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Genetic variability at the major histocompatibility complex (MHC) is important in any species due to significant role played by MHC for antigen presentation. DQA locus has not been studied for its genetic variability across sheep population in India. In the present study, MHC of sheep at DQA1 and DQA2 loci were evaluated across 17 Indian sheep breeds. Results revealed high degree of heterozygosity (10.34% to 100% for DQA1 and 37.39 to 100% for DQA2). 18 DQA1 alleles and 22 DQA2 alleles were isolated in different breeds. Nucleotide content for DQA region revealed richness of AT content (54.85% for DQA1 and 53.89% for DQA2). DQA1 and DQA2 sequences clustered independently. We could see evidence of divergence of DQA as DQA1 and DQA2 across sheep breeds. Wu-Kabat variability index revealed vast genetic variation across DQA1 and DQA2, specifically at peptide binding sites (PBS) that consisted 21 residues for DQA1 and 17 residues for DQA2. Evolutionary analysis revealed the presence of positive and balancing selection for DQA1 locus, however DQA2 was under purifying selection across sheep breeds. Higher heterozygosity and large diversity at both loci especially at PBS indicated the fitness of the sheep population for evading pathogens and adapt to the harsh tropical climate. [ABSTRACT FROM AUTHOR]

In sheep, MHC variability is studied widely to explore disease association. The aim of the current study was to explore the genetic diversity of Ovar-DRB diversity across sheep breeds of India. Here, Ovar-DRB1 locus was studied across 20 sheep breeds. DRB1 was amplified (301 bp) and sequenced using a PCR-sequence-based typing approach. Results revealed a high degree of heterozygosity across breeds (mean: 73.99%). Overall mean distance for DRB1 was highest in Sangamneri (0.18) and lowest in Madgyal sheep (0.10). There was a higher rate of transition, across breeds. Further, 39 alleles were isolated in different breeds, out of which 10 were new. To allow easy access and use of the immune-polymorphic database, an online database management system was launched (). Nucleotide content across breeds for the DRB1 region revealed the richness of GC content (59.26%). Wu-Kabat index revealed vast genetic variation across peptide binding sites (PBS) of DRB1. Residues 6, 66, 69, 52, and 81, were polymorphic showing utility for antigen presentation. All breeds were under positive selection for DRB1 locus (dN > dS). Study revealed the importance of DRB locus diversity for beta chain specifically at PBS across sheep breeds of the Indian subcontinent and presented evidence of positive selection for DRB owing to its evolutionary significance. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyze the cross-presentation of allopeptides derived from donor major histocompatibility (MHC) molecules by recipient class I MHC molecules in the context of transplantation rejection. Materials and Methods: The MHC molecules were selected based on frequency distribution in the Kerala (India) population using the "allelefrequency. net" database. The most frequent alleles were chosen as donor and recipient alleles. Different immunoinformatics servers such as Netcytotoxic T lymphocyte, NetMHCpan, and Immune Epitope Database MHC I were used for predicting potential T-cell epitopes, and MHC class I epitopes, respectively, from the chosen donor MHC molecule. Three peptides with strong binding affinities in all three predictions were selected for further analysis. The binding of these peptides to the second MHC class I molecule, the recipient one, and transporter associated with antigen processing protein was confirmed by molecular docking using the "AutoDockVina" tool. The binding interactions were visualized using the "Discovery Studio Visualizer" platform. Results: The ability of the selected class I MHC molecule, human leukocyte antigens (HLAs)-A* 11:01, considered the donor allele, to act as an exogenous antigen and to get processed into peptides and presented on the second class I MHC molecule, HLA-A*02:01, considered the recipient allele was confirmed. This immunoinformatics approach could help us to identify potential epitopes from an HLA class I molecule and to measure its ability to get cross-presented on a second HLA class I molecule to trigger the process of cell-mediated rejection. Conclusion: This immunoinformatics approach could help us to identify potential epitopes from an HLA class I molecule and to measure its ability to get cross-presented on a second HLA class I molecule to trigger the process of cell-mediated rejection. Our study provides an easy in silico method for predicting the chances of cell mediated rejection in organ transplantations involving an unrelated donor. We hope that this computational analysis will pave the way for simplifying the process involved in organ rejection prediction. [ABSTRACT FROM AUTHOR]

