12, DRB1*1201 had a frequency of 15%-30% in Polynesians (1% in Micronesians and Javanese), whereas DRB1*1202 had a frequency of 28%-38% in Micronesians and 51% in Javanese (1% in Polynesians). A novel DR6-related allele, DRB1*1408, was found in all three Polynesian study populations. The Polynesian HLA class II genetic repertoire is not readily derived from the island Southeast Asian gene pool.     

HLA-DR and -DQ DNA polymorphisms: new linkage relationships established by RFLP genomic typing in Polynesians and Melanesians

Class II restriction fragment length polymorphisms (RFLPs) of DR beta, DQ beta, and DQ alpha loci were examined in Polynesians of the southwest Pacific and in non-Austronesian-speaking Melanesians from the Papua New Guinean Highlands. Polynesians, previously considered to have a restricted set of HLA-DR antigens, showed class II gene heterogeneity associated with DR2, DR5, DRw6, and DRw8 RFLPs. Furthermore, Melanesians and Polynesians share certain antigens such as DRw6 and DRw8, but the DR beta 2 genes associated with DRw6 and the DQ genes associated with DRw8 are population-specific and show little or no overlap. This study has shown that genetic analysis of closely linked polymorphic genes is a powerful anthropological tool and supports the view that Polynesians represent an independent colonizing group in the Pacific, rather than a group evolved from within Melanesia.     

Dental variation of ryukyu islanders: A comparative study among Ryukyu,Ainu, and other Asian populations

The presence or absence of 24 nonmetric dental traits was examined to investigate the inter‐ and intraregional variation of Ryukyu Islanders. We compared the dentition of the Kadena sample from the central district of Okinawa Island in the Ryukyu Island chain to those of samples from Nakijin from the northern district of the same Okinawa Island, Tokunoshima, another island of the Ryukyu Island chain, main‐island Japanese in Kagoshima and Tokyo, Hokkaido Ainu, Atayal in Taiwan, and Pashtuns and Tajiks in Afghanistan. Many traits of the Ryukyu Islanders were found to be close to those of the main‐island Japanese; however, several were intermediate between those of the main‐island Japanese and the Ainu or Atayal. The intraregional variation in the Ryukyu Islanders was comparable to that in the main‐island Japanese. This result supports the influence of a complex gene flow to the Ryukyu Islanders, as suggested by some genetic studies. Among the populations compared here, that closest to the Ainu was the population of Tokunoshima. Am. J. Hum. Biol. 15:127–143, 2003. © 2003 Wiley‐Liss, Inc.     

Restriction fragment length polymorphisms associated with the factor VIII and factor IX genes in Polynesians.

New Zealand Maoris (72 X chromosomes) have been compared with Pacific Island Polynesians (121 X chromosomes) and Caucasian New Zealanders (51 X chromosomes) as a control group to determine the allelic frequency of six RFLPs associated with the genes for two X linked diseases (haemophilia A and haemophilia B). RFLPs examined were BclI, XbaI, and BglI within the factor VIII gene, the factor VIII extragenic TaqI system, and the factor IX intragenic TaqI and XmnI sites. The information obtained facilitates the design of strategies for both carrier detection and prenatal diagnosis of haemophilia A within these groups. Strong linkage disequilibrium was observed between the factor VIII BclI and XbaI sites in Polynesians. Genetic counselling for Polynesians with haemophilia B continues, however, to rely on phenotypic diagnosis. The RFLP data from the two separate loci on the X chromosome in Polynesians show similarities with Chinese and Japanese populations, reinforcing theories of an early Polynesian ancestry originating in east Asia.     

