One morning, cardiologist Monica Aggarwal, MD, found herself on the floor and unable to move. Her joints had grown so inflamed and stiff that she felt nearly paralyzed. Soon after, a doctor diagnosed her with rheumatoid arthritis and said that she needed to get used to the idea of living in pain. On this episode of The Exam Room™ podcast, “The Weight Loss Champion” Chuck Carroll is joined by Dr. Aggarwal who shares her inspirational journey back to health with the help of a plant-based diet.
Autoimmune diseases are conditions where your immune system mistakenly attacks your body. We know from previous research that the composition of the gut microbiome, the billions of microorganisms living in the human digestive system, is linked to the development of autoimmune diseases. However, the contribution of the gut virome – the viruses living in our gastrointestinal tract – in autoimmune diseases is unknown.
In a study recently published in Annals of the Rheumatic Diseases, researchers from Osaka University Graduate School of Medicine have shown that in people suffering from autoimmune diseases, the composition of the gut virome is compromised.
Autoimmune diseases cause significant chronic morbidity and disability worldwide. They include rheumatoid arthritis, which is most common in older adults, and systemic lupus erythematosus, which is relatively prevalent among young women. The human gastrointestinal tract contains diverse populations of bacteria, fungi, viruses, and other microorganisms collectively called the gut microbiome. It is now widely recognised that the gut microbiome markedly influences our health via the immune and metabolic systems.
Although they make up a large proportion of the gut microbiome, the contribution of viruses to the effects on health has been far less studied than that of the bacterial component of the gut microbiome because of the technical difficulty of studying these tiny entities. The most predominant component of the gut virome are bacteriophages, viruses that infect bacteria and can alter their physiological function. The Osaka team aimed to investigate the role of bacteriophages in the gut microbiome of individuals with autoimmune diseases in order to reveal a potential link.
The researchers analysed the gut virome of 476 Japanese individuals, including 111 patients with rheumatoid arthritis, 47 patients with systemic lupus erythematosus, 29 patients with multiple sclerosis, and 289 healthy control volunteers. They constructed a new analytic pipeline to recover viral sequences from whole-metagenome shotgun sequencing data. This enabled them to quantify the abundance of the viruses that reside within the gut environment, providing an invaluable tool to study viruses, which are otherwise difficult or impossible to analyse.
“Our case–control comparison of viral abundance revealed that crAss-like phages, which are one of the main components of a healthy gut virome, were significantly less abundant in the gut of the patients with autoimmune disease, particularly in patients with rheumatoid arthritis and systemic lupus erythematosus,” says Yoshihiko Tomofuji, lead author of the study.
The investigators went on to use CRISPR-based analysis to study possible bacterial targets of crAss-like phages. They observed that the virus called Podoviridae, which has a symbiotic relationship to the bacteria Faecalibacterium, significantly decreased in the gut of the patients with systemic lupus erythematosus. “These analyses have revealed a previously missing part of the autoimmunity-associated gut microbiome and presented new candidates that contribute to the development of autoimmune diseases,” explains Yukinori Okada, senior author of the study.
From a therapeutic perspective, understanding the composition of the gut virome of individuals with autoimmune diseases is important because it allows the development of targeted therapies to keep the microbiome, and potentially the disease, under control.
Rheumatoid Arthritis is an auto-immune inflammatory arthritis that if it is not treated it can slowly destroy the joints of the shoulders, elbows, wrists, fingers, knees, ankles and feet. Medication and anti-inflammatory diet are the most important methods to stop the disease and avoid joint destruction. Exercises are used in conjunction with medications to preserve the function of the joints, to avoid disability, to improve morning stiffness and to reduce pain.
Black and Hispanic patients often had higher disease activity and lower self-reported functional status when compared to white patients.
Rheumatoid arthritis (RA) is the most common type of autoimmune arthritis. It is caused when the immune system (the body’s defense system) is not working properly. RA causes pain and swelling in the wrist and small joints of the hand and feet. RA can sometimes cause various systemic effects, such as severe fatigue or organ damage to the heart, lungs or eyes.
Research has shown that there are differences in disease activity and clinical outcomes for people with RA across different racial and ethnic groups in the United States. The authors conducted this new study to learn more about these disparities and how they may have changed over time.
“Disparities exist across the healthcare system, and these inequities impact both patient experience as well as patient clinical outcomes,” says Jacqueline O’Brien, PhD, a clinical epidemiologist at CorEvitas, LLC, and the study’s co-author. “However, this has not been studied as extensively in RA as in other disease areas, so there is still a need to understand the magnitude of health disparities in RA. We need to identify where the disparities exist, so that we can better target therapy and improve care, for all patients.”
Researchers used data from the CorEvitas registry of over 56,000 RA patients living in 42 U.S. states. They included patients who had clinic visits between 2013 and 2015 and 2018 and 2020. Patients self-reported their race and ethnicity and were grouped as either Black (non-Hispanic), white (non-Hispanic), Hispanic or Asian. Clinical Disease Activity Index (CDAI) was used at both visits to measure RA disease activity.