In this study, we reveal patterns of genetic variation in snow leopards (Panthera uncia) by combining neutral (mtDNA, microsatellites) and adaptive (MHC II-DRB) genes. We collected 56 faecal samples from three locations in India. We observed moderate levels of microsatellite diversity (N = 30; A = 5.6; HO = 0.559). Nine unique MHC II-DRB sequences were identified in four snow leopard samples, of which 8 were novel. We found low levels of polymorphism in MHC class II-DRB exon, which was higher in captive (VA = 9.4%) compared to wild individuals (VA = 7.8%), likely as a result of a population bottleneck. [ABSTRACT FROM AUTHOR]

Current vaccines used for polio are live attenuated oral polio vaccine and inactivated polio vaccine. Recently, in India, the relapse of virulence was observed in attenuated viruses resulting in catastrophic effects. Therefore, the need for the development of multi-epitope subunit vaccine was realised and an immunoinformatics approach to design a multi-epitope subunit vaccine was conceived. Capsid proteins of all the three types of polio strains were utilised to predict major histocompatibility complex class-1 as well as class-2 epitopes. The subunit vaccine was designed with β-defensin at N-terminal followed by cytotoxic T-lymphocytes epitopes and helper T-lymphocytes epitopes connected by compatible linkers. The vaccine construct was further modelled and docked against TLR4 receptor. The high affinity of the construct towards the receptor was observed in the docking study and also substantiated by a 20 ns simulation of the complex. The vaccine construct was cloned in-silico for expression of the protein effectively in a prokaryotic system (Escherichiacoli strain K12). Immuno-simulation of the construct was found to elicit immunoglobulin production effectively in the human body. This designed multi-epitope subunit vaccine is capable of immune response and further studies will help us understand the feasibility of this multi-epitope subunit vaccine. [ABSTRACT FROM AUTHOR]

The genetic diversity at major histocompatibility complex (MHC) in indigenous chicken breeds of India (Ghagus and Nicobari) in comparison with the White Leghorn (WLH) breed was investigated by genotyping the MHC-linked LEI0258 marker. Altogether 38 alleles and 96 genotypes were observed among three breeds. The observed and effective alleles were highest in Ghagus (23, 8.3) followed by Nicobari (14, 3.2) and WLH (10 and 2.2) breeds. The size of alleles ranged from 193 to 489 bp in Ghagus, 193 to 552 bp in Nicobari and 241 to 565 bp in the WLH breed. The number of private alleles was also highest in Ghagus (18) followed by Nicobari (8) and WLH (5) breeds. The most frequent allele was 261 bp in WLH (66 %), 343 bp in Nicobari (50.4 %) and 309 bp in the Ghagus (28.15 %) breed. Observed and expected heterozygosities were highest in Ghagus (0.83, 0.88) followed by Nicobari (0.58, 0.68) and WLH (0.53, 0.54). The genetic distance (Nei) between Ghagus and Nicobari breeds (2.24) was higher as compared to that of Ghagus and WLH (1.23) and that between Nicobari and WLH breeds (0.89). Association analysis revealed significant influence of MHC alleles on body weight, egg production in Ghagus and WLH breeds and antibody titres to Newcastle disease vaccine in the Nicobari breed. [ABSTRACT FROM AUTHOR]

Northeast region of India is a transition zone for two genetically distinct types of water buffalo (Bubalus bubalis) - riverine (Bubalus bubalis bubalis, N=50) and swamp (Bubalus bubalis carabanesis, N=48), wherein, both types of buffalo populations and their hybrids (riverine×swamp, N=49) coexist. In present study, we studied genetic variability of highly polymorphic major histocompatibility complex (MHC) class II-DRB3 gene in 94 riverine-swamp buffaloes of three different locations - central Assam (ASW; riverine and hybrid types), Silchar region (ASW-SL, swamp and hybrid types), Dibrugarh region (ASW-DB, swamp) of Assam through PCR-RFLP. A total of nine HaeIII restriction patterns HaeIII-A to -I, were observed in overall populations, although only six patterns were present in ASW-DB buffaloes. The HaeIII-A, -C, -F and -H patterns were found to be homozygous, accounting about 48 percent of the total buffalo population. Based on DRB3-HaeIII restriction diversity, the genetic divergence was the highest (0.460) between ASW-SL and ASW-DB buffaloes whereas, the lowest (0.063) between ASW and ASW-DB buffaloes among three populations. In Principle Coordinate Analysis (PCA), these populations were found to be distantly located in different coordinates, indicating their genetic distinctness. Our results support that North-east region of India constitute a transition zone for both riverine and swamp buffalo populations, however, with quite distinctness of these mixed populations derived through different genetic pools. Polymorphic DRB3 locus in these riverine-swamp buffalo populations of North-East region also indicates their genetic richness. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR) expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs) were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency. [ABSTRACT FROM AUTHOR]

