Department of HLA and Transplantation

Projects

Completed projects  

1. Title: Production of HLA Cell tray from pregnant mother sera with a view to produce HLA Typing sera in India

Year of commencement: 1996-2000

Duration: 3 years

Funding agency: ICMR

Outcome: The arithmetic is as follows: Screen 1000 sera –> 100 to 150 have cytotoxic antibodies and –> 2 to 3 will be mono/duospecific HLA typing sera suitable for HLA typing.Therefore 1000 sera when screened will result into 2 or 3 potential sera, thus making this exercise labor intensive and a routine for every HLA laboratory

2. Title: HLA distribution in selected populations from Mumbai 13 th IHWC study.

Year of commencement: 2000-2002

Duration: 2 years

Funding agency: ICMR

Outcome: HLA allele distribution in different populations from Mumbai were revealed. Antigen frequencies, haplotype frequencies and linkage disequilibrium show immense heterogeneity and allele diversity among the caste and tribal groups.New allele subtypes such as A*2611N, A*0304 N etc have been observed and certain allele frequencies are very high B*1405 (Parsi) when compared to other world populations.

3. Title: PCR-SSP typing in Maratha caste from Mumbai

Year of commencement: 1999-2001

Duration : 3 years

Funding agency: ICMR

Outcome: The HLA DRB1 and DQB1 polymorphism in the Maratha caste group has been identified.

4. Title: Immunogentic and autoimmune studies on SLE patients from Mumbai.

Year of commencement: 1998-2000

Duration: 3 years

Funding agency: ICMR

Outcome: A Significant increase was observed in the frequency of HLA A1, A2, B27, DR3, DQB1*0302, DQB1*0601 among SLE patients. HLA A19, B15, DR7, DRB1* 14(6), DRB1*1001, DQB1*0203 were found to be decreased in the patient group compared to the controls (Table: 1). Table: 2 present the autoantibodies that were identified in the Major and Minor organ involved SLE patients studied. All the SLE patients with major organ involvement studied presented with high titer of ANF, AHA and anti -Sm antibodies.

5. Title: HLA matching and graft survival in cadaver renal transplants from Mumbai

Year of commencement: 1999-2001

Duration : 3 years

Funding agency: ICMR

Outcome: The cadaver transplant programs in Mumbai were not followed because of the availability of cadaver and other related problems. The number of cadaver transplantation was reduced. Moreover the follow up of the patients was not feasible because the patients were from remote areas. Therefore the cadaver transplants were not sufficiently available to continue this project. Therefore the project was not completed as it was expected.

6. Title: HLA B27 subtypes determination in seronegative spondarthritis (SSA) patients to assess their role in disease pathogenesis

Year of commencement: 2001-2003

Duration: 3 years

Funding agency: ICMR

Outcome: The HLA B27 allele will be initially determined on all the patients and controls using the standard two stage NIH micro lymphocytotoxicity assay. DNA extracted from all the serologically positive HLA B27 patients and controls will then be confirmed by polymerase chain reaction based sequence specific primer (PCR-SSP) using the commercial kit manufactured by BAG (histotype DNA-B27; Germany). Further the molecular subtypes will be genotyped for the currently defined 25 subtypes (B*2701-B*2725) of HLA B27 using the reverse line strip sequence specific oligo nucleotide probe hybridization (RLS-SSOP) class I kit (Dynal, Oslo, Norway).

7. Title: Concordance between serological and molecular HLA Typing strategies

Year of commencement: 2001-2003

Duration: 3 years

Funding agency: ICMR

Outcome: The serological technique will follow the standard NIH microlymphocytotoxicity assay for HLA A, B, C, DR and DQ loci using the commercially procured and as well as indigenously raised HLA antisera. The molecular DNA typing will follow the PCR-SSP (polymerase chain reaction with sequence specific primers) for HLA A, B, C, DRB, DRA, DQA, DQB, DPA and DPB using the commercially procured Ollerup PCR-SSP kits. The total genomic DNA will be extracted using the standard 12 th International Histicompatibility workshop protocol. The results will be evaluated for allele concordance in the serological and molecular techniques.

8. Title: Molecular and Clinical characterization of HLA B7 CREG and its comparison with HLA B27 associated SSA Patients

Year of commencement: 2004-2007

Duration: 3 years

Funding agency: ICMR

Outcome: HLA- B27 was found to be significantly associated with the SSA disease (AF = 20% vs. 2.2%; OR= 14.32; P value =8.89E-17) when compared to the controls. HLA- B7 (AF = 14.02% vs. 1.64%; O.R = 15.28; EF = 0.31; P value = 8.88E-09), HLA-B22 (AF = 3.77% vs. 1.97%; OR = 2.46; EF = 0.05; P value = 0.0504) and HLA-B40 (AF 3.61% vs. 5.75%; OR = 2.09; EF = 0.07; P value = 0.04) were significantly increased in the B27 negative group while HLA-B42 was not identified in either the groups. Two locus haplotype analyses revealed that haplotype A9-B27 (H.F.30.26%), A2-B27 (19.73%), A11-B27 (9.21%) and A3-B27 (20.39%) was common in HLA-B27 positive patient group.

9. Title: HLA associations among Recurrent spontaneous abortion patients

Year of commencement: 2004-2007

Duration: 3 years

Funding agency: ICMR

Outcome: Our analysis revealed that HLA A1, A3, A30 & B17 were increased while HLA A1, A3 and B17 were significantly increased, but HLA A9 decreased among the RSA patients from western India. A comparative analysis from reported world RSA patients revealed a differential association in our patients

10. Title: HLA associations in Vitiligo patients

Year of commencement: 2005-2007

Duration: 3 years

Funding agency: KEM (skin OPD) and NIIH

Outcome: Our results revealed that HLA A2, A11, A31, A33, B17, B35, B40 and B44 were increased while HLA A9, B13 and B53 were decreased in allele frequencies. Among the early onset vitiligo patients HLA A2, A33, B44 and B56 were significantly associated, while among patients with a familial history HLA A28, A31 and B44 were significantly associated. Vitiligo patients who had severe symptoms (>10% body involvement) showed a significant association of HLA A10 and B8.

11. Title: HLA associations in Ulcerative colitis patients

Year of commencement: 2005-2007

Duration: 2 years

Funding agency: KEM (gastroenterology) and NIIH

Outcome: HLA Aw19 was associated with Ulcerative colitis. Further HLA A*3303 subtype was associated in severe patients from Western India.

12. Title: HLA studies in Psoriasis patients from Mumbai.

Year of commencement: 2006-2007

Duration: 1 year

Funding agency: KEM (skin OPD) and NIIH

Outcome: The HLA alleles associated with psoriasis have been revealed.

13. Title: HLA distribution in HIV positive sero-discordant couples from Manipur.

Year of commencement: 2006-2009

Duration: 3 years

Funding agency: NACO

Expected Outcome: The HLA alleles involved in serodiscordant couples will be revealed.

14. Title: HLA studies in Asthma patients from Western India.

Year of commencement: 2007-2009

Duration : 3 years

Funding agency: ICMR

Ongoing Projects:

1. Title: HLA studies in autoimmune associated RApatients from Mumbai.

Year of commencement: 2010-2011

Duration: 1 year

Funding agency: KEM (ortho OPD) and NIIH

Outcome: The HLA alleles associated with autoimmune associated RA will be revealed.