HLA in Uros from Peru Titikaka Lake: Tiwanaku,Easter and Pacific Islanders

Uros people live in floating reed islands in Titikaka Lake in front of Puno town (Peru). They could have started Tiwanaku culture and shared genes and culture with Pacific Islanders; it is particularly relevant the giant hat covered men statues found in both Tiwanaku at Titikaka Lake shore and Easter Island (3700 km far from Chile in Pacific Ocean). These giants monoliths are very similar one another and unique in America and Pacific Islands. The following HLA alleles are shared in a specifically high frequency between Uros and Pacific Islanders : HLA-A*24:02, HLA-B*35:05, HLA-B*48:01, HLA-DRB1*04:03, HLA-DRB1*08:02 and HLA-DRB1*09:01. Uros also have 3 unique HLA haplotypes: A*24:02-B*15:04 ? DRB1*14:02-DQB1*03:01, A*68:01:02-B*35:05-DRB1*04:03-DQB1*03:02, A*24:02-B*48:01-DRB1*04:03-DQB1*03:02. Also Uros seem to be one of the most ancient population in Titikaka Lake that could have started Tiwanaku culture. Prehistoric contacts between Amerindians and Pacific Islanders are strongly suggested by genetic and cultural traits. It is not discarded that Uros could have come from Pacific Islands: Uros show melanic skin and are dolichocephalic; in contrast, surrounding Aymara people have a clear skin and are brachicephalic. The Kon-Tiki project led by Thor Heyerdahl showed that a simple sailing is possible between Peru and Polynesia Islands; also, the most ancient skull found in America is of black origin: Luzia, suggesting that first America peopling was also carried out by Black/coloured people.     

Towards understanding the origin and dispersal of Austronesians in the Solomon Sea: HLA class II polymorphism in eight distinct populations of Asia-Oceania.

HLA class II nucleotide sequence polymorphisms were examined in eight ethnic groups of Asia-Oceania using DNA typing methods. Allele frequencies and characteristic DR/DQ haplotypes were determined and compared with those of other populations of Asia-Oceania. Genetic distances were measured to show the genetic relationship within the studied populations as well as between the studied populations and previously published populations. Phylogenetic trees were constructed based on HLA allele frequencies using the neighbour-joining method. The populations, mainly Trobriand Islanders, Roro, Tolai, Western Samoans and Taiwanese Aborigines, are characterized by a reduced diversity at the HLA loci examined, especially for DPB1. The high frequency of the 'Asian'-specific DPB1*0501 allele in Trobrianders and Roro, but also in Western Samoans and Taiwanese Aborigines, was the most striking result. The prevalence of DPB1*0501 and the short genetic distance from Trobriander and Roro to Taiwanese Aborigines provide evidence that the origin of the Austronesian odyssey is south-east Asia, and Taiwan could be an important part of it. The relatedness of Trobrianders to the Polynesian population from Western Samoa indicates a probable recent common ancestor. The observed lack of diversity may reflect bottleneck(s) and/or limited diversity of the founding population. Analysis of HLA class I antigens, together with mt-DNA and Y-chromosomal studies, will give us further information about the settlement of the Trobriand and other islands during the colonization of the Pacific.     

Frequencies and significance of HLA genes in Amerindians from Chile Cañete Mapuche

Mapuche Amerindians live now widespread in Central South Chile and Argentina and speak “Mapudungun”, an unclassified language. A group of Chilean Mapuche was studied for HLA genes using standard techniques. Typical Amerindian HLA genes and haplotypes are found in the population, like HLA-DRB1*14:02, −08:02 and class II haplotype DRB1*08:02-DQB1*04:02. However, these and other genes are also common in Pacific Islanders. Thus, relatedness of First America Inhabitants with some Pacific Islanders is stressed. Evidences of Pacific and Atlantic cultural and genetic exchange, probably in both directions, and California Man settlements found since 130,000 years ago makes it necessary a revision of Americas peopling. This study may be also useful for medical Mapuche use in Transplantation and HLA and disease Epidemiology.     

Towards understanding the origin and dispersal of Austronesians in the Solomon Sea: HLA class II polymorphism in eight distinct populations of Asia-Oceania