The largest contribution of type 1 diabetes mellitus (T1DM) from a single locus comes from several genes located in the major histocompatibility complex on chromosome 6p21. Because DQB1 is the best single genetic marker for T1DM, it is the gene most often used to identify individuals with a high risk of developing disease. As per the data collected from the All India Institute of Medical Sciences, among the human leukocyte antigen (HLA)-DRB1 genes, HLA-DR3 showed strongest association with the disease; however, unlike Caucasians and other populations, DR4 was not significantly increased in these patients. HLA-DR10, 11, 13, and 15 showed a negative association with the disease as they were reduced in these patients. In India, the relative risk of developing T1DM is higher with the DR3-DQ2 haplotypes as compared to DR4-DQ8 haplotypes. Studies have shown that in North India, the relative risk for T1DM is comparatively higher (>30) with the DQ2/DQ8 genotype, but is relatively lower (approximately 18) for the DQ2/DQ2 genotype. In addition, the three sets of HLA-B-DR3 haplotypes, mainly B58-DR3, B50-DR3, and B8-DR3 have shown to have modulated susceptibility for T1DM in India and worldwide. New interventions that will be tested in the future will be conducted through T1DM TrialNet, a collaborative network of clinical centers and experts in diabetes and immunology. These studies will identify unaffected first-degree relatives with beta cell autoantibodies who will be eligible for new interventions. [ABSTRACT FROM AUTHOR]

The Austroasiatic linguistic family disputes its origin between two geographically distant regions of Asia, India, and Southeast Asia, respectively. As genetic studies based on classical and gender-specific genetic markers provided contradictory results to this debate thus far, we investigated the HLA diversity (HLA-A, -B, and -DRB1 loci) of an Austroasiatic Munda population from Northeast India and its relationships with other populations from India and Southeast Asia. Because molecular methods currently used to test HLA markers often provide ambiguous results due to the high complexity of this polymorphism, we applied two different techniques (reverse PCR-SSO typing on microbeads arrays based on Luminex technology, and PCR-SSP typing) to type the samples. After validating the resulting frequency distributions through the original statistical method described in our companion article (Nunes et al. 2011), we compared the HLA genetic profile of the sampled Munda to those of other Asiatic populations, among which Dravidian and Indo-European-speakers from India and populations from East and Southeast Asia speaking languages belonging to different linguistic families. We showed that the Munda from Northeast India exhibit a peculiar genetic profile with a reduced level of HLA diversity compared to surrounding Indian populations. They also exhibit less diversity than Southeast Asian populations except at locus DRB1. Several analyses using genetic distances indicate that the Munda are much more closely related to populations from the Indian subcontinent than to Southeast Asian populations speaking languages of the same Austroasiatic linguistic family. On the other hand, they do not share a closer relationship with Dravidians compared with Indo-Europeans, thus arguing against the idea that the Munda share a common and ancient Indian origin with Dravidians. Our results do not favor either a scenario where the Munda would be representative of an ancestral Austroasiatic population giving rise to an eastward Austroasiatic expansion to Southeast Asia. Rather, their peculiar genetic profile is better explained by a decrease in genetic diversity through genetic drift from an ancestral population having a genetic profile similar to present-day Austroasiatic populations from Southeast Asia (thus suggesting a possible southeastern origin), followed by intensive gene flow with neighboring Indian populations. This conclusion is in agreement with archaeological and linguistic information. The history of the Austroasiatic family represents a fascinating example where complex interactions among culturally distinct human populations occurred in the past. [ABSTRACT FROM AUTHOR]

