Already feel like a medical guinea pig? Join the official count:
Polyautoimmunity, Multiple Autoimmune Syndrome & Making the Case for Registries
The diagnosis and clinical significance of polyautoimmunity is the second in a series of 21 results that I’m reviewing to better understand and characterize Multiple Autoimmune Syndrome, a condition where one person has three or more autoimmune diseases that fit standard diagnostic criteria. Unfortunately, it turned out to be a review article, summarizing the knowledge about polyautoimmunity and multiple autoimmune syndrome to date. It was published in 2014 by Autoimmunity Reviews. It was written by one of the authors of the 2011 study Introducing polyautoimmunity…, which is an observational cross-sectional study I have already reviewed here.
Although I have access to more than an abstract of The diagnosis and clinical significance of polyautoimmunity, I frustratingly don’t have access to the full text of the article. For these two reasons: 1. not a scientific study, but a summary of knowledge to date and 2. full text unavailable—I won’t be doing a review. Still, the introduction to this article included important characterizations of Autoimmune disease (AD) that I can’t resist exploring.
From the introduction:
Several subphenotypes are shared by ADs including signs and symptoms such as arthralgia, arthritis, alopecia, fatigue, photosensitivity, Raynaud's phenomenon as are non-specific autoantibodies (e.g., antinuclear antibodies, rheumatoid factor, anti-Ro antibodies) and high levels of cytokines which raises taxonomic concerns and explain why classification criteria may lack of accuracy. ADs have a heterogeneous spectrum; the disease course differs from patient to patient and through different phases within the same patient. Depending on the duration and activity of the disease, these subphenotypes might change. Mathematical approaches for precisely defining subphenotypes based on accurate clinical and immunological databases combined with strengthening molecular genetic analyses and immunological pathways (e.g., type I interferon activation, reduced B and T cell regulatory function) have significant promise for a better understanding of ADs.
(Anaya, 2014)
I like this quote because it succinctly sums up the problems with classifying, and thus diagnosing, autoimmune disorders. It also quickly outlines the path forward.
Problems
Phenotypes (signs of disease such as observable clinical presentations and test results) are shared among autoimmune diseases
classification criteria lacks accuracy
Signs and symptoms of autoimmune diseases differ from patient to patient, and within a single patient over time
Path forward
accurate clinical and immunological databases
molecular genetic analyses
identifying specific, dysfunctional immune system processes causing disease signs and symptoms
Is the path forward achievable? Has progress been made since this article was published in 2014? In a subsequent 2015 article in Autoimmunity Reviews, Johar, et al (including the author above, Anaya) propose the use of Whole Exome Sequencing in patients with Multiple Autoimmune Syndrome. The authors argue that this is an available and cost-effective technique to evaluate underlying genetic differences in people with Multiple Autoimmune Syndrome. The technique would need to be tested and validated in a research setting before being used in a clinical setting, but the technology exists now and has been used to detect other rare genetic disorders. Connecting researchers, who have the interest and funding to pursue this line of inquiry, to people with Multiple Autoimmune Syndrome, is the next step. That brings us back to the need for an accurate clinical and immunological database, which is foundational to the other two goals—genetic analysis and immune process identification. Does it exist?
I first went to the Autoimmune Association website to search for an “accurate clinical and immunological database.” I learned that the Autoimmune Association has an international autoimmune disease patient registry “created to look for patterns in treatments, side effect management and diagnostics that may lead to improved treatment options and outcomes for patients” (2022, Autoimmune Association). Although it’s far from an accurate clinical and immunological database—where patient histories, signs, symptoms, test results, procedures, diagnoses and outcomes would be organized and accessible to researchers, the Autoimmune Association’s patient registry could be the foundation for building a comprehensive database.
