Novel and extended HLA class I and II alleles encountered in Kashmiri Brahmin population from North India.

Three novel HLA-A*02:06:01:04, -DRB1*12:02:01:02, -DQB1*03:01:01:07 and five extended HLA-B*51:01:05, -DRB1*12:02:01:01, -DRB1*14:01:01, -DRB1*14:04:01:01, -DRB1*15:04 alleles.

HLA-A*02 repertoires in three defined population groups from North and Central India: Punjabi Khatries, Kashmiri Brahmins and Sahariya Tribe.

The allelic family of HLA-A*02 with a repertoire of approximately 1022 alleles represents the predominant and most heterogeneous group at the HLA-A locus. This remarkable diversity signifies its evolutionary relevance. Its population-specific diversity is attributed to environmental factors and pathogen pressure and can be harnessed in biology and medicine, particularly in disease association and for HLA-based vaccination approaches. We therefore investigated the HLA-A*02 repertoire in two North Indian caste populations, viz Punjabi Khatries (PK, N = 250), Kashmiri Brahmins (KB, N = 160) and a Central Indian tribe Sahariya (ST, N = 100) using Luminex-based high-resolution rSSO method. When required, results were confirmed with high-resolution PCR-SSP and/or next-generation sequencing (NGS). In the three populations evaluated, HLA-A*02 was observed with an overall high phenotypic/allelic frequency, however, A*02 repertoire differed among them. A total of six alleles were observed (A*02:01, *02:03, *02:05, *02:06, *02:07 and *02:11) in the caste groups, compared with four (except *02:05 and *02:07) in the tribals. Our striking observation was the high occurrence of A*02:11 at the repertoire level (80.6% in ST, 39% in PK, 31.8% in KB). Globally, this allele is rare, observed with low frequencies in limited ethnic groups. The primordial A*02:01 allele, representative A*02 allele in most ethnicities was observed as the second predominant allele (PK = 27.3%, KB = 31.8% and ST = 11.9%). Extremely high occurrence of A*02:11 in ST may be representation of ancient Austro-Asiatic genetic pool. In caste populations, the observed A*02 repertoire may be a consequence of natural selection and/or admixture from different populations.

Differential expression of HLA-G and ILT-2 receptor in human tuberculosis: Localized versus disseminated disease.

Human leukocyte antigen-G (HLA-G) is an anti-inflammatory and immunosuppressive molecule that can modulate immune cell activation. The role of HLA-G in tuberculosis, an immune-mediated and chronic bacterial disease remains to be elucidated. We investigated the expression profile of soluble and membrane bound HLA-G in pulmonary TB (PTB), TB pleural effusion (TB-PE, localized disease) and Miliary TB (disseminated form). The expression of HLA-G receptor, ILT-2 was also determined on the immune cells. We observed that the plasma sHLA-G levels were significantly increased in Miliary TB than in TB-PE patients. In contrast, immunophenotyping revealed that the percent frequency of CD3(+) T cells expressing HLA-G was significantly reduced in Miliary TB as compared to TB-PE, whereas frequency of CD14(+) monocytes expressing HLA-G was significantly higher in TB-PE patients. Strikingly in the TB-PE cases, comparison of disease site, i.e. pleural effusion with peripheral blood showed increased expression of both soluble and surface HLA-G, whereas ILT-2 expressing cells were reduced at the local disease site. Furthermore, we demonstrated that in TB-PE cases, HLA-G expression on CD3(+) T cells was influenced by broad spectrum MMP inhibitor. Thus, differential expression of HLA-G could potentially be a useful biomarker to distinguish different states of TB disease.

The Raikas - a unique combination of high prevalence of type 1 diabetes susceptibility genes and near zero incidence of the disease.

The Raikas, a camel rearing tribal group living in the Thar desert of Rajasthan has been reported with a very low incidence of diabetes. We analysed the frequency distribution of HLA alleles in this community and compared the same with the non-Raika group living in the same geographic location and also that of the healthy North Indian (NI) population. The data revealed an exceptionally high phenotype frequency of HLA-DRB1*03 in this community (53%) as compared to the non-Raika group (27.73%, p=7.9E-05) and the NI population (14.6%, p=7.65E06). Further analysis revealed the occurrence of four major DRB1*03 haplotypes in the Raikas: (i) A*26-B*08-DRB1*03 (AH8.2, 11.76%); (ii) A*24-B*08-DRB1*03 (AH8.3, 8.82%); (iii) A*02-B*08-DRB1*03 (3.78%); (iv) A*01-B*08-DRB1*03 (AH8.1v, 0.84%); all of which occurred with a several fold higher frequency in the Raikas than the other two groups. These haplotypes have been reported to be positively associated with T1D in the NI population. The apparent lack of T1D and/or other autoimmune diseases in the Raikas despite the higher occurrence of known disease associated HLA alleles/haplotypes is intriguing and highlights the quintessential role of the environmental factors, food habits and level of physical activity in the manifestation of T1D. Possible influence of other protection conferring genes located on, as yet undefined chromosomal locations cannot be ruled out.