Yoga maintains Th17/Treg cell homeostasis and reduces the rate of T cell aging in rheumatoid arthritis: a randomized controlled trial.

The pathogenesis of rheumatoid arthritis (RA) is characterized by a Th17/Treg cell imbalance. A pro-inflammatory cytokine milieu that promotes the continued proliferation of Th17 cells is related to the development of autoinflammation. In RA, T cells have several hallmarks of cellular aging, and they accumulate DNA damage, predisposing to the occurrence of mutations and epigenetic alterations. Since the onset, progression, and treatment response are influenced by a variety of external stressors and environmental factors, this study aimed to evaluate the impact of 8-week yoga practice on disease severity, T cell subsets, markers of T cell ageing and inflammation, epigenetic alterations and gene expression patterns in active RA patients on standard disease-modifying anti-rheumatic drugs (DMARDs). A total of 64 participants with active RA were randomized into 2 groups, yoga group (n = 32) or non-yoga group (n = 32); that were assessed for disease severity, at baseline and after 8 week duration, for Disease Activity Score (DAS28-ESR), T cell subsets [Th17 (CD3+ CD4+ IL17+ RORγt+) cells and Treg (CD3+ CD4+ CD25+ CD127-Foxp3+) cells], markers of T cell aging [aged Th17 cells (CD3+ CD4+ IL17+ RORγt+ CD28-) and aged Treg cells (CD3+ CD4+ CD25+ CD127-Foxp3+ CD28-)], pro-inflammatory markers [IL-6, and IL-17], anti-inflammatory markers [TGF-ß, and IL-10], epigenetic alterations [5-methyl cytosine, 5-hydroxymethyl cytosine, and HDAC1] and gene expression patterns [RORγt, FoxP3, IL-17, IL-6, TGF-ß, CXCL2, CXCR2, and JUN]. In yoga group, there was a significant improvement in DAS28-ESR scores at the end of 8-weeks of yoga program. The Th17 cells and aged T cell subsets showed a significant decline whereas Treg cell population showed a significant elevation in yoga group. There were significant improvements observed in epigenetic markers as well as inflammatory markers post 8-weeks of yoga practice. The yoga group showed downregulation of RORγt, IL-17, IL-6, CXCL2, CXCR2, and upregulation of FoxP3 and TGF-ß transcripts. Yoga enables the maintenance of immune-homeostasis as evident by increased Treg cell population and reduced Th17 cell population. Yoga reduces the rate of immunological aging in T cells, as seen by the reduction in population of aged Th17 cells and aged Treg cells. Yoga positively modifies transcriptome and epigenome by normalization of various inflammatory markers, gene expression patterns and epigenetic alterations. Taken together, yoga reduces RA severity, and aids in immune-modulation and hence can be beneficial as an adjunct therapy.

HLA-G 3'UTR polymorphisms & response to a yoga-based lifestyle intervention in rheumatoid arthritis: A randomized controlled trial.

Background & objectives: Human leucocyte antigen (HLA)-G plays a vital role in immunomodulation in rheumatoid arthritis (RA). The mounting evidence suggests a link between HLA-G gene polymorphisms, disease susceptibility and methotrexate treatment response. Various environmental factors influence the onset and progression of RA and its treatment outcomes. The aim is to identify the treatment response of HLA-G 3' untranslated region polymorphisms to yoga-based lifestyle intervention (YBLI). Methods: In this eight-week single-blinded randomized controlled trial (CTRI/2017/05/008589), patients with RA (n=140) were randomized into two groups namely, yoga group or non-yoga group. Baseline genomic DNA was isolated using salting-out method. PCR-based methods were used for genotyping. The levels of soluble (s) HLA-G and disease activity were assessed by ELISA and disease activity score-28-erythrocyte sedimentation rate (DAS28-ESR), respectively, at baseline (day 0) and after eight weeks of intervention. Results: Low-producing sHLA-G genotypes, i.e. +3142GG and 14 bp ins/ins, showed a significant increase in sHLA-G levels after YBLI. The association analysis between HLA-G polymorphisms and treatment for RA showed no considerable differential treatment remission in either of the groups (P>0.05). The percentages of improvement were higher in the yoga group as compared to the non-yoga group in both the HLA-G +3142G>C and 14 bp ins/del polymorphisms irrespective of their respective genotypes. No significant association was found between sHLA-G levels and disease activity with respect to genotypes. Interpretation & conclusions: Yoga intervention results in improvement and reduced severity of RA in patients irrespective of the HLA-G 14 bp ins/del or +3142G>C polymorphisms. YBLI may be used as an adjunct therapy in RA independent of the genotypes.