HLA class II nucleotide sequence polymorphisms were examined in eight ethnic groups of Asia-Oceania using DNA typing methods. Allele frequencies and characteristic DR/DQ haplotypes were determined and compared with those of other populations of Asia-Oceania. Genetic distances were measured to show the genetic relationship within the studied populations as well as between the studied populations and previously published populations. Phylogenetic trees were constructed based on HLA allele frequencies using the neighbour-joining method. The populations, mainly Trobriand Islanders, Roro, Tolai, Western Samoans and Taiwanese Aborigines, are characterized by a reduced diversity at the HLA loci examined, especially for DPB1. The high frequency of the ‘Asian’-specific DPB1*0501 allele in Trobrianders and Roro, but also in Western Samoans and Taiwanese Aborigines, was the most striking result. The prevalence of DPB1*0501 and the short genetic distance from Trobriander and Roro to Taiwanese Aborigines provide evidence that the origin of the Austronesian odyssey is south-east Asia, and Taiwan could be an important part of it. The relatedness of Trobrianders to the Polynesian population from Western Samoa indicates a probable recent common ancestor. The observed lack of diversity may reflect bottleneck(s) and/or limited diversity of the founding population. Analysis of HLA class I antigens, together with mt-DNA and Y-chromosomal studies, will give us further information about the settlement of the Trobriand and other islands during the colonization of the Pacific.     

Heterogeneity of HLA-A2 in Asia-Oceanic populations

HLA-A2 is one of the most common yet most diversified HLA antigens with 17 subtypes so far identified at the molecular level. A2 subtyping may have significant impact on clinical medicines. We developed a PCR/SSO-based comprehensive typing protocol for HLA-A and investigated the distribution of A2 alleles in regional ethnic groups. A2 was detected with high frequencies in most study populations. A total of 480 A2+ samples were identified and subtyped. The gene frequencies of A2 ranged from 34% in Chinese, 29% in Australian Caucasoids, 21% in Polynesians, 14% in Javanese and 13% in Australian Aborigines. However, in Melanesians and Micronesians A2 was absent. Six A2 alleles were found in the present experiments including A^*0201, 0203, 0205, 0206, 0207 and 0210. In Aborigines all the A2+ donors were typed as 0201. In Caucasoids A^*0201 accounted for 95% of A2+ samples though other three subtypes A^*0203, 0205 and 0207 were also detected. Extraordinary A2 heterogeneity was observed in Asia-Pacific populations where A^*0201 has become a minority. In Chinese all the six A2 alleles were discovered with A^*0201, 0203, 0206 and 0207 as the four major ones. In Javanese A2 was equally divided into A^*0201, 0203 and 0206 while in Polynesians A2 is overwhelmingly dominated by the oriental A^*0206 (71%). Our study also showed that comprehensive DNA matching for A2 would eliminate most A mismatches in the unrelated-donor transplantation in study populations.     

Associated expression of HLA class I and class II antigens on melanoma cells in surgically removed metastases

Malignant transformation of melanocytes and further neoplastic progression may be associated with qualitative and/or quantitative changes in expression of HLA class I and class II antigens. Since previous immunohistochemical studies of surgically removed melanoma lesions have suggested a relationship in the expression of HLA class I and class II antigens, we have investigated the expression of these antigens at the single cell level. Double immunofluorescence staining of frozen sections of melanoma metastases and immunoelectron microscopic double labelling of melanoma cell suspensions prepared from three of these lesions has detected three HLA phenotypes on the large majority of melanoma cells: either both HLA class I and class II antigens, neither HLA antigen or only HLA class I antigens. In four out of the 11 lesions a few melanoma cells were found to express HLA class II antigens and to lack HLA class I antigens. A relationship was also found in the level of expression of HLA class I and class II antigens, as estimated by the intensity of staining with monoclonal antibodies. The level of expression of HLA class II antigens appeared to be similar to or lower than that of HLA class I antigens on the large majority of melanoma cells. This coordinated heterogeneity in the expression of HLA class I and class II antigens by melanoma cells may have implications in the interactions of tumour cells with the host's immune system.     

Pregnancy can induce long-persisting primed CTLs specific for inherited paternal HLA antigens

