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Biomedical subjects

U Shankarkumar

Publications and source records attributed to U Shankarkumar.

At least 19 recordsLinked to original sources
PubMed2005

Cytolytic T lymphocytes (CTLs) from HIV-1 subtype C-infected Indian patients recognize CTL epitopes from a conserved immunodominant region of HIV-1 Gag and Nef.

Analysis of the human immunodeficiency virus type 1 (HIV-1) cytolytic T lymphocyte (CTL) epitopes recognized by the targeted population is critical for HIV-1 vaccine design. Peripheral blood mononuclear cells from 47 Indian subjects at different stages of HIV-1 infection were tested for HIV-1 Gag-, Nef-, and Env-specific T cell responses by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay, using pools of overlapping peptides. The Gag and Nef antigens were targeted by 83% and 36% of responders. Five immunodominant regions, 4 in Gag and 1 in Nef, were identified in the study; these regions are conserved across clades, including the African subtype C clade. Three antigenic regions were also found to be recognized by CTLs of the study participants. These regions were not identified as immunodominant regions in studies performed in Africa, which highlights the importance of differential clustering of responses within HIV-1 subtype C. Twenty-six putative epitopes--15 Gag (10 in p24 and 5 in p17), 10 Nef, and 1 Env (gp 41)--were predicted using a combination of peptide matrix ELISPOT assay and CTL epitope-prediction software. Ninety percent of the predicted epitopes were clustered in the conserved immunodominant regions of the Gag and Nef antigens. Of 26 predicted epitopes, 8 were promiscuous, 3 of which were highly conserved across clades. Three Gag and 4 Nef epitopes were novel. The identification of conserved epitopes will be important in the planning of an HIV-1 vaccine strategy for subtype C-affected regions.

AIDS Vaccines↗
PubMed2005

Immunogenetic association in patients with antineutrophil cytoplasmic antibodies (ANCA) from Mumbai, Maharashtra, India.

Considerable genetic evidence exit for ANCA-associated vasculitis and pathogenesis. HLA A and B alleles identified serologically from 84 ANCA-positive patients were compared with 101 controls. Further subtyping were done in the 27 "pauci-immune" vasculitis patients using the polymerase chain reaction based PCR-SSOP technique and compared with controls (67). The results revealed that HLA A1 (OR=4.00; p value 2.72E-05), B17 (OR=3.38; p value 0.0008) and HLA B40 (OR=2.74; p value 0.001) were significantly increased among ANCA-positive patients when compared with the controls. Further, the molecular subtypes A*0101 (OR=5.04; p value 0.0005), B*5801 (OR=4.47; p value 0.0002) and haplotype A*0101-B*5801 (OR=4.47; p value 0.0001) were significantly increased among the autoimmune patients. The study revealed that HLA A1, B17 and B40 alleles are associated in production of antineutrophil autoantibodies and A*0101-B*5801 haplotype is significantly associated with autoimmune diseases and they may be invariably involved in disease pathogenesis in India.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Molecular diversity of HLA-Cw alleles in the Maratha community of Mumbai, Maharashtra, western India.

Recent advances suggest a significant role for the HLA-C locus as a target of alloreactions after bone marrow transplantation. The biological importance of products of the HLA-C locus, both as transplant antigens and as ligands for natural killer (NK) cells, is well established. A total of 10 different serologically defined HLA-Cw antigen specificities (Cw1-Cw10) are encoded by the C locus; however, there are now 151 different alleles that can be identified by molecular methods. Serological definition of Cw alleles therefore includes 20-50% blanks, which cannot be detected by the available antisera. We used the molecular method of polymerase chain reaction (PCR)-based sequence-specific amplification and probe hybridization to define Cw alleles in 91 individuals from the Maratha community, and compared the data with data for 92 serologically typed Maratha individuals from India. We identified Cw*12, Cw*14, Cw*15, Cw*16 and Cw*18, along with the serologically identified Cw*01, Cw*02, Cw*03, Cw*04, Cw*06 and Cw*07 alleles. The HLA-Cw blank allele frequency in the Maratha was reduced from 0.5706 to 0.00. Furthermore, by using a molecular technique, it was possible to identify novel allele subtypes, such as Cw*0104, Cw*0203 and Cw*0707, and a high frequency of Cw* 1801 in the Maratha community compared with other Indian and world populations. Our results will have clinical implications in related and unrelated HLA-matched bone marrow transplantation in India.