You may have concerns about signing up for a patient registry designed to allow researchers to contact you about participation in clinical trials and observational studies, and that’s completely understandable. Please consider this, participation in any given study is optional based on the risks of the individual study (informed consent is mandated by law in the United States). The non-invasive survey form you fill out to register is, itself, a study in diagnosis type, delays in diagnosis, and demographic information, that can provide researchers with a wealth of information simply by filling out a form. One drawback is that you need a doctor-confirmed autoimmune diagnosis to participate, and it has to be a diagnosis that’s included on the Autoimmune Association’s diagnosis list. We have seen from the search for a comprehensive diagnostic list, that the Autoimmune Association’s list differs significantly from another authoritative list, and may not include some autoimmune diagnoses.
I was able to find one other Autoimmune Registry that was established in 2016
to reduce the time of diagnosis, support research, compute prevalence statistics, and establish autoimmune disease as a major class of disease so that it receives the awareness of the public, the attention of healthcare providers, and the appropriate funding needed to improve upon existing treatment protocols and disease management strategies.”
It was on the Autoimmune Registry website that I found this especially persuasive pitch:
Suppose we have a drug that could cure Lupus…
Today it would take 2 years just to find patients to test it.
Imagine we could find those patients in 2 days.
40% of clinical trials fail because researchers cannot find enough patients to participate. Without patients willing to participate in clinical research, we cannot find new drugs, new diagnostic tests, or new treatments. Your participation counts!
The Autoimmune Registry helps recruit patients like you for clinical research and clinical trials. When a trial begins, we contact you to see if you can participate. You won’t be able to participate in every study, but every study you participate in gets us a step closer to the tests, treatments and cures for autoimmune disease.
(2022, Autoimmune Registry)
I’ll leave it to you to evaluate how trustworthy and authoritative you find these two registries. I really enjoyed reading the profiles of the Autoimmune Registry staff and board of directors—all of them impacted in some way by autoimmune disease. And of course, it’s not an either/or proposition. If you’re so moved, you could join both. These are opportunities to be counted, to be seen, and if you’re willing, to advance the available scientific evidence on autoimmune diseases.
Okay, but how does signing up for a registry get us to an accurate clinical and immunological database? Let’s consider the United States alone. It would require coordination across hundreds of health care systems. Sounds complicated. Except that the United States already does this for cancer. The National Program of Cancer Registries collects standardized information under the umbrella of the CDC. Each hospital/clinic system has a position known as a cancer registrar, who collects institution-wide patient data for the national registry and follows up with providers if required information is missing. There are also private contractors that do this for healthcare institutions.
Why would hospital and clinic systems participate in a national registry that costs them time and money? Is it because they’re committed to advancements in patient care? It’s possible. However, it’s more probable that hospital and clinic system reimbursements from the Centers for Medicaid and Medicare Services are tied to their participation. There’s either a financial carrot or a stick, beyond the altruistic best interests of the patient, at work here. The same action, on a federal level, needs to happen for autoimmune disorders. The Autoimmune Association Registry and the Autoimmune Registry are the building blocks that might get us to a National Program of Autoimmune Registries. This is the path forward for quantifying the impact that autoimmune disorders have on the U.S. population, so the demand for research dollars, attention and federal incentives for healthcare systems to participate in research are obvious and overwhelming.
References
Anaya JM. The diagnosis and clinical significance of polyautoimmunity. Autoimmun Rev. 2014 Apr-May;13(4-5):423-6. doi: 10.1016/j.autrev.2014.01.049. Epub 2014 Jan 11. PMID: 24424171.
Johar AS, Anaya JM, Andrews D, Patel HR, Field M, Goodnow C, Arcos-Burgos M. Candidate gene discovery in autoimmunity by using extreme phenotypes, next generation sequencing and whole exome capture. Autoimmun Rev. 2015 Mar;14(3):204-9. doi: 10.1016/j.autrev.2014.10.021. Epub 2014 Nov 1. PMID: 25447288.
Research Participation. Autoimmune Registry. (2022). Retrieved November 27, 2022, from https://www.autoimmuneregistry.org/research-participation