Previous studies showed that pregnancy can prime the maternal cellular immune response directed against paternal HLA antigens. Primed CTLs specific for inherited paternal HLA antigens (IPA) were found in women who had formed HLA allo antibodies, whereas naive CTLs were present in women who did not form antibodies against the paternal HLA antigens. As HLA allo antibodies may disappear in time, it is not clear which women on the waiting list for transplantation have been sensitized to paternal HLA antigens and are at risk for graft rejection if paternal HLA antigens are shared by the donor organ. The presence of primed CTLs specific for a particular antigen is considered to be a reflection of sensitization.In the present study we investigated whether these primed CTLs persist in women who had been pregnant and had formed antibodies against the inherited paternal HLA class I antigens. For this purpose 14 women who had their last pregnancy 10 years ago were analyzed with respect to IPA-specific CTLp frequencies and the presence of high avidity CTLs directed against inherited paternal HLA class I antigens.Although primed CTLs specific for IPA's were found more frequently in women with persisting alloantibodies, they still can be detected when the antibodies have disappeared. The current data show that primed CTLs directed against inherited paternal HLA antigens towards which antibodies have been formed in the past can persist for more than 10 years after pregnancy. The cellular test used in our study can be useful to detect presensitization in women with a history of pregnancy, who enter the waiting list for transplantation.     

Mitochondrial DNA Variation in Karkar Islanders

We analyzed 375 base pairs (bp) of the first hypervariable region (HVS‐I) of the mitochondrial DNA (mtDNA) control region and intergenic COII/tRNA^Lys 9‐bp deletion from 47 Karkar Islanders (north coast of Papua New Guinea) belonging to the Waskia Papuan language group. To address questions concerning the origin and evolution of this population we compared the Karkar mtDNA haplotypes and haplogroups to those of neighbouring East Asians and Oceanic populations. The results of the phylogeographic analysis show grouping in three different clusters of the Karkar Islander mtDNA lineages: one group of lineages derives from the first Pleistocene settlers of New Guinea‐Island Melanesia, a second set derives from more recent arrivals of Austronesian speaking populations, and the third contains lineages specific to the Karkar Islanders, but still rooted to Austronesian and New Guinea‐Island Melanesia populations. Our results suggest (i) the absence of a strong association between language and mtDNA variation and, (ii) reveal that the mtDNA haplogroups F1a1, M7b1 and E1a, which probably originated in Island Southeast Asia and may be considered signatures of Austronesian population movements, are preserved in the Karkar Islanders but absent in other New Guinea‐Island Melanesian populations. These findings indicate that the Karkar Papuan speakers retained a certain degree of their own genetic uniqueness and a high genetic diversity. We present a hypothesis based on archaeological, linguistic and environmental datasets to argue for a succession of (partial) depopulation and repopulation and expansion events, under conditions of structured interaction, which may explain the variability expressed in the Karkar mtDNA.     

A limited number of HLA epitopes are recognized from HLA class I-specific antibodies detected in the serum of sensitized patients

The goal of this study was to evaluate the epitope specificity of HLA class I-specific antibodies detected in the serum of sensitized patients awaiting retransplantation. The study group consisted of 22 sensitized from previous graft patients, who produced stable IgG HLA class I-specific antibodies. A total of 60 serum samples were screened and analyzed by two techniques in parallel: the antihuman globulin augmented CDC (AHG-CDC) technique and an ELISA technique. All recipients and donors were typed for class I HLA antigens by a standard lymphocytotoxicity technique. The epitope identification was based on class I HLA antigens sequencing, where the multiple immunogenic epitopes are differentially shared among various HLA antigens. The unique epitope configuration on one HLA antigen represents the private epitope of the specific HLA antigen while epitopes shared by more than one HLA antigen represent public determinants. In some HLA antigens (HLA-A1), more than one private epitope has been defined, while in others (HLA-B35, -B51), the private epitopes are not yet known. In a total of 36 antibody reactivity patterns, the majority of the definable IgG HLA class I-specific antibodies corresponded to the A-locus (75%), and only 25% had specificities against the B-locus antigens, although the number of incompatibilities concerning both loci were almost identical (29 for the HLA antigens of the A-locus and 26 for those of B-locus). All patients produced HLA class I-specific antibodies with specificities against the private epitopes of the immunogenic mismatched HLA antigen(s). In 6/21 cases (28.6%), HLA class I alloreactivity spreading to nongraft HLA antigens was detected and 9 public (shared) immunogenic alloepitopes were recognized. In conclusion, appling the epitope analysis of HLA class I-specific antibodies produced by sensitized from previous graft patients, we were able to define the immunogenic alloepitopes. We consider that the immunogenic alloepitopes, during transplantation course, are mainly private epitopes of mismatched HLA antigens and, in certain cases, shared epitopes between the donor alloantigens and other HLA antigens. This knowledge may offer the potential of transplanting sensitized patients through improved donor selection.     

