Samprapti vighatana of Autoimmunity w.s.r to RheumatoidArthritis

Introduction

Autoimmunity is a misdirected immune response that occurs when the immune system goes out of usual response and attacks the body itself. Autoimmunity is present in every individual to some extent and goes unnoticed and harmless but at the same time; it can cause a broad range of human illnesses, known collectively as autoimmune diseases. Autoimmunity develops when an immune response occurs against our own tissues. In auto immunity, there is an exaggerated response which is destructive in nature. It is also described in other words as Injury to self in an attempt of protection from self. Any disease that results from such aberrant immune response is termed an Auto immune disease.

Rheumatoid arthritis is the most common auto immune disease that is caused by the inappropriate activation of the immune system of the body and affects the joints instead. As a result the tissue that lines the inside of the joint, called the Synovium, develops inflammation and related swelling, pain and stiffness in the joints. If this process of inflammation is not checked, it can damage the elastic tissue that covers the ends of the bones in the joint, called - Cartilage. As the problem advances it can damage the bones themselves with loss of cartilage and joint space reduction. The joints become loose, painful and stiff leading to irreversible damage.

The most commonly affected joints in RA are that of the hands, feet, wrists, elbows, knees and ankles that may be symmetrical or unilateral. RA can also the systems other than joints such as the cardiovascular or respiratory systems. Rheumatism or Rheumatic disorder is a non-specific term for medical problems affecting the heart, bones, joints, kidney, skin and lung. Mostly, this term is used to focus on arthritis i.e. rheumatoid arthritis. However, ‘non-articular rheumatism’, also known as ‘regional pain syndrome’ or ‘soft tissue rheumatism’ can cause just as much discomfort and difficulty.

Rheumatoid arthritis is most important among these which can cripple an individual’s life that sometimes leads to destruction and ankylosis of affected joints.

Saitikartavyatarogotpadakahetu: The very cause that is capable of manifesting a disease is Nidana.

SampraptihJatihAagatih: From theNidana, the mode of Doshavigunata, Dhatudourbalya, Srotovigunata and complete manifestation of the vyadhi is called Samprapti.

Chikitsa is nothing but breaking the process of this Samprapti and restoring the harmony of Dosha and dhatu i.e., prakritisthapanai.e.Sampraptivighatana mevaChikitsa. Before venturing into management of any disease, it is therefore important to analyze and understand the mode of manifestation.

Aims and Objectives

In most of the recent literatures and research works available on Ayurveda, Rheumatoid arthritis is commonly considered as the disease Amavata that is first explained by Acharya Madhavakara. Taking into account an important point here that, the disease Amavata being not explained in detailed manner in any of the Brihatrayees, an attempt to understand the concept of Autoimmunity and rheumatism is done in the article.

At the same time analysis of SampraptiOF Autoimmunity is also done to have a clear approach towards the disease management.

Etiology of Rheumatism and autoimmunity: The specific causative factor for the disorder is still not understood. Postulations have supported the researchers to come to an understanding that some of the intrinsic factors make the body susceptible for abnormal activation of immune system and resultant inflammation. They are

1. Genes¹ - There's some evidence that rheumatoid arthritis can run in families, although the risk of inheriting the condition is thought to be low as genes are only thought to play a small role in the condition.Genetic factors contribute to the occurrence of RA as well as to its severity.

A first-degree relative of a patient of RA is 2–10 times likely than the general population.

“Yasyayasya hi avayavasya bijebijabhageva doshah prakopamapadyante, tam tam vikrutira vishati”.

2. Hormones – RA is more common in women than men, which may be because of the effects of the hormone estrogen, although this link hasn't been proven.

3. Smoking2 – Some evidence suggest that people who smoke are at an increased risk of developing RA.

4. Infectious agents³ like bacteria and viruses that trigger the process of inflammation and also can cause hormonal imbalance.

5. Obesity – The altered metabolism of adipose tissue that can give way to set the process of inflammation and lead to various autoimmune disorders.

6. Stress – Response to different kinds of stress and relative trauma, response to environmental stimuli also can lead to autoimmune responses in the body.

The etiological factors can also be categorized on the following headings based on their role in producing the inflammatory reaction

1.Manasahetu

2.Viruddhaahara + viruddhacheshta

3.Aharavidhiniyamaullanghana

4.Asatmyaahara

5.Asatmyabahyahetu ( Pradooshana, allergens like pollen/ ubiquitous antigens)

6.Dushivisha / Garavisha

7.Aushadhaupadrava

Role of T Cells⁴ :

• The intelligent cell called the T regulatory cell is produced in the thymus.

