Putting the Pieces Together
Polyautoimmunity in Rheumatoid Arthritis
So far, the scientific research on Multiple Autoimmune Syndrome has highlighted that polyautoimmunity—the existence of two or more autoimmune diseases, that meet study classification criteria, in one person—and Sjogren’s Syndrome have a strong association with each other. But what about other commonly recognized autoimmune diseases? Rheumatoid arthritis is one of the more iconic autoimmune diseases. Because of this, it is well represented in the available research on Multiple Autoimmune Syndrome. Despite being the primary diagnosis of the largest segment, by far, of research participants in studies on Multiple Autoimmune Syndrome, Rheumatoid arthritis is not as strongly associated with polyautoimmunity as other autoimmune diseases. In this article, I’ll highlight one new study, Frequency of Polyautoimmunity in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus, in the context of two other studies that I have already reviewed, to evaluate the connection between Rheumatoid arthritis and polyautoimmunity.
Self-reported polyautoimmunity ranged from 13.8-32.2% in participants with Rheumatoid arthritis. The third study, focusing on a narrower range of lab values, showed zero participants with Rheumatoid arthritis and polyautoimmunity. Multiple autoimmune syndrome was reported by one participant in one study.
It’s important that associations between autoimmune disease and polyautoimmunity exist to greater and lesser extents in different autoimmune diseases. It suggests that polyautoimmunity is not a common component of all autoimmune disease. It suggests that autoimmune diseases, like Rheumatoid arthritis, may be better defined and better characterized than autoimmune diseases like Sjogren’s syndrome and Systemic Lupus Erythematosus. This has practical implications for the trustworthiness of a Rheumatoid arthritis diagnosis and the efficacy of research-backed treatments for Rheumatoid arthritis.
I’ll address the research on Systemic Lupus Erythematosus and polyautoimmunity in a separate post.
Area of Investigation
Multiple Autoimmune Syndrome: when one person meets the study classification criteria for three or more autoimmune diseases.
Study Titles
Frequency of Polyautoimmunity in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus
Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist
New insights into the taxonomy of autoimmune diseases based on polyautoimmunity
Results
Frequency of Polyautoimmunity in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus
109 patients with Rheumatoid Arthritis (RA) were included
of the patients with Rheumatoid Arthritis 15 (or 13.8%) reported polyautoimmunity
8 (53.3%) reported co-occurring Sjogren’s Syndrome
4 (26.7%) reported co-occurring Hashimoto’s thyroiditis
3 (20%) reported co-occurring psoriasis
5 (33.3%) reported a 1st degree family member with polyautoimmunity
One patient with Rheumatoid arthritis reported multiple autoimmune syndrome
Obesity was associated with polyautoimmunity in Rheumatoid arthritis
It’s outside of the scope of this newsletter, but for a thorough critique of obesity, and obesity associations in scientific research, I recommend
Positive anti-RO and anti-LA antibodies indicated polyautoimmunity
No patients with Rheumatoid arthritis and polyautoimmunity were positive for anti-RNP or anti-Sm antibodies
Among the 15 of 109 patients with polyautoimmunity
7 of 15 (46.7%) were diagnosed with polyautoimmunity at the same time
5 of 15 (33.3%) presented Rheumatoid arthritis as the first autoimmune disease
3 of 15 (20%) were diagnosed with another autoimmune disease first
Mean time between initial Rheumatoid arthritis diagnosis and additional autoimmune disease diagnosis was 5.0 years
Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist
Of 304 participants with Rheumatoid arthritis
32.2% had polyautoimmunity
21.1% had co-occurring Autoimmune thyroid disease
11.8% had co-occurring Sjogren’s syndrome
New insights into the taxonomy of autoimmune diseases based on polyautoimmunity
Out of 146 study participants with a diagnosis of Rheumatoid arthritis, none of them showed higher-than-control levels of the 111 IgG immune proteins that were studied. In the context of the particular IgG immune protein metric that this study used to explore polyautoimmunity, participants with Rheumatoid arthritis did not show signs of polyautoimmunity, when compared to participants with a diagnosis of Systemic Lupus Erythematosus, Sjogren’s syndrome, Autoimmune thyroid disease, and Systemic sclerosis, despite making up the largest group of participants studied.
