Examine Human Leukocyte Antigen, Killer-cell Immunoglobulin-like Receptor Genomics

If you can propose research to investigate the relationship between genetic variation in human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) region genomics and immune-mediated diseases, consider applying to NIAID’s notice of funding opportunity (NOFO) Human Leukocyte Antigen (HLA) and Killer-cell Immunoglobulin-like Receptor (KIR) Region Genomics in Immune-Mediated Diseases (U01, Clinical Trial Not Allowed). 

The NOFO seeks applications to join the HLA and KIR Region Genomics in Immune-Mediated Diseases Consortium (HLA and KIR RGC) that meet the following objectives: 1) define associations between variations in HLA and KIR genomic regions and immune-mediated diseases; 2) uncover mechanisms underlying those associations with the goal of advancing therapeutic opportunities, and 3) validate association data in order to improve predictive power of clinical disease screening.  

To support these goals, the HLA and KIR RGC will continue to develop and utilize cutting-edge technologies and analysis pipelines to generate high quality HLA and KIR sequences and disease association data for submission to the Immunology Database and Analysis Portal (ImmPort) and, when appropriate, publicly accessible databases such as the Database of Genotypes and Phenotypes (dGaP) or Immuno Polymorphism Database (IPD).  

This initiative will support prospective or retrospective studies that investigate the relationship between genetic variation in HLA and KIR genomic regions and immune-mediated diseases, including susceptibility to or protection from disease onset, progression, and severity. Studies must focus on identifying novel associations with high resolution or validating previously described associations.  

Examples of possible research areas include: 

• Acute or chronic transplant rejection, including the influence of donor/recipient matching on outcomes following solid organ or pancreatic islet transplantation, e.g., studies that explore the mechanisms underlying the observed association of outcomes with eplet matching scores (HLAmM).  
• Graft-versus-host disease following bone marrow transplantation. 
• Autoimmune diseases mediated by HLA and KIR genomic regions. 
• Neuro-immune and neuropsychiatric diseases and syndromes. 
• Allergy, including asthma and responses to environmental or food allergens. 
• Vaccines, post-COVID conditions, post-vaccine Guillian-Barre Syndrome. 
• Immune-mediated diseases, including outcomes of organ transplantation, disproportionately prevalent or severe in specific racial, ethnic, or gender groups, especially minority populations. 
• Development or refinement of sequencing technologies and analytical tools to improve the identification, validation, or prediction of relative disease risk. 
• Studies of HLA-KIR region gene combinations. 
• Mechanistic studies that explore the molecular consequences of specific polymorphisms within HLA and KIR genomic regions on disease phenotype. 

NIAID will consider applications that propose the following types of studies to be nonresponsive and not review them: 

• Type 1 diabetes association studies. 
• Infectious disease and vaccine response association studies that are not performed in the context of subsequent development of immune-mediated disease. 
• Cancer association studies. 
• Animal studies, unless designed to support mechanistic evaluation of defined human disease associations. 
• Population diversity studies, unless performed in relation to immune-mediated disease prevalence or severity. 
• Clinical trials. 
• Serology-based HLA or KIR typing projects. 
• HIV/AIDS association studies. 
• Projects focused on drug development. 
• Mechanistic projects focused on animal models. 
• Projects that do not include a focus on identifying novel associations with high resolution or validating previously described associations and the associated clinical phenotype data. 

Your research plan must include a realistic timeline for completing study aims and list explicit and quantitative annual milestones, which NIAID program staff will use to assess annual progress and support funding decisions. We strongly encourage applicants to contact the scientific research contacts listed in the NOFO prior to applying to discuss the proposed research program.  

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), submitted as Other Project Information as an attachment (see Section IV). Applicants should read the instructions in the NOFO and review the available PEDP guidance material carefully. Peer reviewers will assess the PEDP as part of the scientific and technical peer review evaluation; NIAID staff will also consider it alongside programmatic matters with respect to funding decisions. 

You must also submit a Data Management and Sharing Plan. As noted above, award recipients will share their data publicly through ImmPort or other public portals approved by NIH. Therefore, be sure to include a summary of how you will manage data submission and interactions with ImmPort as part of your Data Management and Sharing Plan.

Award and Deadline Information 

NIAID plans to fund three or four awards in fiscal year 2025. Application budgets are not expected to exceed $400,000 in annual direct costs and should reflect the actual needs of the proposed project. 

The scope of the proposed project should determine the project period. The maximum project period is 5 years. 

Applications are due by August 20, 2024, at 5:00 p.m. local time of the applicant organization.