Study finds bacteria in milk linked to rheumatoid arthritis

A team of UCF College of Medicine researchers has discovered a link between rheumatoid arthritis and Mycobacterium avium subspecies paratuberculosis,
known as MAP, a bacteria found in about half the cows in the United
States. The bacteria can be spread to humans through the consumption of
infected milk, beef and produce fertilized by cow manure.

Treatment for Rheumatoid Arthritis and Risk of Alzheimer's Disease: A Nested Case-Control Analysis. - PubMed - NCBI

INTRODUCTION:
It is increasingly becoming accepted that inflammation may play an important role in the pathogenesis of Alzheimer's disease (AD), as several immune-related genes have been associated with AD. Among these is tumor necrosis factor (TNF)-α, a proinflammatory cytokine known to play an important role in autoimmune disorders, including rheumatoid arthritis (RA). Although AD and RA appear to involve similar pathological mechanisms through the production of TNF-α, the relationship between AD and RA remains unknown.

OBJECTIVE:
To determine the relative risk of AD among RA patients and non-RA patients, and whether anti-TNF therapy for RA was associated with a lower risk of AD in RA patients.

METHODS:
We performed a nested case-control study of more than 8.5 million commercially insured adults (aged ≥18 years) in all 50 US states, Puerto Rico, and US Virgin Islands in the Verisk Health claims database. We derived a sub-cohort of subjects with a diagnosis of RA (controls), or RA and AD (cases), matching cases and controls based on age, sex, exposure assessment period, and methotrexate treatment. We also assessed relative risk of AD following exposure to standard RA therapies, including anti-TNF agents (infliximab, adalimumab, etanercept), methotrexate, prednisone, sulfasalazine, and rituximab. Odds ratios were adjusted for comorbidities, including coronary artery disease, diabetes mellitus, and peripheral vascular disease.

RESULTS:
AD was more prevalent (p < 0.0001) among RA patients (0.79 %) than among those without RA (0.11 %). Chronic conditions such as coronary artery disease (odds ratio [OR] 1.48; 95 % confidence interval [CI] 1.04-2.05; p = 0.03), diabetes (OR 1.86; 95 % CI 1.32-2.62; p = 0.0004), and peripheral vascular disease (OR 1.61; 95 % CI 1.06-2.43; p = 0.02) significantly increased the relative risk of AD among RA patients. Exposure to anti-TNF agents as a class, but not other immunosuppressive drugs studied, was associated with lowered risk of AD among RA patients (unadjusted OR 0.44; 95 % CI 0.22-0.87; p = 0.02; adjusted OR 0.45; 95 % CI 0.23-0.90; p = 0.02). Sub-group analysis demonstrated that of the three anti-TNF agents studied, only etanercept (unadjusted OR, 0.33; 95 % CI 0.08-0.94; p = 0.03; adjusted OR 0.30; 95 % CI 0.08-0.89; p = 0.02) was associated with a decreased risk of AD in RA patients.

CONCLUSION:
There is an increased risk of AD in the studied RA population. The relative risk of AD among RA subjects was lowered in those exposed to etanercept. Anti-TNF therapy with etanercept shows promise as a potential treatment for AD."



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Metagenome-wide association study on oral microbiome uncovered markers for rheumatoid arthritis

"Metagenome-wide association studies (MGWAS) have proved to be a powerful approach to study gut microbiome for type 2 diabetes, colorectal cancer, etc. This is the first study on dental and saliva microbiomes. The researchers found that, Haemophilus sp. is depleted in rheumatoid arthritis (RA) patients at all three gut and oral sites and negatively correlates with RA auto-antibodies, while Lactobacillus salivarius is over-represented in RA patients at all three sites, especially in the very active cases.
Functional convergence was also observed—the RA gut and oral microbiomes show abnormalities in the redox environment, iron, sulfur, zinc and arginine transport and metabolism, and possible molecular mimicry to RA-related human antigens."

Genetics can explain why infections trigger onset of different types of rheumatoid arthritis

(Medical Xpress)—A new international study has revealed how genetics
could explain why different environmental exposures can trigger the
onset of different forms of rheumatoid arthritis.

It was already known that a proportion of rheumatoid arthritis
patients test positive for autoantibodies, whilst about 30% remain
sero-negative. In this study, the researchers have better defined the
genetic distinction between these two disease subtypes: sero-positive
and sero-negative rheumatoid arthritis.


They have now established that different genetic variants of a
protein that plays a vital role in how the body's immune system fights
infection are associated with the two forms of rheumatoid arthritis.
This provides clues to the theory that exposure to different infectious
agents, such as bacteria or viruses, trigger the different forms of
rheumatoid arthritis in susceptible individuals. Sero-negative
rheumatoid is less well understood than sero-positive, and patients who
have this type of arthritis can be misdiagnosed, leading to
inappropriate treatment.

Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis

OBJECTIVES:

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which the gut microbiota is altered. Probiotics are microorganisms that can normalize gut microbiota; thus, they may help to alleviate RA symptoms. The objective of the present clinical trial was to assess the effects of probiotic supplementation on disease activity and inflammatory cytokines in patients with RA.

METHODS:

Forty-six patients with RA were assigned into two groups in this randomized, double-blind, placebo-controlled clinical trial. The patients in the probiotic group received a daily capsule that contained a minimum of 10⁸ colony-forming units of Lactobacillus casei 01 for 8 wk. The placebo group took capsules filled with maltodextrin for the same time period. Questionnaires, anthropometric measurements, and fasting blood samples were collected, and the participants were assessed by a rheumatologist at baseline and at the end of the trial.

RESULTS:

Disease activity score was significantly decreased by the intervention, and there was a significant difference between the two groups at the end of the study (P < 0.01). Three of the assessed serum proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-12) significantly decreased in the probiotic group (P < 0.05); however, serum levels of interleukin-1 β were not significantly affected by the probiotic (P = 0.22). The serum level of regulatory cytokine (interleukin-10) was increased by the supplementation (P < 0.05). The proportion of interleukin-10 to interleukin-12 was significantly increased in the probiotic group as well.

CONCLUSIONS:

L. casei 01 supplementation improved the disease activity and inflammatory status of patients with RA. Further studies are warranted to confirm these results, and such confirmation may lead to the introduction of probiotics as adjunctive therapy for this population.

Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis | eLife

Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA - 

Bacteria responsible for gum disease facilitates rheumatoid arthritis | BreakThrough Digest Medical News

 "The scientists found that P. gingivalis produces a unique enzyme, peptidylarginine deiminanse (PAD) which then enhances collagen-induced arthritis (CIA), a form of arthritis similar to RA produced in the lab. PAD changes residues of certain proteins into citrulline, and the body recognizes citullinated proteins as intruders, leading to an immune attack. In RA patients, the subsequent result is chronic inflammation responsible for bone and cartilage destruction within the joints."

Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis : Nature Biotechnology : Nature Publishing Group

Epigenetic mechanisms integrate genetic and environmental causes of disease, but comprehensive genome-wide analyses of epigenetic modifications have not yet demonstrated robust association with common diseases. Using Illumina HumanMethylation450 arrays on 354 anti-citrullinated protein antibody–associated rheumatoid arthritis cases and 337 controls, we identified two clusters within the major histocompatibility complex (MHC) region whose differential methylation potentially mediates genetic risk for rheumatoid arthritis. To reduce confounding factors that have hampered previous epigenome-wide studies, we corrected for cellular heterogeneity by estimating and adjusting for cell-type proportions in our blood-derived DNA samples and used mediation analysis to filter out associations likely to be a consequence of disease. Four CpGs also showed an association between genotype and variance of methylation. The associations for both clusters replicated at least one CpG (P < 0.01), with the rest showing suggestive association, in monocyte cell fractions in an independent cohort of 12 cases and 12 controls. Thus, DNA methylation is a potential mediator of genetic risk.

Epigenetics explains rheumatism? Genes and their regulatory 'tags' conspire to promote rheumatoid arthritis

In one of the first genome-wide studies to hunt for both genes and their regulatory "tags" in patients suffering from a common disease, researchers have found a clear role for the tags in mediating genetic risk for rheumatoid arthritis (RA), an immune disorder that afflicts an estimated 1.5 million American adults. By teasing apart the tagging events that result from RA from those that help cause it, the scientists say they were able to spot tagged DNA sequences that may be important for the development of RA. And they suspect their experimental method can be applied to predict similar risk factors for other common, noninfectious diseases, like type II diabetes and heart ailments.

Autoantibodies could be a warning sign for cardiovascular disease in people with rheumatoid arthritis

ScienceDaily (Nov. 10, 2012) — The presence of autoantibodies in the blood may be connected to a higher risk of the development of cardiovascular disease, not just in individuals with diagnosed autoimmune diseases like rheumatoid arthritis, but in the general population, according to new research findings presented this week at the American College of Rheumatology Annual Meeting in Washington, D.C.

MNT: Novel Potential Treatment For Autoimmune Diseases Inspired By Mother Nature

Reproducing a rare type of B cell in the laboratory and infusing it back into the body may provide an effective treatment for severe autoimmune diseases such asmultiple sclerosis or rheumatoid arthritis, according to researchers at Duke University Medical Center. 
The findings, which were demonstrated in mice, highlight the unique properties of a subset of B cells that normally controls immune responses and limits autoimmunity, in which an organism mistakenly attacks its own healthy tissue. The work appears Oct. 14, 2012, in the journal Nature. 

Related articles

• New point of focus found for the treatment of rheumatoid arthritis and other autoimmune diseases (eurekalert.org)

Rare B cells regulate immune responses, may offer novel treatment for autoimmune diseases

Reproducing a rare type of B cell in the laboratory and infusing it back into the body may provide an effective treatment for severe autoimmune diseases such as multiple sclerosis or rheumatoid arthritis, according to researchers at Duke University Medical Center.

