Dear Sir. Concerning your issue about the application of HLA in pharmaceutical proteins. Genetic factors may modulate the immune response to a therapeutic protein product. In particular, some human leukocyte antigen (HLA) haplotypes may predispose patients to development of undesirable antibody responses to specific products (Hoffmann et al. 2008). If both appropriate and feasible, HLA mapping studies may help define a subset of the patient population at increased risk. Moreover, genetic polymorphisms in cytokine genes may up regulate or down regulate immune responses (Donnelly et al. 2011). Evaluation of genetic factors that may modulate the immune response to a therapeutic protein product is recommended in circumstances in which a subset of treated patients lose the clinical benefit of treatment or experience severe adverse events. For example, the subset of patients that generate neutralizing antibodies to IFN-beta products are more likely to possess distinct HLA haplotypes (Hoffmann et al. 2008). Thus, knowledge of the heightened susceptibility of patients with such HLA haplotypes may allow for measures to prevent such responses or for pursuit of other treatment options. The use of HLA transgenic mice in combination with the immune-tolerant models has been suggested to predict immunogenicity. HLA transgenic mice express human MHC and should in theory be able to present similar epitopes as patients. Combined transgenics expressing MHC and the human protein of interest might also be useful to answer the question whether the breaking of tolerance is restricted to certain HLA types. I think the following below links may help you in your analysis:

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm338856

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170476/

http://www.discoveryontarget.com/Membrane-Production/

https://www.google.ch/patents/EP2184070A1?cl=en

Thanks