Transplant Immunology & Immunogenetics

• Low resolution HLA typing by Sequence specific primer (SSP) method
• Low resolution HLA typing by Sequence specific oligonucleotide probe (SSO) method
• High resolution sequence based HLA typing by Sangers Sequencing method (SBT)
• High resolution sequence based HLA typing by Next Generation Sequencing (NGS) method
• Killer Cell Immunoglobulin Receptor (KIR) genotyping by Sequence specific primer (SSP) method

• HLA DRB1*15- Cyclosporine/Tacrolimus
• HLA B*58:01- Allopurinol
• HLA B*57:01- Abacavir
• HLA B*13:01- Dapsone
• HLA A*31:01- Carbamezapine
• HLA B*15:02- Phenytoin

• HLA B*27 Ankylosing Spondylitis
• HLA B*51 Behcets Disease
• HLA DRB*1 Rheumatoid Arthritis

• HLA G*

• Donor Specific Antibody (DSA) Assay
• Single Antigen Bead based assay using Luminex technology for HLA Class I and Class II antigens.
• Single Antigen Bead based assay using Luminex technology for C3d compliment binding antibody [C3d Single Allele Antibody Class I & II]
• Panel Reactive Antibody (PRA) Screen using Luminex technology [Pre and Post Transplantation]

In addition to the services described above for transplant patients, HLA testing for the following conditions are also performed:

• Platelet transfusion support: Patients with low platelet counts are at risk for serious bleeding complications and are often transfused with platelets from healthy donors. However, patients can sometimes produce antibodies to the HLA molecules expressed on platelets, which reduce the effectiveness of platelet transfusion. HLA typing and antibody detection help physicians choose a platelet donor that will result in increased platelet counts for patients in need.

The TII laboratory runs Ph.D. degree program affiliated to the Homi Bhabha National Institute (HBNI). An aided institution of the Department of Atomic Energy and a deemed to be university under section 3 of the UGC Act. The information and due procedure of application can be obtained from “Academic and Project Cell”, ACTREC Email: tii.hla@actrec.gov.in and Tel: Contact Tel: 022 6873 5000 (Ext. 5828/5820).

Orientation program is conducted at TII for Fellows, DM students from Medical Oncology and Transfusion Medicine.

The lab also offers short term research projects (dissertation) for Mumbai University and other universities M.Sc. /M. Tech/B. Tech programs. Contact Tel: 022 6873 5000 (Ext. 5828/5820) 15 days to 1 month Observer ship is offered to medical post-graduates, scientists, science post-graduates from India and from other countries as well under the scope cell. Contact Tel: 022 6873 5000.(Ext. 5828/5820).

The laboratory conducts research primarily focused on improving the methods/ techniques for donor selection/screening and also for developing an algorithm for donor selection, with regular publications in national and international peer reviewed journals. The Laboratory staff participates in conferences and education programs thereby fostering greater awareness levels among staff. The research area is broadly focused on the various aspects of Transplant Immunology & Immunogenetics with relation to various hemato-lymphoid and solid organ transplants. The lab also focuses on translational research using molecular, proteomics, etc. techniques in developing Lab-to-Clinic oriented novel assays with implications in the diagnosis and prognosis of transplant patients resulting in better treatment outcomes and patient care. Pharmacogenomics and disease association in relation to HLA is also being explored.

The lab has various ongoing research projects focussed on improving HLA diagnostics as well as exploring adoptive cellular therapies for leukemic patients.