Potential Role of Yoga Intervention in the Management of Chronic Non-malignant Pain.

Pain is an unpleasant and upsetting experience. Persistent pain has an impact on an individual's quality of life which causes stress and mood disorders. There are currently no pain-relieving techniques available that can eliminate pain and offer relief without causing any adverse effects. These factors draw attention to traditional treatments like yoga and meditation, which can reduce biological stress and hence increase immunity, as well as alleviate the psychological and emotional suffering produced by pain. Yoga reduces the stress response and the pain cascade via the downregulation of the hypothalamus-pituitary-adrenal (HPA) axis and vagal stimulation. Yoga is a cost-effective growing health practice that, unlike pharmaceuticals, has no side effects and can help patients stay in remission for longer periods of time with fewer relapses. Yoga not only reduces stress and depression severity but also improves functional status and reduces pain perception. This article highlights the impact of yoga on pain management and on a malfunctioning immune system, which leads to improved health, pain reduction, disease management, and improvement in overall quality of life.

Yoga in major depressive disorder: molecular mechanisms and clinical utility.

Major depressive disorder (MDD) is a mind-body disorder. Cellular aging has been implicated in the pathogenesis of MDD with the altered mind-body communication markers like stress response, immune response, nutrition sensing, and a range of other regulatory feedback systems. In this age of super specializations, one specific target and interventions (preferably a drug) on it are being rigorously sought by the health care community and industry, but have failed in it in the last fifty years in spite of advances in technology. Since, depression is a complex disorder associated with increased incidence of other complex disorders, it must be treated by an integrated holistic approach that can address the complexity of MDD. Interventions targeting accelerated biological aging to increase cellular health in whole body have potential to manage complex conditions like MDD and its overlapping symptoms and comorbidities. Yoga has the potential to be the nexus between, clinical management of MDD and other lifestyle diseases.

Yoga improves mitochondrial health and reduces severity of autoimmune inflammatory arthritis: A randomized controlled trial.

BACKGROUND: Oxidative stress (OS) and mitochondrial alterations have been implicated in the pathogenesis of rheumatoid arthritis (RA). Various environmental triggers like air pollutants, smoking, unhealthy social habits and sedentary lifestyle induce OS, which may compromise mitochondrial integrity. This trial was designed to explore the effect of 8-weeks yoga practice on mitochondrial health and disease severity in an active RA group compared with a usual-care control group. METHODS: A total of 70 subjects were randomized into two groups: yoga group and non-yoga group. Mitochondrial health was assessed by calculation of mitochondrial DNA copy number (mtDNA-CN), OS markers, mitochondrial activity, mitochondrial membrane potential (ΔΨm), circadian rhythm markers and transcripts associated with mitochondrial integrity: AMPK, TIMP-1, KLOTHO, SIRT-1, and TFAM. Parameters of disease activity and disability quotient were also assessed by disease activity score - erythrocyte sedimentation rate (DAS28-ESR) and health assessment questionnaire-disability index (HAQ-DI), respectively. RESULTS: In yoga group, there was a significant upregulation of mtDNA-CN, mitochondrial activity markers, ΔΨm, and transcripts that maintain mitochondrial integrity after 8-weeks of yoga. There was optimization of OS markers, and circadian rhythm markers post 8-weeks practice of yoga. Yoga group participants showed significant improvements in DAS28-ESR (p < 0.05) and HAQ-DI (p < 0.05) over the non-yoga group. CONCLUSION: Adoption of yoga by RA patients holds the key to enhance mitochondrial health, improve circadian rhythm markers, OS marker regulation, upregulation of transcripts that maintain mitochondrial integrity, reduce disease activity and its associated consequences on health outcome and hence can be beneficial as an adjunct therapy.

Yoga and its impact on chronic inflammatory autoimmune arthritis.

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases, which adversely affects the quality of life. RA is a disease of unknown etiology, however, both genetic and environmental factors appear to contribute to the susceptibility to this disease. The severity and progression of the disease are attributable to the release of a host of inflammatory cytokines, cytotoxic and immune regulatory factors. The treatments of RA are primarily limited to symptomatic alleviation of pain or other symptoms or to the use of cytotoxic drug treatment in severe forms of the disease which is commonly associated with significant side effects. Despite lack of a cure, the disease may be controlled by mind-body interventions. Holistic treatments such as Yoga significantly improve and reduce the psycho-somatic symptoms, pain perception, disability quotient, joint flexibility, range of motion, posture, muscle strength, coordination, and disease activity. Here, we discuss the features of RA and address how Yoga can be used as a therapeutic regimen to improve the quality of life of patients with RA.