Bengal tigers are highly endangered and knowledge on adaptive genetic variation can be essential for efficient conservation and management. Here we present the first assessment of allelic variation in major histocompatibility complex (MHC) class I and MHC class II DRB genes for wild and captive tigers from India. We amplified, cloned, and sequenced alpha-1 and alpha-2 domain of MHC class I and beta-1 domain of MHC class II DRB genes in 16 tiger specimens of different geographic origin. We detected high variability in peptide-binding sites, presumably resulting from positive selection. Tigers exhibit a low number of MHC DRB alleles, similar to other endangered big cats. Our initial assessment-admittedly with limited geographic coverage and sample size-did not reveal significant differences between captive and wild tigers with regard to MHC variability. In addition, we successfully amplified MHC DRB alleles from scat samples. Our characterization of tiger MHC alleles forms a basis for further in-depth analyses of MHC variability in this illustrative threatened mammal. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a multifactorial disease with an early age of onset, in which the insulin producing beta cell of the pancreas are destroyed because of autoimmunity. It is the second most common chronic disease in children and account for 5% to 10% of all diagnosed cases of diabetes. India is having an incidence of 10.6 cases/year/100,000, and recent studies indicate that the prevalence of type 1 diabetes in India is increasing. However in view of poor health care network, there is no monitoring system in the country. Of the 18 genomic intervals implicated for the risk to develop type 1 diabetes, the major histocompatibility complex (MHC) region on chromosome 6p21.31 has been the major contributor estimated to account for 40-50%, followed by 10% frequency of INS-VNTR at 5' flanking region of the insulin gene on chromosome 11p15.5. However, population studies suggest that > 95% of type 1 diabetes have HLA-DR3 or DR4, or both, and in family studies, sibling pairs affected with type 1 diabetes have a non-random distribution of shared HLA haplotypes. As predisposing genetic factors such as HLA alleles are known, immunological interventions to prevent type 1 diabetes are of great interest. In the present study we have reviewed the status of molecular genetics of the disease and the approaches that need to be adopted in terms of developing patient and suitable control cohorts in the country. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rejection of semiallogenic foetus in recurrent spontaneous abortion (RSA) has been postulated to be a consequence of genetic and immunological phenomena. AIM: To evaluate the role of human leukocyte antigen (HLA) alleles in RSA in Indian couples. SETTINGS AND DESIGN: A case-control study. MATERIALS AND METHODS: Eighty-one randomly selected couples with unexplained three or more RSAs and a control group of 97 couples with live birth belonging to the same ethnic background, referred to the Gynaecology Department, KEM Hospital were included in the case-control study. Serological HLA A and B typing was done followed by molecular subtypes, defined using PCR-SSOP technique for HLA A, B, and C in 40 couples and DRB1* and DQB1* in 28 couples which were then compared with appropriate case 46 and 88 controls. RESULTS: Serologically A3 (15.43% vs. 4.43%; odds ratio (OR) = 4.34; P = 0.0002) and B17 (25.3% vs. 11.34%; OR = 3.49; P = 0.0001) were increased. Haplotype A1-B17 was significantly increased. Molecular subtyping revealed that A*030102 (11.25% vs. 4.34%; OR = 3.00; P = 0.07), B*5701 (11.25% vs. 1.08%; OR = 13.10; P = 0.003), Cw*120201 (25% vs. 4.34%; OR = 10.50; P = 2.05E-05), HLA DRB1*030101 (17.85% vs. 3.40%; OR = 7.6; P = 0.0001), DRB1*150101 (32.14% vs. 13.63%; OR = 4.8; P = 0.0003), and DQB1*060101 (35.71% vs. 29.34%; OR = 2.3; P = 0.004) were significantly increased in patients. A differential association was noticed when compared with reported world RSA patients. CONCLUSION: The HLA alleles A*030101, B*5701, Cw*120201, DRB1*030101, and DRB1*150101 as well as their associated ancestral haplotype may play a significant role in development of RSA in India. [ABSTRACT FROM AUTHOR]

