HLA molecular mismatch algorithms and HLA-related immunological risk

HLA molecular mismatch algorithms and HLA-related immunological risk

Our lab has pioneered the development of computational algorithms (Cambridge HLA Immunogenicity algorithm and HLA Electrostatic Mismatch Score 3-Dimensional) to predict the immunogenic potential of donor HLA and provided evidence that this approach can be used as a prognostic biomarker of primary alloimmunity. We utilise diverse methodology including advanced computational tools (e.g. computational prediction of B- and T-cell epitopes, big data analyses of experimental and clinical datasets) and laboratory techniques (e.g. flow cytometry, Luminex, cytotoxicity assays, in vitro T- and B-cell assays, microfluidics). Our research has been recognised internationally and has led to numerous collaborations and active studies with transplant centres in Europe, the USA, and Australia. The overall aim of this programme of research is to improve donor-recipient HLA matching within organ allocation policies, enable better assessment of HLA-related immunological risk, and facilitate personalised immunosuppression management in transplant patients. 

Collaborations:NHS Blood and Transplant; the van der Schaar Lab, Cambridge, UK; Eurotransplant; University of Manitoba, Canada; Northwestern University, Chicago, USA; EMBL-EBI, Hinxton, UK; Kiel University, Germany. 

Key References

Kim JJ, Fichtner A, Copley HC, Gragert L, Susal C, Strologo LD, Oh J, Pape L, Weber LT, Weitz M, Konig JC, Krupka K, Tonshoff B, Kosmoliaptsis V. Molecular HLA mismatching for prediction of primary humoral alloimmunity and graft deterioration in paediatric kidney transplantation. Frontiers in Immunology 2023; 14: 1188527

Isaacson D, Schold JD, Gmeiner MW,Copley HC,Kosmoliaptsis V*, Tambur AR*. HLA-DQ Mismatches Lead to More Unacceptable Antigens, Greater Sensitization, and Increased Disparities in Repeat Transplant Candidates. JASN 2022; 33: 2293

Wiebe C, Kosmoliaptsis V, Pochinco D, Gibson IW, Ho J, Birk PE, Goldberg A, Karpinski M, Shaw J, Rush DN, Nickerson PW. HLA-DR/DQ molecular mismatch: A prognostic biomarker for primary alloimmunity. American Journal of Transplantation 2019; 19:1708

Mallon DH, Kling C, Robb M, Ellinghaus E, Bradley JA, Taylor CJ, Kabelitz D, Kosmoliaptsis V. Predicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electrostatic Potential. Journal of Immunology 2018; 201: 3780-3792

Kosmoliaptsis V, Sharples LD, Chaudhry AN, Halsall DJ, Bradley JA, Taylor CJ. Predicting HLA class II alloantigen immunogenicity from the number and physiochemical properties of amino acid polymorphisms. Transplantation 2011; 91: 183-90