Alleles↗
PubMed2004

HLA associations in leprosy patients from Mumbai, India.

Genetic predisposition to both disease susceptibility and to host immune response has been postulated. In India, about 64% of leprosy prevalence and 78% of new case detection of the worlds estimated 719,330 cases occur. Convincing results have been reported from studies on HLA class II association in leprosy. However data on HLA class I association are limited and inconsistent. The HLA A, B and C allele distribution in 103 leprosy patients and 101 normal healthy control individuals were studied by microlymphocytotoxicity assay. Further 32 multibacillary leprosy patients along with the 67 controls were studied by molecular high-resolution PCR-SSOP technique. The significant results from the present study were: 1) serologically, a significant increase in HLA A2, A11, B40 and Cw7, while a decrease of A28, B12, B15 and Cw3 were observed among the leprosy patients when compared with the controls; 2) molecular subtyping in multibacillary leprosy patients revealed a significant increase in frequency of HLA A*0203, A*0206, A*1102, B*1801, B*4016, B*5110, Cw*0407 and Cw*0703 while a decrease in the frequency of HLA A*0101, A*0211, B*4006, Cw*03031, Cw*04011 and Cw*0602 leprosy patients was observed when compared with the controls; 3) further haplotypes A*1102-B*4006-Cw*1502; A*0203-B*4016-Cw*0703; A*11-B*40 was significantly increased among the multibacillary leprosy patients when compared with the controls. It seems that HLA class I alleles play vital roles in disease association/pathogenesis.

Alleles↗
PubMed2003

Novel HLA B*2714 and B*2708 allele associations in seronegative spondarthritis patients and haemophilia patients with chronic synovitis in India.

HLA B27 association with seronegative spondarthritis (SSA) has been recognized for over a decade and its association with chronic synovitis in Haemophilia patients has been recently reported. We characterized the HLA B27 subtypes in a cohort of 98 B27 positive individuals with SSA (n = 45), haemophilia with chronic synovitis (n = 21) and normal controls (n = 32), using polymerase chain reaction-based sequence specific primers (PCR-SSP) and reverse line strip (RLS) techniques. The results revealed a significant association for a novel allele B*2714 in SSA along with the previously reported B*2705 allele. We also found a significant association between haemophilia patients with chronic synovitis from India and a hitherto unidentified allele, B*2708.

Arthritis↗
PubMed2003

HLA diversity among Nadars, a primitive Dravidian caste of South India.

South India is one of the oldest geophysical regions mainly occupied by Dravidian language-speaking people. Here a random panel of 61 unrelated Nadar healthy individual from Tamil Nadu State were analyzed and compared with other populations of India and the world. HLA-A, B and C alleles frequencies and their haplotype frequencies were determined by high-resolution typing of genomic DNA. The analysis revealed that the Nadar caste of South India have several characters shared with East Asian populations consistent with the demographic history of South India, as well as specific features including several unique alleles such as A*03011, A*31011, B*15011, B*3501, B*51011, Cw*02022. In addition, haplotypes such as A*31011-Cw*02022-B*3501, A*03011-Cw*04011-B*4406 and A*2402101-Cw*04011-B*51011 are of high frequency in both these populations but are rare or absent in other populations of India and the world. The study suggests that a comparatively lesser degree of genetic admixture occurred between the South Indian and North Indian racial groups than that between South Indian and East Asian groups.

Gene Frequency↗
PubMed2003

HLA A*02 allele and B-associated haplotype diversity in Indians.