• Molecular studies
The research under this area are:
1. Non HLA genes associated with allogeneic hematopoietic stem cell transplantation This project is aimed at screening Killer immunoglobulin like receptor genes, polymorphisms within the cytokine and chemokine genes, immune reconstitution profile of the patient at baseline and follow up and correlate them with HSCT outcomes
2. Impact of HLA typing resolution on donor selection and transplant outcomes in matched Allogeneic Hematopoietic Stem Cell Transplantation.
   The aim of this project is to evaluate the role of high resolution HLA typing in predicting HSCT outcomes.
3. Interaction of Vitamin D Receptor gene polymorphism with HLA alleles and its correlation with immune modulation affecting graft outcomes and survival in HLA matched sibling allogeneic stem cell transplantation. This study is planned to investigate the relationship between VDR gene polymorphisms, Vit. D levels pre transplantation and the transplant outcomes in HLA matched HSCT.
• Immunotherapy focussed studies
The ex-vivo and in-vivo research on “adoptive cell immunotherapy” like Virus-specific T-cell (VSTs) and NK cell immunotherapy in Allogeneic-HSCT has been a focus of our lab. The projects under this area of research are:
1. Generation and Characterization of third party donor derived AdV, CMV and EBV multivirus specific T cells for therapeutic intervention in patients undergoing Hematopoietic Stem Cell Transplantation
   Through this project we aim to generate multivirus (AdV, CMV, and EBV) specific T cells which could then be scaled up to GMP and infused in leukemic patients who encounter such viral infections.
2. Implications for NK Immunotherapy: Killer Immunoglobulin like receptor-Human Leukocyte Antigen ligand match/mismatch in post cyclophosphamide T cell replete haploidentical/mismatched HSCT outcomes in AML
   This is a proof of concept project where we are aiming to prove the NK cell cytotoxicity based on the KIR receptor-ligand match/mismatch hypothesis. We will also be looking at the KIR profile pre and post HSCT to look at the functional NK cells being reconstituted. This project will serve as a base for scale up to NK immunotherapy.

The lab participated in the following components of the workshop:

1. Population genetics, anthropology and evolution
   For this component, the lab performed high resolution (NGS) HLA typing for 11 loci in 184 unrelated healthy donors from India. A total of 25 novel alleles were observed, which have been added to the IMGT database and have been published in the peer reviewed HLA journal (Impact Factor 9.2)
2. High-resolution KIR in populations
   As part of this component, KIR high resolution typing (NGS) was conducted for the KIR inhibitory genes in 120 unrelated healthy donors from India. This is the first data from Indian population.

1. Andrea S. Pinto, Jyoti Rajak, Manisha Tambe, Selma Z. D'Silva, Meenakshi Singh Identification of the novel HLA-A*01:01:01:111 allele in two individuals from Uttar Pradesh, India DOI: https://doi.org/10.1111/tan.15021


2. Jyoti Rajak, Andrea S. Pinto, Selma Z. D'Silva, Meenakshi Singh Identification of the HLA-B*40:01:02:59 and -C*05:01:73 alleles in individuals from the northern regions of India DOI: https://doi.org/10.1111/tan.15030


3. Selma Zenia D’Silva, Anand Bodade, Shalaka Kadam, Manisha Tambe, Sandeep Dhanda ·Bhausaheb Bagal, Manju Sengar, Hasmukh Jain, Lingaraj Nayak, Avinash Bonda, Sachin Punatar, Anant Gokarn, Navin Khattry, Meenakshi Singh, Frequency of HLA alleles and KIR Ligands in Acute Myeloid Leukemia in Indian Cohort DOI: 10.1007/s12288-022-01550-0


4. Bansi S. Parsaniya, Andrea S. Pinto, Manisha Tambe, Selma Z. D'Silva, Meenakshi Singh Identification of the novel HLA allele, HLA-DRB1*14:245, in an individual from Northern India DOI : https://doi.org/10.1111/tan.14784


5. Andrea S. Pinto, Manisha Tambe, Selma Z. D'Silva,Meenakshi Singh Identification of the novel HLA-B*51:01:01:108 allele and confirmation of HLA-B*40:387 in two Indian individuals DOI : https://doi.org/10.1111/tan.14785


6. Bansi S. Parsaniya, Manisha Tambe, Selma Z. D'Silva, Meenakshi Singh Identification of the HLA-A allele, HLA-A*11:03:01:02, in two individuals in a Western Indian family DOI: https://doi.org/10.1111/tan.14787