We have used molecular methods to determine the frequencies of human leukocyte antigen (HLA)-A, -B and -C alleles in normal, healthy, unrelated individuals from North India using polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes as there is no comprehensive report showing molecular diversity of all the class-I alleles present in North Indians. A*0101, A*0206, A*0301, A*1101, A*6801, A*2401 and A*3101 were the most prevalent alleles of the A locus with 91.11% of the samples showing heterozygosity. At the HLA-B locus a total of 47 B locus alleles were observed and the only allele found with an allele frequency of 15% was B*5801. Other frequent B-locus alleles observed were B*5101, B*3503 and B*4006 with relatively less frequent alleles like B*5201, B*3501, B*0702, B*4403, B*5701, B*1801 and B*5501. Of the samples studied 92.31% were heterozygous for B-locus alleles. Cw*0602 and Cw*0401 were the most frequent C-locus alleles. Other frequent C-locus alleles were Cw*0102, Cw*0302, Cw*0701, Cw*0702, Cw*1202, Cw*1203, Cw*1502 and Cw*1503. HLA alleles common in Africans like B*5801, A*68012, B*5301, B*44032, B*4006 and Cw*1701 were observed in the North Indians besides oriental alleles like B*1301, B*1502 and B*4001 confirming that the genetic make-up of North Indians is Caucasoid with elements of Mongoloid and Negrito races. Some new/rare alleles like B*1802, described as a new allele from Thailand and B*8101, described earlier in a Bubi population were also observed although with low frequencies, showing the diversity of HLA class-I alleles present in the North Indians. [ABSTRACT FROM AUTHOR]

Asiatic lions ( Panthera leo persica), whose only natural habitat in the world is the Gir forest sanctuary of Gujarat State in India, are highly endangered and are considered to be highly inbred with narrow genetic diversity. An objective assessment of genetic diversity in their immune loci will help in assessing their survivability and may provide vital clues in designing strategies for their scientific management and conservation. We analyzed the comparative sequence polymorphism at exon 2 and exon 3 of major histocompatibility complex (MHC) class I in three groups of lions, i.e. wild Asiatic (from Gir forest), captive-bred Asiatic (from zoological parks in India), and Afro-Asiatic hybrid groups (from zoological parks in India) through polymorphism chain reaction-assisted sequence-based typing. The two exons were amplified, cloned, sequenced, and analyzed for polymorphism at nucleotide and putative translated product level. The analysis revealed extensive sequence polymorphism not only between clones derived from different lions but also the clones derived from a single lion. Furthermore, the wild Asiatic lions of Gir forest exhibited abundant sequence polymorphism at MHC class I comparable with that of Afro-Asiatic hybrid lions and significantly higher than that of captive-bred Asiatic lions. We hypothesize that Asiatic lions of Gir forest are not highly inbred as thought earlier and they possess abundant sequence polymorphism at MHC class I loci. During this study, 52 new sequences of the multigene MHC class I family were also identified among Asiatic lions. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether a common diabetic haplotype, including human leukocyte antigen (HLA)-B8 and HLA-DR3, in Northern India is the same haplotype as the European HLA-B8-DR3 haplotype. DNA samples from Northern Indian subjects selected on the basis of HLA-B8 and HLA-DR3 were tested for microsatellite and single nucleotide polymorphism alleles throughout the major histocompatibility complex (MHC). It was found that the Indian samples represent a conserved haplotype in which all alleles were shared by Indian subjects with HLA-B8 and HLA-DR3, but were different to those that are characteristic of the European 8.1 ancestral haplotype. The Indian and European haplotypes share HLA-B*0801, HLA-DRB1*0301 and HLA-DQB1*02 but differ for subtypes of HLA-Cw*07 and HLA-DRB3 and all central MHC alleles tested. In contrast, Indian subjects selected on the basis of HLA-B58 ( 1–17 ) and HLA-DR3 shared the same alleles at other MHC loci as have been described in the common Chinese haplotype with HLA-B58/17 and HLA-DR3. A third haplotype, HLA-B50/21 and HLA-DR3, was also found to be highly conserved but shares little in common with the other two HLA-DR3-containing Indian haplotypes. [ABSTRACT FROM AUTHOR]

Assesses the association of the major histocompatibility complex (MHC) genes with susceptibility to leprosy in a case-control study of Bengali leprosy patients from Calcutta, India. Influence of host MHC on both susceptibility to leprosy per se and to leprosy types; Association of vitamin D receptor (VDR) genotype with leprosy type; Effect of VDR polymorphism on the type and strength of the host immune response.