Effect of an 8-Week Yoga-Based Lifestyle Intervention on Psycho-Neuro-Immune Axis, Disease Activity, and Perceived Quality of Life in Rheumatoid Arthritis Patients: A Randomized Controlled Trial.

Various external stressors and environmental challenges lead to the provocation of the immune system in autoimmune diseases like Rheumatoid arthritis (RA). The inappropriate immune response further triggers the cascade of inflammatory changes resulting in precipitation of symptoms and hampers quality of life (QOL). The underlying psycho-somatic component of the disease requires a holistic approach to its treatment dimension rather than the use of pharmacotherapy. The applicability of mind-body interventions has become essential in today's fast-paced life. Yoga, a mind-body technique, alters the mind's capacity to facilitate systemic functioning at multiple organ system levels. Hence, we conducted this study to evaluate the impact of 8 weeks of a yoga-based lifestyle intervention (YBLI) on psycho-neuro-immune markers, gene expression patterns, and QOL in RA patients on routine medical therapy. A total of 66 patients were randomized into two groups: yoga group or non-yoga group and were assessed for a panel of inflammatory cytokines (IL-6, IL-17A, TNF-α, and TGF-ß), mind-body communicative markers (BDNF, DHEAS, ß-endorphin, and sirtuin) and transcript levels of various genes (IL-6, TNF-α, NFKB1, TGF-ß, and CTLA4). We assessed disease activity and QOL using the DAS28-ESR and WHOQOL-BREF questionnaire, respectively. Yoga group observed significant improvements in the levels of markers, which influenced the psycho-neuro-immune axis (p < 0.001) with an estimated effect size from small to medium range. In the yoga group, there was a significant reduction in DAS28-ESR (p < 0.001) and improvement seen in the physical health, psychological, social relationships domains (p < 0.001) of QOL, except environmental (p > 0.05). The yoga group showed downregulation of IL-6, TNF-α, and CTLA4 and upregulation of TGF-ß. These results suggest that a decrease in disease activity after yoga practice is associated with a significant reduction in inflammatory cytokines, the elevation of mind-body communicative markers, and normalization of various transcript levels, which improved QOL. Thus the adoption of YBLI improves clinical outcome in RA, and decreases systemic inflammation by its beneficial effects on psycho-neuro-immune axis and normalization of dysregulated transcripts. Thus YBLI may be used for RA patients as an adjunctive therapy.

Impact of yoga based mind-body intervention on systemic inflammatory markers and co-morbid depression in active Rheumatoid arthritis patients: A randomized controlled trial.

BACKGROUND: Recovery of patients with rheumatoid arthritis (RA) depends on several physical and psychological factors, besides pharmacological treatment. Co-morbid depression adversely affects the outcome in RA. Usual medical therapies have a limited scope and fail to cure the psychological component of the disease. With advanced therapeutic options, achieving a state of remission has become the treatment goal, yoga based mind body intervention (MBI) may provide a holistic approach in its treatment dimension. Hence, MBIs are the need of hour as majority of diseases have a psychosomatic component. OBJECTIVE: To explore the effect of Yoga based MBI on disease specific inflammatory markers and depression severity in active RA patients on routine disease modifying anti-rheumatic drugs (DMARDs) therapy. METHODS: A total of 72 RA patients were randomized into 2 groups: yoga group (yoga with DMARDs) and control group (DMARDs only). Blood samples were collected pre and post intervention for primary outcome measurements of systemic biomarkers. Disease activity score 28, erythrocyte sedimentation rate (DAS28ESR) and health assessment questionnaire disability index (HAQ-DI) were used to assess disease activity and functional status respectively at pre and post intervention time-points. Secondary outcome, depression severity, was assessed by Beck Depression Inventory II scale (BDI-II) at 2 weekly intervals during 8 weeks of the study interventional plan. RESULTS: After 8 weeks of yoga based MBI, there was significant decrease in the severity of RA as seen by reduction in levels of various systemic inflammatory markers as well as in DAS28ESR (p-value <0.0001; effect size = 0.210) and HAQ-DI (p-value 0.001; effect size = 0.159). Also, yoga group experienced a statistically significant time dependent step-wise decline in depression symptoms over the period of 8 weeks as compared to control group (p-value <0.0001; effect size = 0.5). Regression analysis showed greater reduction in the scores of BDI-II with DAS28ESR (R2 = 0.426; p <  0.0001) and HAQ-DI (R2 = 0.236; p = 0.003) in yoga group. CONCLUSIONS: Yoga, a mind body intervention re-established immunological tolerance by aiding remission at molecular and cellular level along with significant reduction in depression. Thus in this severe autoimmune inflammatory arthritis with a major psychosomatic component, yoga can be used as a complementary/adjunct therapy.