7. Selma Z. D'Silva, Manisha Tambe, Andrea S. Pinto, Meenakshi Singh The novel HLA-B*52:01:01:23 allele in an individual from Uttar Pradesh, North India DOI : https://doi.org/10.1111/tan.14812


8. Jyoti Rajak, Manisha Tambe, Selma Z. D'Silva, Meenakshi Singh Identification of the novel HLA-DPA1*02:82 allele in a Punjabi individual DOI:https://doi.org/10.1111/tan.14805


9. Andrea S. Pinto, Manisha Tambe, Selma Z. D'Silva, Meenakshi Singh Identification of the novel HLA-DQB1*06:01:01:04 allele in an individual from Western India DOI : https://doi.org/10.1111/tan.14809


10. Selma Z. D'Silva, Manisha Tambe, Andrea Pinto, Meenakshi Singh Identification of the novel HLA-DQB1*04:02:01:18 allele in a Maharashtrian individual from India DOI: https://doi.org/10.1111/tan.14789


11. Manisha Tambe, Selma Z. D'silva, Andrea S. Pinto, Bansi Parsaniya, Meenakshi Singh Identification of the novel allele, HLA-A*02:11:01:06, in two North Indian individuals in a Kshatriya family DOI: https://doi.org/10.1111/tan.14814


12. Selma Z. D'Silva, Manisha Tambe, Andrea S. Pinto, Meenakshi Singh Identification of the novel allele, HLA-C*06:02:38:02, in a Gujarati individual from India DOI: https://doi.org/10.1111/tan.14813


13. Manisha Tambe, Selma Z. D'Silva, Bansi Parsaniya, Andrea S. Pinto, Meenakshi Singh Identification of HLA-C*03:599 novel allele variant in two South Indian individuals in a Brahmin family DOI: https://doi.org/10.1111/tan.14815


14. Bansi S. Parsaniya, Andrea S. Pinto, Selma Z. D'Silva, Meenakshi Singh Characterization of the novel HLA allele, HLA-C*07:04:01:19, in an individual from Maharashtra, India DOI : https://doi.org/10.1111/tan.14825


15. Andrea S. Pinto, Manisha Tambe, Selma Z. D'Silva,Meenakshi Singh Identification of the novel HLA-C*12:02:47 allele in an individual from Maharashtra, India DOI : https://doi.org/10.1111/tan.14826


16. Andrea S. Pinto, Manisha Tambe, Selma Z. D'Silva, Meenakshi Singh Identification of the novel HLA-DQA1*01:01:01:10 allele in an individual from Orissa, India DOI : https://doi.org/10.1111/tan.14836


17. Manisha Tambe, Selma Z. D'Silva, Jyoti Rajak, Andrea S. Pinto, Meenakshi Singh The novel HLA-B*40:02:01:39 allele in an individual from a Kshatriya family in North India DOI : https://doi.org/10.1111/tan.14849


18. Manisha Tambe, Selma Z. D'Silva, Andrea S. Pinto, Meenakshi Singh Characterization of the novel HLA-B*58:01:01:19 allele by next-generation sequencing DOI: https://doi.org/10.1111/tan.14850


19. Andrea S. Pinto, Manisha Tambe, Selma Z. D'Silva,Meenakshi Singh Identification of the novel HLA-DPA1*01:03:01:64 allele in an individual from Uttar Pradesh, India DOI: https://doi.org/10.1111/tan.14857


20. Manisha Tambe, Jyoti Rajak, Andrea S. Pinto, Selma Z. D'Silva,Meenakshi Singh Identification of the novel HLA allele, HLA-B*37:01:01:19, in an individual from northern India DOI: https://doi.org/10.1111/tan.14860


21. Manisha Tambe, Selma Z. D'Silva, Andrea S. Pinto, Meenakshi Singh Identification of the novel HLA-C*07:02:01:184 allele in an Indian individual from a Kshatriya family DOI : https://doi.org/10.1111/tan.14865


22. Tenzin Phuntsok, Jyoti Rajak, Selma Z. D'Silva, Manisha Tambe, Meenakshi Singh. Characterization of the novel HLA-B*51:01:01:83 allele in three individuals from North India. 06 October 2021,HLA DOI: https://doi.org/10.1111/tan.14446