Genetic variation and differentiation of five ethnic groups from Punjab, North-West India was characterized by analyzing data on polymorphic Alu insertions (POALINs) within the class I genomic region of major histocompatibility complex (MHC), which is completely non-existent in Indian population. The haplotype frequency, distribution and heterozygosity among these groups and their potential implications in molecular anthropology and evolutionary studies were also determined. A total of 479 unrelated healthy individuals representing five different ethnic groups: Banias, Brahmins, Khatri, Jat Sikhs and Scheduled Castes were genotyped for five MHC Alu elements (AluHG, AluMICB, AluHJ, AluTF and AluHF) using polymerase chain reaction (PCR). All the loci were found to be polymorphic among the studied populations. No significant deviation from Hardy-Weinberg equilibrium was observed, except for the AluHJ locus in Brahmins. The POALINs varied in allele frequency between 0.0260 and 0.4427. The average heterozygosity among the studied groups ranged from 0.1937 in Banias to 0.2666 in Jat Sikhs. The genetic differentiation among the studied groups was observed to be of the order of 0.01302. Single POALIN haplotypes were found to be more frequent than multiple POALIN haplotypes. The results of inter-population differentiations, haplotype frequencies, genetic distances, multidimensional scaling, phylogenetic and structure analyses indicated close genetic relationships between the five ethnic groups of Punjab, North-West India. Analyses of polymorphic Alu loci of MHC genomic region may represent reliable information about the ancestry, demographic history and geographic origins of the various human populations, facilitating better understanding of the evolutionary, forensic and epidemiological prospective., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim To find the incidence of MHC class I chain-related chain A (MICA) alloantibodies in patients undergoing live related donor (LRD) renal transplantation and their association with short-term graft survival. Methods Pre-transplant, consecutive, serum samples of ESRD patients undergoing first renal allograft transplantation were tested for anti-MICA antibodies. Association of various demographics, HLA-A + B + DRB1 mismatches and HLA antibody screen with MICA antibodies was assessed using Pearson’s Chi-square test. A multivariate analysis was also performed to check for potential confounders. The effect of pre-transplant blood transfusions on antibodies against HLA Class 1 & class II, or MICA was studied. Results Out of 646 serum samples for MICA antibodies, 94 (14.6%) were positive and 552(85.4%) negative for MICA antibodies. Patients with MICA antibody had a graft survival 89.3% as compared to 94.7% in patients without MICA antibody (P = 0.01). The hazards ratio for all patients was 3.744 (P = 0.01). MANOVA effect was determined for three factors (HLA antibody, MICA antibody & HLA mismatch) and Graft survival which was statistically significant. Two of the three ANOVA’s were statistically significant viz. MICA antibody and presence of HLA antibody. Conclusions MICA antibodies were present in 14.6% of the patients. Preformed MICA antibodies independently increase the risk of kidney rejection and therefore a guideline should be made for mandatory testing of these antibodies prior to transplant. [ABSTRACT FROM AUTHOR]

Fifty-eight patients with systemic lupus erythematosus (SLE) from Northern India were tissue typed for HLA class I and II antigens. The results revealed an appreciable increase of HLA-DR4 (37.5%) among patients compared with controls (17.9%), P < 0.03. Additionally, haplotype B8-DR3 was encountered frequently in the patient group. The findings suggest an important role of MHC genes in influencing susceptibility to SLE.

Trans-racial analysis of disease associations has improved mapping of MHC-linked susceptibility to Type 1 (insulin-dependent) diabetes mellitus. In this study the contributions of the MHC class II DQA1 and DQB1 genes were investigated. Sequence-specific oligonucleotide gene probing in Type 1 diabetic and control subjects of North Indian origin supported the DQw1.18 allele of the DQB1 gene as a determinant of inherited protection against Type 1 diabetes (RR = 0.12, pc less than 0.05). The A3 allele of the DQA1 gene was positively associated with the disease, (RR = 3.6, pc less than 0.05), as was the DQw2 allele of the DQB1 gene (RR = 4.6, pc less than 0.01). Trans-racial comparison of these disease associations indicates that DQ alleles may directly determine an element of inherited susceptibility to Type 1 diabetes.