Human leucocyte antigen (HLA) A2 is the most heterogeneous allele at the HLA A locus, with approximately 56 different subtypes. Substantial heterogeneity in A*02 distribution has been observed in populations worldwide. HLA A2 allele distribution varies (4-25%) in different Indian populations and castes. HLA B40 is the most common allele associated with A2 haplotypes. In this study, molecular A*02 subtyping in Maratha (western Indian--Aryan) and Nadar (south Indian--Dravidian) caste groups using high-resolution polymerase chain reaction/reverse line strip/sequence-specific oligonucleotide hybridisation (PCR-RLS-SSOP) indicates the presence of 10 subtypes (A*02011, A*0203, A*0205, A*0206, A*0207, A*0208, A*0209, A*0211, A*0222 and A*0236) in variable frequencies. Moreover, A*0211-B*4006 was commonly observed among the north Indian Maratha caste and A*02011-B*4006 among the south Indian Nadar caste groups. HLA A*0211 is found frequently in this population and in Asian Indians, and has been reported with low frequencies in many other populations worldwide. A*0222 has been observed among Hispanics, while A*0236 has been observed exclusively among members of the Maratha caste. The findings demonstrate a substantial heterogeneity among the groups studied that may be a consequence of founder effect, racial admixture or selection pressure due to environmental factors.

Founder Effect↗
PubMed2003

HLA-B27 allele diversity in Indians: impact of ethnic origin and the caste system.

HLA-B27 is a serological specificity which encompasses an increasing number of subtypes that show varied racial/ethnic prevalence in the world. Here, data from 5129 Indians (4500 population and caste; 629 tribal) is compiled from the literature. In addition, HLA-B27 subtyping of 58 positive individuals from Maharastra is presented. Analysis revealed an increased B27 antigen frequency among the north Indian groups (>5%) compared to the south Indian groups (<5%). HLA-B27 subtyping identified B*2704 (34.48%), B*2705 (36.2%), B*2707 (15.51%), B*2708 (10.34%) and B*2714 (3.44%) alleles in the population groups from Maharastra, but these differed in their distribution among the caste and tribal groups studied. The study showed that more extensive subtyping in other Indian caste groups will be necessary to resolve the evolutionary implications of HLA-B27 subtypes and their relationship to disease association in the Indian context.

Alleles↗
PubMed2002

HLA B27 polymorphism in Western India.

We have characterized HLA B27 alleles in a sample population of Maharastra, Western Indians (n = 51), with the aim to investigate the different subtypes present among this population. The study was carried out using polymerase chain reaction with sequence-specific primers (PCR-SSP) and reverse line strip (RLS) techniques. Significant new findings have arisen from this study: B*2704, B*2705, B*2707, B*2708 and B*2714 alleles were found to be present, and two novel B27 alleles, B*2708 and B*2714, were found in this Indian population. In addition, B*2714 was observed in a patient with ankylosing spondylitis. This association has not been previously reported in ethnic groups from India.

Alleles↗
PubMed2002

Common human leucocyte antigen haplotypes in Indians--its implications in finding unrelated compatible bone marrow donors.

All over the world there have been efforts to make unrelated stem cell registries to cater for patients who do not have a compatible family donor and are in need of allogenic stem cell transplantation. Donors of Indian origin are poorly represented all these registries. Approximately 10 million Indians live outside India, and a substantial number of them live in the developed West. Hence when some of these patients of Indian origin need unrelated stem cell donor, they search the available National Marrow Donor Program (NMDP) registry database and invariably do not get a human leucocyte antigen (HLA) matched donor. They come to India, where a haphazard search for the donor ensues and it invariably ends in failure. Hence, we have compiled the data of our laboratory and other published reports in population HLA studies from India and abroad to show several common haplotypes from these studies. It is hoped that this will give the busy clinician an idea whether a search for prospective unrelated stem cell donor for an Indian patient is likely to succeed or not.

Bone Marrow Transplantation↗
PubMed2002

Seronegative spondarthritis and human leucocyte antigen association.