23. Jyoti Rajak, Selma Z. D'Silva, Manisha Tambe, Tenzin Phuntsok, Meenakshi Singh. Identification of a novel HLA-DPB1*02:01:61 allele in an Indian individual. 06 October 2021, HLA DOI: https://doi.org/10.1111/tan.14445


24. Tenzin Phuntsok, Manisha Tambe, Selma Z. D'Silva, Jyoti Rajak, Meenakshi Singh. Characterization of novel HLA-B*13:02:01:18 allele in a North Indian individual. 06 October 2021, HLA DOI: https://doi.org/10.1111/tan.14443


25. Tenzin Phuntsok, Selma Z. D'Silva, Manisha Tambe, Jyoti Rajak, Meenakshi Singh.Characterization of the novel HLA‐B*52:01:01:18 allele in a West Indian individual. 06 October 2021, HLA DOI: https://doi.org/10.1111/tan.14448


26. Tenzin Phuntsok, Selma Z. D'Silva, Manisha Tambe, Meenakshi Singh. Identification of the novel HLA-B*35:03:01:22 allele in an individual of Nepalese origin. July 2021, HLA DOI: https://doi.org/10.1111/tan.14353


27. Selma Z. D'Silva, Manisha Tambe, Jyoti Rajak, Tenzin Phuntsok, Meenakshi Singh. Identification of the novel HLA-C*14:02:01:22 allele in an Indian individual. July 2021, HLA DOI: https://doi.org/10.1111/tan.14352


28. Selma Z. D'Silva, Tenzin Phuntsok Manisha Tambe, Jyoti Rajak, Meenakshi Singh. Identification of a novel HLA-A*24 allele, A*24:537, identified in three individuals in an Indian family. July 2021, HLA DOI: https://doi.org/10.1111/tan.14355


29. Manisha Tambe, Tenzin Phuntsok, Selma Z. D'Silva, Jyoti Rajak, Meenakshi Singh. Characterization of a novel HLA‐C *04:01:01:102 allele in an individual from West Bengal. July 2021, HLA DOI: https://doi.org/10.1111/tan.14363


30. Mohapatra S, Menon NG, Mohapatra G, Pisharody L, Pattnaik A, Menon NG, Bhukya Prudhvi Lal, Srivastava M, Singh M, Barman MK, Gin KY, Mukherji S. The novel SARS-CoV-2 pandemic: Possible environmental transmission, detection, persistence and fate during wastewater and water treatment. Sci Total Environ. 2020 Oct 6:142746. PMID: 33092831; PMCID: PMC7536135. DOI: https://doi.org/10.1016/j.scitotenv.2020.142746


31. D’Silva SZ, Dhanda SK, Singh M. Killer immunoglobulin like receptor gene profiling in Western Indian population. Hum. Immunol. 2019; (19): 30206.


32. D’Silva SZ, Punatar S, Gokarn A, Bonda A, Tambe M, Matthew L, Kannan S, Khattry N, Singh M. Implication of patient KIR ligands and donor KIR genotypes on transplant outcomes in T cell replete haploidentical transplant with post-transplant cyclophosphamide.


33. D’Silva SZ, Dhanda SK, Rajadhyaksha SB., Khattry N, Singh M. Diversity of Killer Immunoglobulin like receptor genes, alleles, and their genotypes among the Western Indian population. Genetic Testing and Molecular Biomarkers.


34. Sharma S, Sharma U, Chaudhary A, Naithani M, Naithani P, Prashar S, Sharma B, Nagar PK,Bhukya PL, Bhalerao U, Singh M. , Srivastava M, Barman MK, Attri S, Gairolla J. SARS-CoV-2:Insights from the Immunopathogenesis and Current Clinical Diagnosis and Therapeutic Strategies. J Immunological Sci. (2021); 5(2): 1-15

The lab is aiming forward to setting up HLA epitope match platelet donor registry which will serve platelet refractory patients of our centre.