Read more at: http://medicalxpress.com/news/2012-10-rare-cells-immune-responses-treatment.html#jCp

Related articles

• Rheumatoid Arthritis And Other Autoimmune Diseases: New Point Of Focus Found For Treatment (medicalnewstoday.com)

Potential T cell epitopes of Mycobacterium tuberculosis that can instigate molecular mimicry against host: implications in autoimmune pathogenesis.

Molecular mimicry between microbial antigens and host-proteins is one of the etiological enigmas for the occurrence of autoimmune diseases. T cells that recognize cross-reactive epitopes may trigger autoimmune reactions. Intriguingly, autoimmune diseases have been reported to be prevalent in tuberculosis endemic populations. Further, association of Mycobacterium tuberculosis (M. tuberculosis) has been implicated in different autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Although, in silico analyses have identified a number of M. tuberculosis specific vaccine candidates, the analysis on prospective cross-reactive epitopes, that may elicit autoimmune response, has not been yet attempted. Here, we have employed bioinformatics tools to determine T cell epitopes of homologous antigenic regions between M. tuberculosis and human proteomes.

RESULTS:

Employing bioinformatics tools, we have identified potentially cross-reactive T cell epitopes restricted to predominant class I and II alleles of human leukocyte antigens (HLA). These are similar to peptides of mycobacterial proteins and considerable numbers of them are promiscuous. Some of the identified antigens corroborated with established autoimmune diseases linked with mycobacterial infection.

CONCLUSIONS:

The present study reveals many target proteins and their putative T cell epitopes that might have significant application in understanding the molecular basis of possible T cell autoimmune reactions during M. tuberculosis infections.

Raised antibody levels linked to greater long term risk of rheumatoid arthritis

Men and women with raised levels of an antibody known as rheumatoid factor in their blood have up to a 26-fold greater long term risk of developing rheumatoid arthritis, finds a study published in the British Medical Journal today.

Read more at: http://medicalxpress.com/news/2012-09-antibody-linked-greater-term-rheumatoid.html#jCp

New animal model for rheumatoid arthritis

Researchers at Northwestern University Feinberg School of Medicine have created the first animal model that spontaneously develops rheumatoid arthritis (RA) and is predisposed towards atherosclerosis, or hardening of the arteries.

Nanoparticle Exposure Linked To Rheumatoid Arthritis And Other Autoimmune Diseases

Medical News Today: According to a study published in the journal Nanomedicine, researchers have found an association between exposure to nanoparticles and rheumatoid arthritis and the development of other serious autoimmune disease. In addition, the team discovered new cellular targets for developing potential drug therapies to treat autoimmune diseases. The process involves citrullination, the transformation of arginine into citrulline, which can trigger autoimmune diseases.

A cholesterol and actinide dependent shadow biosphere of archaea and viroids in autoimmune diseases.

Endogenous digoxin has been related to the pathogenesis of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis. The possibility of endogenous digoxin synthesis by archaea with a mevalonate pathway and cholesterol catabolism was considered. 10 cases each of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis before starting treatment and 10 age and sex matched healthy controls from general population were chosen for the study. Cholesterol substrate was added to the plasma of the patients and the generation of cytochrome F420, free RNA, free DNA, polycyclic aromatic hydrocarbon, hydrogen peroxide, serotonin, pyruvate, ammonia, glutamate, cytochrome C, hexokinase, ATP synthase, HMG CoA reductase, digoxin and bile acids were studied. The changes with the addition of antibiotics and cerium to the patient's plasma were also studied. The statistical analysis was done by ANOVA. The parameters mentioned above were increased the patient's plasma with addition of cholesterol substrate. The addition of antibiotics to the patient's plasma caused a decrease in all the parameters while addition of cerium increased their levels. An actinide dependent shadow biosphere of archaea and viroids is described in multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis contributing to their pathogenesis.

Sick from your stomach: Bacterial changes may trigger diseases like rheumatoid arthritis

The billions of bugs in our guts have a newfound role: regulating the immune system and related autoimmune diseases such as rheumatoid arthritis, according to researchers at Mayo Clinic and the University of Illinois at Urbana-Champaign.

Regulatory immune cell diversity tempers autoimmunity in rheumatoid arthritis

Untangling the root cause of rheumatoid arthritis has been a difficult task for immunologists, as decades of research has pointed to multiple culprits in our immune system, with contradictory lines of evidence. Now, researchers at The Wistar Institute announce that it takes a diverse array of regulatory T cells (a specialized subset of white blood cells) to prevent the immune system from generating the tissue-specific inflammation that is a hallmark of the disease. Regulatory T cell diversity, the researchers say, provides a cumulative protective effect against rheumatoid arthritis. When that diversity is not present, it allows the immune system to attack joints.