Risk Factors for Polyautoimmunity
Risk factors for polyautoimmunity in participants with Rheumatoid arthritis included a 1st degree family member with polyautoimmunity, obesity, and positive anti-RO and anti-LA antibodies.
NOT Associated with Risk of Polyautoimmunity
Anti-RNP or anti-Sm antibodies were not associated with polyautoimmunity and Rheumatoid arthritis.
Why It Matters
More research is needed, but these studies point to a fundamental difference between the association of polyautoimmunity and Rheumatoid arthritis, and the association between polyautoimmunity and other autoimmune diseases, like Sjogren’s syndrome. A lower association of polyautoimmunity with Rheumatoid arthritis could mean that Rheumatoid arthritis is better described, and more accurately diagnosed, than other autoimmune diseases. This diagnostic clarity makes it easier to study disease process, and most importantly, easier to study treatments. Because of this, Rheumatoid arthritis has the potential to serve as a standard for diagnostic clarity.
Polyautoimmunity has been shown to develop over time, but the development of polyautoimmunity over time does not appear to be as prevalent in Rheumatoid arthritis. Why not? This potential difference between Rheumatoid arthritis, and other autoimmune diseases that are more associated with polyautoimmunity, provides the critical opportunity to compare disease processes and research differences.
Study Type
Frequency of Polyautoimmunity in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus is self-identified as an observational cross-sectional study on polyautoimmunity in patients with Rheumatoid Arthritis (109 patients), Systemic Lupus Erythematosus (105 patients), and 88 controls without autoimmune rheumatic disease, all recruited from a rheumatology clinic. A cross-sectional study is
A type of research study in which a group of people is observed, or certain information is collected, at a single point in time or over a short period of time. For example, a survey may be done to collect information about the total number of people in a group who have or had a certain disease (such as cancer) or risk factor (such as smoking or obesity). In this example, the survey may be able to provide some information about whether there is an association between the smoking (risk factor) and the cancer (disease) but does not prove that they are linked. Results from a cross-sectional study may be used to plan other research studies. A cross-sectional study is a type of observational (epidemiologic) study.
An observational retrospective study is defined this way
A study that compares two groups of people: those with the disease or condition under study (cases) and a very similar group of people who do not have the disease or condition (controls). Researchers study the medical and lifestyle histories of the people in each group to learn what factors may be associated with the disease or condition.
This study seems to teeter between these two definitions, since it relies on the completion of a survey, but also includes a control group without Rheumatoid arthritis or Systemic lupus erythematosus. I would characterize this study as an observational retrospective study, but I’ll take the author’s characterization of the study being an observational cross-sectional study at face value.
In case your interest extends this far, the study types of the other two studies included in this post are described in their original reviews, found here and here.
References
Ordoñez-Cañizares MC, Mena-Vázquez N, Redondo-Rodriguez R, Manrique-Arija S, Jimenez-Núñez FG, Ureña-Garnica I, Fernández-Nebro A. Frequency of Polyautoimmunity in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus. J Clin Rheumatol. 2022 Jan 1;28(1):e38-e43. doi: 10.1097/RHU.0000000000001574. PMID: 32956154.
Rojas-Villarraga A, Amaya-Amaya J, Rodriguez-Rodriguez A, Mantilla RD, Anaya JM. Introducing polyautoimmunity: secondary autoimmune diseases no longer exist. Autoimmune Dis. 2012;2012:254319. doi: 10.1155/2012/254319. Epub 2012 Feb 20. PMID: 22454759; PMCID: PMC3290803.
Rojas M, Ramírez-Santana C, Acosta-Ampudia Y, Monsalve DM, Rodriguez-Jimenez M, Zapata E, Naranjo-Pulido A, Suárez-Avellaneda A, Ríos-Serna LJ, Prieto C, Zambrano-Romero W, Valero MA, Rodríguez Y, Mantilla RD, Zhu C, Li QZ, Toro-Gutiérrez CE, Tobón GJ, Anaya JM. New insights into the taxonomy of autoimmune diseases based on polyautoimmunity. J Autoimmun. 2022 Jan;126:102780. doi: 10.1016/j.jaut.2021.102780. Epub 2021 Dec 16. PMID: 34923432.