Lymphokines,vol. 5, monoclonal T cells and their products: edited by M. Feldmann and M.H. Schreier. Academic Press,New York, 1982 (xviii + 496 pp., illus.) $55.00

HLA-A and -B antigens were detected on fresh and dried peripheral blood lymphocytes by an enzyme-linked immunosorbent assay. Intact cells fixed to plates with glutaraldehyde were used as antigen and anti-HLA alloantisera as a source of antibodies. Determination of HLA antigens by the ELISA technique was comparable with the complement-dependent cytotoxicity test. The relative stability of HLA antigens as shown in this report and the extensive polymorphism of the HLA system make the ELISA technique a promising tool for the analysis of HLA antigens on non-living cells including, for example, medicolegal investigation of blood stains.     

HLA epitopes – Empirically defined as conformational amino acids sequences of the HLA antigen and are likely to be part of the binding sites of anti-HLA antibodies

Antibodies against HLA antigens are ubiquitous in the sera of transplant patients. Analysis of anti-HLA antibodies specificity has gone through a long history of development using assays like agglutination and lymphocytotoxicity, which utilize lymphocytes, and flow cytometry, which utilize multiplex beads coupled with single antigens. Hundreds of HLA antigens are identified to date, and the realization that antibody reactivity against the antigens is multispecific presented difficulties in accurately defining antibody specificity. Although Cross Reacting Groups (CREG), describing cross reactivity among HLA antigens, were helpful with determining specificity, they proved to be inadequate for the highly sensitized patients. Amino acid sequencing and three-dimensional modeling of the HLA molecules significantly advanced our understating of the HLA antigens and their epitopes. Although sensitive assays for antibody testing advanced analysis, they unmasked additional specificities undetectable by traditional methods, and the presence of naturally occurring anti-HLA antibodies in sera further complicated analysis and underscored the need to understand antibody reactivity and their epitopes. Hundreds of HLA class-I and class-II epitopes were defined by the Tekasaki and Duquesnoy groups and their usefulness in organ transplants were further advanced by a great number of transplant centers. Alloantibody specificities, CREGs, and nondonor specific antigens (NDSA) are now explained by public epitopes     

HLA and MICA polymorphism in Polynesians and New Zealand Maori: Implications for ancestry and health

Data from HLA typing studies have made significant contributions to genetic theories about the Austronesian diaspora and the health of descendant populations. To help further unravel pattern and process elements, we have typed HLA and MICA loci at high resolution in DNA samples from well defined groups of Maori and Polynesian individuals. Our results show a restricted set of HLA class I alleles compared with other well characterised populations. In contrast, the class II HLA-DRB1 locus seems to be diverse in Maori and Polynesians and both groups show high frequencies of HLA-DRB1^∗04:03, -DRB1^∗08:03, -DRB1^∗09:01 and -DRB1^∗12:01. Our survey also provides the first ever MICA datasets for Polynesians and reveal unusual distributions and associations with the HLA-B locus. Overall, our data provide further support for a hybrid origin for Maori and Polynesians. One novel feature of our study is the finding that the gene sequence of the HLA-B^∗40:10 allele in Polynesians is a recombinant of HLA-B^∗55:02 and -B^∗40:01. HLA-B^∗40:10 is in close association with HLA-C^∗04:03, an allele identified as a hybrid of HLA-C^∗04 and -C^∗02. In this respect, our data resemble those reports on Amerindian tribes where inter-allele recombination has been a common means of generating diversity. However, we emphasize that Amerindian gene content per se is only a very minor element of the overall Polynesian genepool. The wider significance of HLA and MICA allele frequencies across the Pacific for modern day health is also discussed in terms of the frequency relative to reference populations of disease known to be associated with specific HLA and MICA markers. Thus, Polynesians and Maori are largely unaffected by “European autoimmune diseases” such as ankylosing spondylitis, uveitis and coeliacs disease, yet there are several Maori- and Polynesian-specific autoimmune diseases where the HLA and MICA associations are still to be determined.