HIV and malaria co-infection in Mumbai, western India.

Background & objectives: Conflicting reports exist regarding the HIV-1 infection on the risk of malaria. A transient almost one-log elevation in HIV viral load occurs during febrile malaria episodes. We prospectively studied malaria patients for HIV infection from Mumbai. Methods: A total of 171 malaria patients and 28,749 normal voluntary blood donors were studied for their HIV status. Diagnosis of malaria was done by microscopical examination of blood. HIV screening was done by detection of HIV-1 & 2 antibodies by micro well ELISA using Enzaids & J Mitra kits followed by confirmation using western blot (Innogenetics, Belgium) analysis. Results: Out of 171 malaria patients 13 (7.6%; Odds ratio= 4.45; p <0.0001) and 521 blood bank donors were found to be HIV reactive. Among 13 HIV reactive patients, eight patients were Elisa borderline reactive and western blot positive (p24), which may be due to cross-reactive antibodies. Five of 13 malaria patients found to be HIV-1 positive by ELISA and by western blot confirming HIV and malaria co-infection. Conclusion: Our findings suggest that HIV-1 and malaria co-infection can’t be ruled out in malaria endemic countries like India.

Human immunodeficiency virus therapeutics and pharmacogenomics.

Pharmacogenomics and pharmacogenetics are promising in development of a personalized treatment approach They are of paramount importance for basic immunology, for peptide based vaccine design (vaccinomics) drug monitoring in clinical setting and molecular pathophysiology of multifactorial diseases like cancer, tuberculosis, cardiac disorders, diabetes, asthma, HIV, etc

Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and nonfamilial vitiligo.

Background: Various studies worldwide suggest that human leukocyte antigen (HLA) region may be involved in the genetic susceptibility of vitiligo but little information is available from India. Aim: To find the HLA associated susceptibility to develop vitiligo in Indian patients and to detect role of HLA in familial vitiligo. Methods: This was a case controlled study which included all patients suffering from vitiligo over a period of one and half years. Clinical details were noted and sera collected from these patients were screened for the presence of HLA class I antibodies. The clinical features and HLA antigens were assessed and comparison was made between patients with familial and nonfamilial vitiligo. Results: Out of 114 patients studied, 84 had family history and 30 had no family history. Patients with family history of vitiligo have higher chances of acquiring vitiligo if first degree relatives are affected compared to if second degree relatives are affected. Family history of vitiligo is associated with an early onset of vitiligo (<20 years). There was no statistically significant difference in the type, stability, and severity of vitiligo in both the groups. HLA results in both the groups revealed increase in HLA A2, A11, A31, A33, B17, B35, B40, and B44 alleles while HLA A9, B13, and B53 alleles were decreased. Family history was associated with HLA A2, A28, A31, and B44 alleles. Early onset of vitiligo (<20 years) was significantly associated with HLA A2, A11, B17, B35, and B44 alleles. The patients with severe affection (>10% area) showed in significant association with HLA A10 and B8. Conclusion: Family history of vitiligo is associated with an early onset of vitiligo. There is no correlation of family history with the type of vitiligo, stability of lesions, and areas involved. Severity is not associated with family history. Apart from other alleles, alleles A2, and B44 play a significant role in vitiligo in the Indian patients.

Association of HLA alleles with hepatitis C infection in Maharashtra, western India.

Background & objectives: Host genetic diversity is believed to contribute to the spectrum of clinical outcomes in hepatitis C virus (HCV) infection. The present study aimed at finding out the frequencies of HLA class I and class II alleles of HCV infected individuals from western India. Methods: Forty three clinically characterized anti-HCV positive patients from Maharashtra were studied for HLA A, B, C, DRB1 and DQB1 alleles by PCR- sequence specific primer (SSP) typing method and compared with 67 and 113 ethnically matched, anti-HCV negative healthy controls from western India. Results: Our analysis revealed an association of HLA alleles HLA A*03 (OR= 16.69, EF, 0.44, P=7.9E-12), A*32 (OR= 1474, EF 0.21, P=1.8E-9), HLA B*15 (OR=14.11, EF 0.39, P=2.18E-10), B*55 (OR= 12.09, EF 0.07, P=0.005), Cw*16 (OR= 7.45, EF 0.12, P=0.001), Cw*18 (OR= 402, EF 0.05, P=0.003), DRB1*03 (OR= 4.01, EF 0.08, P=0.01) and DQB1*03 (OR= 3.02, EF 0.22, P=0.001), with HCV infection. HLA II locus haplotype DRB1*11-DQB1*03 (HF=17.64, OR=5.16, P=0.0001) was significantly increased among HCV infected individuals. Interpretation & conclusions: Our data suggest that among the western Indian population, certain HLA alleles or associated haplotype influence HCV infection as a host genetic factor.

Implications of HLA sequence-based typing in transplantation.

