Advancing Autoimmune Disease Research: Integrating Genetic, Environmental, and Immunological Factors to Improve Diagnosis and Treatment (Highlighted Topic)

Advancing Autoimmune Disease Research: Integrating Genetic, Environmental, and Immunological Factors to Improve Diagnosis and Treatment (Highlighted Topic) is sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and other NIH Institutes, Centers, and Offices (ICOs). Advancing Autoimmune Disease Research: Integrating Genetic, Environmental, and Immunological Factors to Improve Diagnosis and Treatment (Highlighted Topic) is sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and other NIH Insti…

Advancing Autoimmune Disease Research: Integrating Genetic, Environmental, and Immunological Factors to Improve Diagnosis and Treatment | Grants & Funding U.S. Department of Health and Human Services National Institutes of Health Advancing Autoimmune Disease Research: Integrating Genetic, Environmental, and Immunological Factors to Improve Diagnosis and Treatment When beginning your next investigator-initiated application, consider the following NIH highlighted topic.

The area of science described below is of interest to the listed NIH Institutes, Centers, and Offices (ICOs). This is not a notice of funding opportunity (NOFO). Apply through an appropriate NIH Parent Funding Announcement or another broad NIH opportunity available on Grants.

gov . Learn how to interpret and use Highlighted Topics . Expiration Date: February 12, 2028 Autoimmune diseases include more than 140 different diseases and conditions and are among the most common chronic diseases in the U.S., impacting 23.

5–50 million people. A common feature of many autoimmune diseases is a period of asymptomatic autoimmunity known as the prodrome, often manifested by the development of autoantibodies and other markers of immune activation. People living with one autoimmune disease have a high likelihood of developing additional autoimmune diseases, suggesting commonalities in disease pathogenesis and shared risk factors that predispose to autoimmunity.

Although many autoimmune diseases occur in genetically susceptible individuals, genetics alone cannot explain the rapidly increasing incidence and prevalence of autoimmune diseases. The exposome, which encompasses the many exposures experienced by humans throughout their lives, is thought to contribute to the risk of autoimmunity, but the study of exposures is challenging because of exposure latency and spatiotemporal variability.

Additionally, exposures may have different influences depending on the life stage of the individual. Accelerating scientific understanding of autoimmune disease development, progression, and impact across all aspects of daily life is essential to advancing this field.

Integrating exposome research into longitudinal and cross-sectional studies, from before disease becomes manifest through the course of disease, will be vital to understand the role of the immunome in the matrix connecting exposures and genetic risk in autoimmunity.

The purpose of this topic is to advance scientific understanding of autoimmune disease development, progression, and impact, and to improve health outcomes for those affected. We are seeking research projects that: Harness computational tools and collaborative networks to investigate protective and driving factors of pre-clinical autoimmunity, disease inception, and flares in human cohorts.

This may include studying the interplay of genetics, immunome, and the exposome across the lifespan. Advance diagnostic testing, biomarkers, predictive models, and technologies (e.g., point-of-care testing, imaging, sensors, wearables) for autoimmune diseases.

Develop novel research models, including New Approach Methodologies (NAMs), that help explore shared mechanisms across co-occurring and discrete autoimmune disorders and the prodromal phase of autoimmunity.

Central Scientific Contact: Victoria Shanmugam, MBBS, FRCP, FACR, CCD Office of Research on Women's Health (ORWH) The Office of Autoimmune Disease Research in the Office of Research on Women’s Health (OADR-ORWH) is interested in all the exemplary topics above, with a particular focus on addressing current gaps in the autoimmune disease research portfolio.

Topics of interest include: prodromal stage of autoimmunity less-studied autoimmune diseases in the portfolio co-occurring autoimmune diseases epidemiology of autoimmunity development and adoption of common data elements for autoimmune disease research sex-specific variation across autoimmune diseases The engagement of people living with and at risk of autoimmunity, family members/loved ones, clinicians, and allied health professionals in applications is strongly encouraged to ensure research has direct relevance to human health.

This office does not award grants. Applications must be relevant to the objectives of at least one of the participating NIH Institutes and Centers listed in this topic. Victoria Shanmugam, MBBS, FRCP, FACR, CCD National Cancer Institute (NCI) NCI encourages research at the intersection of autoimmunity and cancer immunology.

Defects in immune surveillance contribute to tumor progression, while breakdown of tolerance leads to autoimmunity. Cancer immunotherapies enable dramatic anti-tumor immune responses. However, all immunotherapy modalities can lead to autoimmune, immune-related adverse events (irAEs), which can be life threatening.

