To the Office of Autoimmune Disease Research: Happy Belated Birthday!
This week, I’m taking a break from researching and populating the Diagnosis Descriptions for individual, named, autoimmune diseases to write about an exciting recent development in autoimmune disease research. The polyautoimmunity expert Dr. Juan Manuel Anaya has made the case for “accurate clinical and immunological databases” for autoimmune disease. Polyautoimmunity is when one person meets the study classification criteria for two or more autoimmune diseases. Polyautoimmunity encompasses and replaces the term Multiple autoimmune syndrome (when one person meets the study classification criteria for three or more autoimmune diseases). Last December, I argued for a national autoimmune disease registry akin to the U.S. National Cancer Registries. I thought we were a long way off from accurate clinical and immunological databases, and we still are. But, there’s a small, bright light at the end of this autoimmune ignorance tunnel. It takes the form of Congressional law mandating, and allocating funds for, autoimmune disease research: Public Law 117–328.
About Public Law 117–328
Scratch what I said above about how this law mandates, and allocates funds for, autoimmune disease research. That was an inaccurate characterization based on this quote from a press release from the National Institutes of Health, Office of Research on Women’s Health (ORWH)
The creation of this office {Office of Autoimmune Disease Research} within ORWH was mandated by Congress in the Consolidated Appropriations Act, 2023 (Public Law 117–328).
You can see how this press release makes it sound as if the law specifically allocated funds for autoimmune disease research. It did not. When I read the applicable part of the law, I found that it actually states this:
Provided further, That the funds made available under this heading for the Office of Research on Women's Health shall also be available for making grants to serve and promote the interests of women in research, and the Director of such Office may, in making such grants, use the authorities available to NIH Institutes and Centers.
You can see from the actual wording of the law that the Office of Research on Women’s Health was granted broad authority, and they announced on April 12th that they will use that broad authority to create the Office of Autoimmune Disease Research. Truly cool, but not as reliable as a legal mandate.
Why Fund Autoimmune Disease Research Instead of Something Else?
To me, the reasons are obvious, but the government office spending taxpayer money needs a basis for their decision. Enter this report, titled _Enhancing NIH Research on Autoimmune Disease (2022)_ published by The National Academies of Sciences, Engineering, and Medicine. I just learned that Congress established the National Academy of Science way back in 1863 to advise the nation on science and technology. It was established by law as a private, nongovernmental institution with members who are elected by their peers for their outstanding contributions to science and technology. I’m so curious to explore how an organization established by the U.S. government can be private and nongovernmental—and also how peer-elected membership likely tends toward institutional blind spots and entrenched inequity. Trigger underlying criticism that establishing a national autoimmune disease research office took. this. long. Argh, critical scope creep is real…and I’ll force myself back on track now. At a whopping 549 pages, I don’t have time to read it right now—after all, Palindromic rheumatism beckons—but the introduction outlines how this report came about, and hints at what it contains:
Congressional legislation has often assisted in focusing National Institutes of Health (NIH) efforts to meet urgent demands related to the health and welfare of U.S. citizens. In 2019 Congress called for NIH to contract with the National Academies of Sciences, Engineering, and Medicine to identify and review NIH’s research efforts in the broad area of autoimmune diseases with a particular emphasis on the risk factors, diagnostic tools, barriers to diagnosis, treatments, and prospects for cure.
So, what are we really talking about here in terms of how much money and for how long? That’s unclear. From Public Law 117–328, it appears there’s a lot of flexibility in how the National Institutes of Health director allocates a budget of $2,642,914,000. Despite the lack of clarity surrounding the budget, what is clear from the Office of Research on Women’s Health press release is that there are three calls for research proposals.
The Three Calls
EXposome in Autoimmune Disease Collaborating Teams PLANning Awards (EXACT-PLAN) (Clinical Trials Not Allowed)
Understanding Chronic Conditions Understudied Among Women (R21 Clinical Trial Optional)
Understanding Chronic Conditions Understudied Among Women (R01 Clinical Trial Optional)
1. Exposome in Autoimmune Disease
Exposome is a new term for me. It’s “defined as the measure of all the exposures of an individual lifetime and how those exposures relate to an individual’s health, on disease susceptibility onset and severity.” This call for research proposals focuses on the fundamentals of establishing a
national, interdisciplinary, collaborative, team science research network that will advance the study of the exposome in autoimmune diseases…The future…initiative is envisioned as a multisite, collaborative network that will adopt a team science approach to produce a systems level understanding of the role of the exposome in AID {autoimmune disease}.