Serology-based conventional microlymphocytotoxicity HLA typing method, which has been regarded as the gold standard in organ and hematopoietic stem cell transplantation, has been replaced now by DNA-based typing. Many laboratories all over the world have already switched over to molecular methods. Microlymphocytotoxicity-based tissue typing was done using commercial sera, while the molecular typing by genomic DNA based. DNA quality and its quantity obtained using various DNA extraction protocols was found to be an important factor in the molecular method of tissue typing in transplant outcome. Many polymerase chain reaction-based molecular techniques have been adopted with far reaching clinical outcome. The sequence-based typing (SBT) has been the ultimate technique, which has been of the highest reliability in defining the HLA alleles. The nonavailability of specific HLA antisera from native populations, large number of blank alleles yet to be defined and comparable low resolution of HLA alleles in SSP or SSOP technique, suggests that highly refined DNA-based methods like SBT should be used as an adjunct to HLA serology and/or low/intermediate/high resolution HLA typing in order to achieve a better transplant outcome.

MHC non -HLA gene polymorphisms in transplantation.

Despite many studies on non-HLA genetic polymorphism its role in transplantation is still not well understood. The NK cell receptor gene, MICA gene and Minor histocompatibility (mHag) system makes the puzzle still more intriguingly complex. Studies on cytokine gene polymorphism have enlightened some interesting associations such as the effect of donor IL-6 genotype on acute rejection in renal transplantation. In the bone marrow transplant where each polymorphism is taken as a risk factor for GVHD necessitates prospective testing of non-HLA gene polymorphism and hence, transplant outcome. Various typing methods are now available to identify the non-HLA genetic polymorphisms. A scenario can be envisaged where polymorphisms associated with transplant outcome are tested prior to transplantation at the same time as HLA typing.

HLA A19 subtypes and B loci related haplotype in selected caste groups from the Indian population.

The Indian population has been broadly classified as Aryans of Northern India and Dravidians of South India. The present study was undertaken to compile available data and investigate the genetic diversity of HLA A19 subtypes in Indians and its associated B locus haplotype frequency distribution at the population level. The study revealed that A33 was common among the selected North Indian caste groups (Aryans) while A31 was common among the selected South Indian caste groups (Dravidians). The haplotypes A33-B44 and A19-B35 were characteristic to Aryans while haplotypes A19-B22 and A19-B7 were characteristic to Dravidians. Further novel haplotypes such as A19-B14 and A33-B49 were unique to Parsis and Sourastran caste. A low frequency of A29 was observed among the A19 subtype repertoire. Prevalence of HLA A33 and A31 among North Indians (Aryans) and South Indians (Dravidians) along with their unique haplotypes may be a consequence of the founder effect, racial admixture or selection pressure due to environmental factors among this population.

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.

HLA class I antigen profile among Brahmins and related caste groups from Mumbai, Maharashtra, India.

Indian population is well known for its genetic diversity. Among the numerous endogamous communities which are restricted very much by custom, marriage and occupation, we have collected a total 157 individuals from1996-1999 comprising of Brahmins, Kunbis, Chandrasenia Kayastha Prabu (CKP), and Mahars caste groups. We present here the HLA antigen distribution of these endogamous caste groups and compare their distribution of HLA antigens with other caste groups reported from other parts of India. The HLA class I antigens were identified by using the standard complement mediated NIH microlymphocytotoxicity assay. The phenotype frequencies of HLA A2, B7, B27, B40, B52 in Kunbis, B35 in Brahmins, A9, A19, A11, B37, B16 in CKP and HLA A1, A2, A9, A19, B7, B35, B40, B53 in Mahars were found to be significantly increased. The phenotypic frequencies of HLA A3, B13, B17, B37 in Kunbis, A10, B8, B13, B18, B21, B37, B52, B57, B60 in Brahmins, A10, B8, B14, B21. B55, B53 in CKP and HLA A10, B8, 818, B22 in Mahars were significantly decreased among the HLA antigens tested. Two Locus haplotype analyses revealed that haplotype A10-B8 was common in Brahmins and Mahars while haplotype A19-B12 was common in Brahmins and CKP. Haplotypes A9-B15 and A3-B5 were identified only among the Brahmins. The other haplotypes were in concordance with the Indian haplotypes which have been commonly reported. The genetic distance analysis showed that the Brahmin community of Mumbai differs in their origin, migration and settlement, although they adopted Hinduism since ancient times. The observed antigen frequencies haplotype frequencies and linkage disequilibrium among the caste groups suggest the influence of genetic drift caused by selection, geography and culture. Further, the study reveals that the caste groups of India cannot be considered as a single panmictic population with reference to genetic characteristics which may have a clinical relevance in unrelated donor selection for allogenic Bone marrow transplantation in India.

Frequency and potential application of HLA antibodies from pregnant women in Mumbai.

Antenatal sera from 1334 pregnant women attending the Nowrojee B J Wadia Maternity Hospital and KEM Hospital in Parel, Mumbai were collected and screened for anti HLA A and B antibodies to produce an indigenous HLA tissue typing tray. One hundred and sixty three sera (12.2%) were found positive for HLA antibodies. Nonetheless, the percentage of positive sera were almost the same in women of different parity. Moreover, the incidence of anti-HLA antibodies was correlated with the allelic frequencies in the Maharastrian population. Thus in India, collection and screening of sera from pregnant females is a simple and cost-effective method of acquiring polyclonal sera for routine use in tissue typing.