Similarly, immunosuppressive therapy for autoimmune disease is a risk factor for malignancy.

NCI research may include, but are not limited to: Interrogating immune mechanisms at the intersection of anti-tumor immunity and autoimmunity and/or irAEs; Developing model systems (pre-clinical, in vitro tissue, in silico, computational, synthetic and/or engineered models, etc.) to study the cancer-autoimmunity connection and/or irAEs; Investigating role(s) of metabolism, diet, exercise, microbiome, exposome, aging or other co-morbidities modulating the cancer-autoimmunity connection and/or irAEs Lillian Kuo, Ph.

D. (immune mechanisms, intersection of cancer and autoimmunity) Yin Liu, Ph. D.

(immune-related adverse events from cancer immunotherapy) National Eye Institute (NEI) NEI encourages innovative research to advance scientific understanding, diagnosis, and treatment of ocular autoimmune diseases, including but not limited to autoimmune uveitis, pars planitis, sympathetic ophthalmia, autoimmune retinopathy, Sjogren’s syndrome, and scleritis.

Areas of interest include: Mechanisms of ocular autoimmune disease development and progression Partnerships with researchers studying extra-ocular autoimmunity to advance discovery by leveraging and identifying shared disease mechanisms Novel alternative methods (NAM) models that faithfully recapitulate human ocular autoimmune diseases to improve diagnosis and treatment Advancement of molecular and bioinformatic discovery tools, biomarkers, predictive models, and technologies Collaborative networks, clinical research, and other epidemiological studies to improve health outcomes Training next generation researchers and clinicians in the field of ocular autoimmune diseases Nataliya Gordiyenko, Ph.

D. National Human Genome Research Institute (NHGRI) NHGRI supports studies that provide generalizable methods and knowledge. Studies of genomic influences on autoimmunity that are comprehensive across the genome or are generalizable across variants, tissues, diseases, or function may be in scope for NHGRI.

The development of novel computational, bioinformatic and analytical approaches to analyze and integrate multi-modal data that are broadly applicable to a variety of autoimmune diseases and beyond are also of interest. Applications for studies relevant only to a particular disease or organ system should be directed to the appropriate Institute or Center.

Applications whose primary scientific objective is to understand a single biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention, will not be in scope for NHGRI.

National Heart, Lung, and Blood Institute (NHLBI) NHLBI encourages investigator-initiated proposals that advance the understanding, diagnosis, and treatment of autoimmune diseases relevant to heart, lung, blood, and sleep disorders, implementation science, and community-engaged research.

Potential areas of interest include, but are not limited to: • Prioritizing research into fundamental mechanisms driving autoimmune diseases and identifying biomarkers for early detection and disease progression. • Optimizing research models that accurately reflect human autoimmune diseases and translating basic science findings into the clinic for predictive modeling and early intervention.

• Leveraging existing cohort studies for identifying genetic, environmental, and microbiome risk factors contributing to autoimmune diseases. • Development and evaluation of novel therapies. • Testing implementation strategies to increase adoption, sustainment, or spread evidence-based interventions for heart, lung, blood, or sleep disorders.

National Institute on Aging (NIA) National Institute on Aging (NIA) is interested in supporting projects that advance our knowledge of immune function during aging and development of chronic diseases. These include but are not limited to: Impact of immune aging (immunosenescence) and inflammaging in the development and progression of autoimmune diseases, and impact of autoimmune diseases on accelerated aging (immune aging).

Research on multimorbidity – the intersection of autoimmune diseases with other types of chronic age-related conditions – in older adults including epidemiological, biological, and societal impacts.

Research on impact and influence of autoimmune conditions on trajectories of brain aging and risk of Alzheimer’s Disease and related dementias (ADRD), etiology, prevention, and responsiveness to pharmacologic and non-pharmacologic intervention.

National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institute on Alcohol Abuse and Alcoholism (NIAAA) NIAAA is interested in human data regarding any interaction of alcohol exposure on the incidence or manifestation of autoimmune diseases.

National Institute of Allergy and Infectious Diseases (NIAID) NIAID supports immunology research on the development and progression of autoimmune disease; improved diagnosis; and rational selection or development of therapies to prevent, delay or effectively treat autoimmune disease.