There were 9,363 participants, mostly female and in their late 50s, including 8,142 white, 527 Black, 545 Hispanic and 149 Asian. Their RA disease duration ranged from about 10 to 12 years. More than half of patients had a history of serious infections. Up to 41% had a history of hypertension.
The study’s primary outcome was the Clinical Disease Activity Index score. Secondary outcomes were the proportion of patients with low disease activity or remission and HAQ-disability index, a measure of physical function, at each visit. In addition to examining the outcomes cross-sectionally, the researchers evaluated the mean change in disease activity and physical function scores from the first to the second visit, and the probability that patients would achieve low disease activity or remission by the second visit.
Estimated Clinical Disease Activity Index remained significantly higher, meaning greater disease activity, for Hispanic patients compared to white patients at both time points. Disease activity improved over the 7-year study period among all racial and ethnic groups, though Hispanic patients improved less than white patients. There were differences in functional status at both time points, with Black and Hispanic patients having higher scores, meaning worse functional impairment, compared to white patients. The racial and ethnic groups achieved low disease activity and remission at similar rates between the two time periods.
“Our study was designed to evaluate clinical outcomes, and unfortunately does not address issues related to access to care. We saw that all patients demonstrated improvement over time, but even after adjustment for potential confounding variables, such as the study site, prior and current biologic use, insurance status, education, there were still differences between the racial and ethnic groups at the second time point,” O’Brien says. “Many factors contribute to health inequity, including access to care, socioeconomic status, systemic racism, and other social determinants of health. Certainly, more research is needed to understand how these factors interact and result in different clinical outcomes for racial and ethnic groups.”
Patients with rheumatoid arthritis are at increased risk of a surprise heart attack, according to new research presented today at ICNC 12 by Dr Adriana Puente, a cardiologist in the National Medical Centre “20 de Noviembre” ISSSTE in Mexico City, Mexico. Risk was increased even when patients had no symptoms and was independent of traditional cardiovascular risk factors such as smoking and diabetes.
Dr Puente said: “Our study suggests that one quarter of patients with rheumatoid arthritis and no symptoms of heart disease could have a heart attack without prior warning.”
ICNC is organised by the Nuclear Cardiology and Cardiac CT section of the European Association of Cardiovascular Imaging (EACVI), a registered branch of the European Society of Cardiology (ESC), the American Society of Nuclear Cardiology (ASNC), and the European Association of Nuclear Medicine (EANM). ICNC 12 is held 3 to 5 May 2015 in Madrid, Spain.
Dr Puente said: “Rheumatoid arthritis affects 1.6% of the general population and is the first cause of consultation in the rheumatology service. The condition nearly doubles the risk of a heart attack but most patients never knew they had heart disease and were never alerted about their cardiovascular risk.”
The study investigated the presence of ischaemia and infarction secondary to atherosclerotic disease (coronary artery disease) in 91 patients with rheumatoid arthritis and traditional cardiovascular risk factors but no symptoms of heart disease. Inflammatory markers, rheumatoid arthritis disease activity and risk factors were measured in all patients. Existence of ischaemia and infarction were assessed using the nuclear cardiology method Gated Single Photon Emission Computed Tomography (SPECT).
The researchers found that 55% of patients had dyslipidemia (high blood lipids), 32% had hypertension, 14% were smokers and 10% had type 2 diabetes. Nearly one quarter (24%) of patients had abnormal Gated SPECT, indicating ischaemia or infarction. There was no significant correlation between the presence of ischaemia or infarction and rheumatoid arthritis disease activity, inflammatory markers or cardiovascular risk factors.
Dr Puente said: “Our study shows that one quarter of patients with rheumatoid arthritis and no symptoms of heart disease do have coronary heart disease, as evidenced by the presence of myocardial ischaemia or infarction in the Gated SPECT study. This means they are at increased risk of cardiovascular death.”
She added: “The ischaemia and infarction may be explained by the persistence of the systemic inflammation in rheumatoid arthritis which may cause an accelerated atherosclerosis process.1 Our finding of no association between the Gated SPECT results and inflammatory markers could be because all the patients were taking pharmacological treatment.”
Patients in the study were 90% women and 59 years old on average and had a similar frequency of cardiovascular risk factors as the general population. Dr Puente found that the presence of ischaemia or infarction was independent of cardiovascular risk factors.
She said: “The results highlight the importance of conducting diagnostic tests in patients with rheumatoid arthritis to see if they have cardiovascular disease, specifically atherosclerotic coronary artery disease (ischaemia or myocardial infarction) even if they have no symptoms and regardless of whether they have cardiovascular risk factors. This is essential to prevent and reduce cardiovascular mortality.”
Dr Puente concluded: “Patients with rheumatoid arthritis should be told that they have an elevated predisposition to heart disease and need pharmacological treatment to diminish the inflammatory process and atherosclerotic complications. They also need advice on how best to control their rheumatoid arthritis and decrease their cardiovascular risk factors. Patients who take corticosteroids and methotrexate for their rheumatoid arthritis are susceptible to elevated plasma lipid levels and develop hyperhomocysteinemia, respectively, which are both cardiovascular risk factors and require preventative treatment.”