The human leucocyte antigen (HLA) B27 has been associated with seronegative spondarthritis universally, but the associations varies (19-94%) in different Indian population groups. It is possible that this variation is due to patient selection bias. Here, we use strict clinical, radiological and serological criteria to select 79 patients with seronegative spondarthritis (SSA) and compare them with 110 healthy, normal individuals from the same ethnic background. The standard National Institute of Health (NIH) microlymphocytotoxicity assay is used to evaluate HLA B27 status in both groups. Significant association between HLA B27 and AS disease was found (odds ratio [OR]: 72.22; P<0.0001; confidence interval [CI]=1.5-3.8) when compared to the control group. Furthermore, HLA B5 was decreased when compared to the control group (OR: 0.39; P<0.01). Those in the 20-40 age group were more vulnerable, with a male preponderance (7:1) over females. These findings confirm the strong association of the HLA B27 allele with various types of spondarthritis and suggest that allele detection would help in the diagnosis of AS where clinical presentation is unclear and in identifying family members at risk.

Adult↗
PubMed2002

A sensitive micro-platelet ELISA technique for screening anti-HLA antibodies.

An enzyme-linked immunosorbant assay (ELISA) in a Terasaki plate (Micro-Platelet ELISA), using 30000 platelets per well, 2 microL primary antibody (anti HLA antiserum) and 5 microL of secondary antibody (1:2000) are described. Platelets from 30 selected HLA tissue typed cell panel individuals were used to characterize anti HLA A and B antibodies. The first half of the Terasaki tray had platelets in sequence to characterize anti HLA antibodies, while the second half contained anti HLA B antibodies. Results revealed that the HLA specificities of the sera identified by micro-platelet ELISA and microlymphocytotoxicity were concordant. Moreover, split antigens of broader specificities were identified in the Platelet ELISA technique. The advantages of micro-platelet ELISA technique were: (i) it does not require viable/frozen lymphocytes, (ii) reading is very simple and macroscopic, (iii) specificity of the serum is identified with accuracy within the same day, (iv) avoids inter-cell, inter-day variations, (v) complement is not required, (vi) requires only 1/50 volume of the reagents required by conventional ELISA in microtitre plates, and (vii) using platelets isolated from 5 mL of peripheral blood, fifteen thousand sera can be tested. This technique is, thus, very simple, cost effective, and very much suitable for any developing HLA laboratory, which is in the process of developing indigenous HLA reagents.

Autoantibodies↗
PubMed2001

HLA antigen distribution in Jain population from Mumbai, Maharashtra, India.

BACKGROUND & OBJECTIVES: The Indian population is well known for its genetic diversity. Among the numerous endogamous communities, the Jain community from Mumbai is very restricted by custom, marriage and occupation. We present here the HLA antigen distribution of individuals belonging to this endogamous community. METHODS: A total of 161 healthy individuals of the Jain community working or studying in a hospital at Mumbai were selected randomly during 1985-1988. HLA class I and class II antigens were identified by using the standard National Institutes of Health (NIH) microlymphocytotoxicity assay. RESULTS: The phenotypic frequencies of HLA A1, A2, A9, A11, A24, B5, B35, B40, Cw4, DR2, DR3, DR4, DR5 and DR7 were increased while frequencies of HLA A10, A19, A26, A32, B7, B14, B16, B21, B22, B27, B37, Cw2, DR1 and DR9 were decreased when compared with other populations from, Maharashtra. The phenotype frequencies of HLA A26, A28, A30, B18, B40, B56, Cw3, Cw4, DR3, DR4 and DR5 were increased while the frequencies of HLA B7, B15, B16, B22, B37, Cw2, Cw6, DR1 and DR9 were decreased when compared with frequencies in other Indian populations. Two locus haplotype analyses revealed that A9-B5, B35-Cw4, DR2-DQ1 and DR7-DQ2 were significant haplotypes among the positive linkage disequilibrium haplotypes. Whereas A9-B35, B35-Cw1 and DR1-DQ2 were significant haplotypes among the negative linkage disequilibrium haplotypes. INTERPRETATION & CONCLUSION: The study revealed that the Jain population of Mumbai cannot be considered as a single panmictic population with reference to genetic characteristics, this may have a clinical relevance in unrelated donor selection for allogenic bone marrow transplantation in India.

Female↗