Examples of areas of interest include: Immune mechanisms associated with disease development, progression, outcomes, and success/failure of therapeutics Common mechanisms/endotypes associated with multiple autoimmune diseases Role of mucosal immunity, the neuroimmune axis or other organ systems on development, progression, or protection from autoimmune diseases Identification of inborn errors of immunity associated with autoimmune diseases The role of microbial exposures or infection on disease development The role of tissue-resident cells on development of autoimmune diseases Clinical trials with integrated mechanistic studies designed to explore the immunological basis of disease and mechanisms of action of therapeutics Mireia Guerau, Ph.

D. (for non-clinical applicants) Stacy Ferguson. Ph.

D. (for non-clinical applicants) Patricia Rohan, M. D.

(for clinical trials and NIAID’s expectations) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) NIAMS seeks research projects that advance the goals of this topic and are relevant to autoimmune diseases and conditions within the mission of the NIAMS. IC may give special consideration to support meritorious applications in this topic area.

National Institute of Biomedical Imaging and Bioengineering (NIBIB) NIBIB has an interest in technology development for diagnosing, monitoring, and treating autoimmune diseases; projects primarily focusing on mechanistic understanding of autoimmunity will not be supported.

Potential NIBIB projects for autoimmune research include but are not limited to: point-of-care technologies, wearables, bioanalytical sensors, mobile and digital health, computational tools for image and data analysis, AI/ML technologies, high-throughput and screening tools, digital twins technical development of MRI, ultrasound, PET, CT, optical imaging, and molecular probes for non-invasive visualization of immune activity, inflammation, tissue damage, and disease progression of autoimmune diseases tools for DNA manipulation, cellular/tissue engineering for disease detection or immunotherapy novel nanomaterials, biomimetic matrices, engineered viruses, EVs bioelectronics, bioelectromagnetic devices, wearables for disease monitoring, exoskeletons for therapeutic interventions Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) NICHD encourages applications relevant to NICHD's priority populations, including children, adolescents, and persons with disabilities.

NICHD is particularly interested in research addressing the Institute’s priorities and strategic goals. Interests include but are not limited to: Studies focused on the etiology, pathophysiology, diagnosis, or treatment of endometriosis, including the causal link between endometriosis and other autoimmune conditions. Autoimmune conditions in reproductive health.

Studies on placental transport of immunosuppressive medications, including research to minimize drug transmission to the fetus. Autoimmune conditions during pregnancy or impact on mother/infant outcomes. Autoimmune conditions in children, particularly if not within the mission of other ICOs.

National Institute on Deafness and Other Communication Disorders (NIDCD) National Institute on Deafness and Other Communication Disorders(NIDCD): NIDCD is interested in receiving research applications to better understand autoimmune inner ear disease (AIED); also known as autoimmune-associated sudden sensorineural hearing loss (SSNHL). AIED is an inflammatory disorder of the inner ear.

It typically presents with unilateral sudden sensorineural hearing loss that can rapidly progress to involve the second ear. The sudden hearing loss may be fluctuating or progressive. The overall research goal should be to develop strategies to prevent and treat this disease.

Applications focused on other forms of sensorineural hearing loss will be considered non-responsive. National Institute of Dental and Craniofacial Research (NIDCR) NIDCR encourages basic and translational studies of autoimmune diseases of the oral cavity, and manifestations of systemic autoimmune diseases in dental, oral and craniofacial (DOC) tissues that affect oral health outcomes.

Research may include, but is not limited to: Defining, and characterizing the mechanistic role of exposures in immunome/genomic processes in DOC autoimmune conditions and oral health endpoints of systemic autoimmune diseases Linking of oral health measures to exposure studies to enhance DOC autoimmune studies across lifespan Extending the use of exposomic models to DOC autoimmune and inflammatory conditions of the oral cavity Validating the use of NAMs, computational models, and predictive technologies to analyze the influence of exposomic factors on autoimmune manifestations in DOC tissues Investigating how biological variables alter the risk for autoimmune manifestations and influence varying outcomes in DOC conditions due to exposures across lifespan National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) NIDDK seeks research projects in autoimmune diseases to advance: Computational tools and collaborative networks to investigate protective and driving factors of pre-clinical autoimmunity, disease inception, and flares in human cohorts, including the interplay of genetics, immunome, and the exposome across the lifespan.

Diagnostic testing, biomarkers, predictive models, and technologies (e.g., point-of-care testing, imaging, sensors, wearables). Research models, including New Approach Methodologies (NAMs), to study co-occurring and discrete disorders and the prodromal phase.