One focus of the requested research is “sensing wearables” that have already been validated for monitoring toxic exposure (air pollutants and chemicals), and which have the potential to be validated in other areas, such as monitoring sleep, stress, diet, and the microbiome. A sensing wearable is a monitoring device that a study participant is able to wear while going about their day.
The call for proposals emphasizes that “collaborations with successful programs such as the All of Us, Accelerated Medicine Partnership® Autoimmune and Immune Mediated Diseases, and Environmental Influences in Child Health Outcomes (ECHO) programs will be encouraged.” All of Us is available to participants in many parts of the U.S., and I review the sign up process here. They’re also encouraging research proposals that conduct “a landscape analysis of relevant existing resources, databases, registries, repositories, programs, and consortia.”
The call for proposals wants research on the resources needed (examples: study populations, biospecimens, data, devices), and/or the resources that are already available, to study the impact of the exposome on
autoimmune disease in early life?
distinct and interacting biological and biopsychosocial factors contributing to observed and/or differences in AID, including the effect of puberty, menopause, and pregnancy?
pregnancy and postpartum outcomes in patients with AID?
How do non-chemical stressors such as psychosocial factors and social determinants of health, including gender, interact with the exposome to influence disease prevalence and severity among different populations?
How do key exposures across different domains (i.e., biological, behavioral, physical/built, sociocultural, healthcare system) and levels (i.e., individual, family, community, society) that comprise the environmental exposome singly or cumulatively impact AID across the lifetime?”
The scope of the above questions are sweeping. It would be hard to overstate how “big picture” they are. One of the most promising aspects of this particular call is that “Applicants are encouraged to include two or more AID.” Yes! Autoimmune diseases share a common origin. The current segregation of autoimmune disease into named diagnoses by body system, and medical specialty, has fractured autoimmunity into a difficult-to-study cacophony. It warms my heart to see the encouragement to include more than one named autoimmune disease in individual research proposals.
2, 3. Understanding Chronic Conditions Understudied Among Women (R21 Clinical Trial Optional) and Understanding Chronic Conditions Understudied Among Women (R01 Clinical Trial Optional)
The other two calls for proposals are nearly identical, except for their optional Clinical Trial types, and a focus of the third on cancer research. These two calls for proposals are part of broader research goals that now include an autoimmune focus to:
Discover basic biological differences between females and males.
Investigate the influence of sex and gender on disease prevention, presentation, management, and outcomes.
Identify the immediate, mid-, and long-term effects of exposures on health and disease outcomes.
Promote research that explores the influence of sex and gender on the connection between the mind and body, and its impact on health and disease.
Expand research on female-specific conditions and diseases, including reproductive stages, and maternal and gynecologic health.
Why It Matters
The creation of this federal office for funding autoimmune disease research is a critical step toward national clinical and immunological databases, and more accurate and comprehensive research. I’m excited by the focus on underlying environmental factors, the development of foundational research networks, and emphasizing multiple autoimmune diseases. This is promising in the way that a newborn baby is promising—vulnerable, uncoordinated, with blurry vision—but present, breathing independently, and very much alive. Happy belated birthday, Office of Autoimmune Disease Research.
Random List of Existing Toxic Exposure Resources
In the process of reading through the call for proposals, I noted the following new-to-me resources for information on toxins, and I had to include them for reference for Diagnosis Descriptions—and I thought readers might find them useful, too.
Human Health Exposure Analysis Resource at https://hhearprogram.org/, and its associated data center at https://hheardatacenter.mssm.edu/, and the ontology they have established at https://bioportal.bioontology.org/ontologies/HHEAR
the Comparative Toxicogenomics Database at https://ctdbase.org/
the EPA CompTox Dashboard at https://www.epa.gov/chemical-research/comptox-chemicals-dashboard,