Mechanistic, preclinical and clinical research in Crohn’s disease and ulcerative colitis, celiac disease, microscopic colitis, autoimmune hepatitis and pancreatitis, primary biliary cholangitis, Research in glomerular, tubular, and other kidney diseases, and urologic and benign hematologic systems. IC may give special consideration to support meritorious applications in this topic area. Guillermo A.

Arreaza-Rubín, M. D. Primary Contact and Diabetes, Endocrinology & Metabolic Diseases Stephen P.

James, M. D. Digestive Disease and Nutrition Debbie Gipson, M.

D. , M. S.

, Kidney, Urology, & Hematological Diseases National Institute of Environmental Health Sciences (NIEHS) NIEHS is interested in epidemiology, mechanistic (including toxicology and New Approach Methodologies [NAMs]), and computational studies that examine the role of the exposome/environmental exposures in the development and/or progression of autoimmune diseases.

National Institute of Mental Health (NIMH) NIMH is interested in supporting research aimed at advancing the understanding of the relationship between autoimmune processes and mental disorders with emphasis on Pediatric Autoimmune Neuropsychiatric Disorder Associated with Group A Streptococci (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS).

Increasing the knowledge of causative link between autoantibodies against central nervous system (CNS) antigens and neuropsychiatric symptomatology is needed to advance the diagnosis, treatment and improve quality of life in these conditions.

Within the scope of this topic, the NIMH is interested in research unveiling common and divergent genetic risk, research of the targets and downstream process in the CNS impacted by autoantibodies and cross-reactive antibodies, co-occurrence of autoimmune and mental disorders and interactions with the exposome.

National Institute on Minority Health and Health Disparities (NIMHD) The incidence, prevalence, and morbidity of autoimmune diseases varies across U.S. regions and among populations experiencing health disparities, possibly due to interacting social, biological, behavioral, and/or health care factors that contribute to poor outcomes.

Characterize mechanisms of autoimmune disease disparities that may exist in various geographic regions in the US and among specific populations.

Utilize an exposomic approach to evaluate multiple exposures in the built and natural environments on autoimmune disease outcomes Evaluate how biological (e.g., genomic, immunological), social, community, and healthcare factors interact and contribute to risk and outcomes across populations Utilize AI/ML and data science tools to understand causes for, and develop solutions to, health disparities in autoimmune disease Develop tailored interventions to reduce health disparities in autoimmune disease National Institute of Neurological Disorders and Stroke (NINDS) The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease for all.

NINDS supports basic disease, translational and clinical research focused on the neurodegenerative aspects of autoimmune diseases that affect the nervous system. Specifically, the NINDS aims to understand the role of neurons, glial cells, and the blood-brain barrier in the neuropathology of autoimmune disorders affecting the nervous system and to assist in therapy development targeting these aspects.

National Institute of Nursing Research (NINR) NINR supports rigorous science conducted by scientists from any discipline and is interested in the topics above, with a focus on research addressing the holistic needs of individuals, families, and communities affected by autoimmune diseases and effective clinical and organizational solutions that optimize their health and care delivery.

Research topics of interest include, but are not limited to: Multilevel interventions (e.g., community, family, and organization levels) to enhance early diagnosis, slow progression, and improve treatment outcomes among populations adversely impacted by autoimmune disease based on social, economic, or geographic characteristics Development and adaptation of diagnostics, biomarkers, and emerging technologies that improve early diagnosis, treatment, and outcomes among populations adversely impacted by autoimmune disease based on social, economic, or geographic characteristics CDR Nadra Tyus, DrPH, MPH National Library of Medicine (NLM) The National Library of Medicine (NLM) is interested in advancing research that leverages multi-modal, data-driven approaches to accelerate understanding of autoimmune disease risk and progression.

NLM seeks projects that integrate diverse data types—including genetic, exposome, immunologic, clinical, behavioral, imaging, and sensor data—to reveal shared mechanisms underlying pre-clinical autoimmunity, disease inception, and flares.

NLM is particularly interested in studies that harness computational tools and collaborative networks, advance diagnostics, biomarkers, predictive models, and emerging technologies, and develop novel models such as new approach methodologies (NAMs).

NLM also encourages efforts to create interoperable data standards, platforms, and analytic frameworks that enable integration and reuse of multi-modal datasets, fostering reproducibility, scalability, and translational impact across autoimmune disease research. For technical issues E-mail OER Webmaster