• Appropriate balance of T cells with proper ratio of T helper, cytotoxic T cells, killer T cells and T suppressor cells is required

• Test used to look at this balance is the CD4:CD8 test. T helper cells are in the CD4 category and the T suppressor cells are in the CD8 category.

• When the body has elevated T helper, cytotoxic and killer T cells, there is an increased risk of developing chronic inflammatory conditions and autoimmunity.

• On the flip side, if the body has elevated immune suppressor cells, the immune system lacks punch and the individual may be more susceptible to infection.

• In Rheumatoid arthritis a cascade of pathological events occur right from theactivation of T – cells. T – Cells trigger the synovial fibroblast triggering the macrophages.

• T- Cells activate the B – Cells to produce the autoantibody immune complexes including rheumatoid factor and immunoglobulin. This in turn attacks the articular and extra articular parts.

• Differentiation of naïve T cells into Th 17 (TH17) cells results in the production of IL-17, a potent cytokine that promotes synovitis.

• T – Cells also trigger macrophages followed by TNF- alpha.

• They produce the interleukins like the IL1, IL8, IL15,IL17, IL23 and VEGF

. This affects the endothelium of vessels, bone cells, chondrocytes and synovial fibroblasts.

These inflammatory mediators contribute to manifest pain, redness and edema.

Discussion

The host cell is victim here in pathogenesis of RA. The cellular homeostasis is disturbed as a result of recognition of the antigen that is infectious/ noninfectious, intrinsic/extrinsic. The invasion of the antigen- prerakahetu. As a response to disturbed homeostasis, cellular inflammation develops. Inflammation further leads to cell injury. This cell injury is nothing but DhatuviguNata. Disturbed homeostasis is SrotoviguNata/ khavaiguNya. Inflammation in the next stage is Srotodushti. Most of the times the Srotodushtiprakara is Sanga. Reduced ability of the cell to metabolic activity due to inflammation is balahrasa.The cellular ability for maintaining physiology itself is the optimal Bala. So reduction in bala or BalaHrasa begins as soon as the inflammation begins.

It is to be pondered upon certain factors that play significant role in manifesting the final stage of the disease. They are

1 .Effects of viruddha aahara:

Dehadha tupratya neekabhootanidravy anidehadhatubhih virodhama padyante, Viruddhaguna sannipatebhooyasah alpha avajeeyate. … (A. Chakrapani)

Conquer of the stronger over the weaker is the rule adopted by the tissue components of the body. In the fight against the antigen the stronger antibodies start dominating to produce symptom complex.

2.VYADHI AKSHAMA SHAREERA

Nacasarvanishareeranivyadhikshamatve samarthani bhavanti… All the bodies would not possess the same vyadhikshamata. It varies according to certain influencing factors like Desha kalasamyogaveeryapramanaatiyoga, etc. weaker the vyadhikshamata, stronger is the antigeneffect. The same Doshas attain the capability of destructing the body when they are influenced by morbidity, antagonistic activity and with deeper tissue involvement.

3.VIKARA VIGHATA BHAVA ABHAVA:

Major histocompatibility complex in genetically predisposed persons are part of VikaravighatakarabhavaAbhava. Autoantibodies and cell mediated immunity both participate in destructive process with help of cytokines; certain cytokines are Vatadharmeeya, pitta dharmeeya, Kaphadharmeeya. Therefore different consequences develop based on involvement of specific cytokines..

To mention as an example - The process of Auto immunity involves....

• Every cell / tissue is in constant change process

• Operated by Agniin Dhatus- it is dhatwagni

• Causes like ViruddhaAhara– resulting in dhatwagnimandya

• The continuous change process by Agni makes it incompetent.

• Faulty state of materials form - called Aama

• Ama + Dosha,

• Ama + Dhatu,

• Ama + Sthaanavishesha( likebastigatavikara + Uragatavikara in Good Pasteur Syndrome),

• Ama + Dosha + Dhatu( like in Urustambha) Like this variable pathognomonic events are present in autoimmune diseases.

4.Kaphavrita vyana vata :

The features of Kaphavritavata include – Gatraguruta, Stambha in all Sandhiasthi and Parvapradesha, restricted movements (reduced range of movement) Su Ni 1/39 In Rheumatoid Arthritis like disorders, the preliminary pathology that takes place is Avarana. KaphavritaVyanavata leads to the manifestation of the conditions with multiple inflammatory lesions involving joints and restricts the movements.

5.Shotha roga samprapti

Bahyasirahprapyayadaasrukpitta nisan doosha yateehavayuh, Tairbaddhamargahsatadavisarpa nutsedha lingam shvayathumkaroti… C chi 12 The accumulation of leukocytes in the synovium does not result from local cellular proliferation but rather from migration of leukocytes from distant sites of formation in response to expression of adhesion molecules and chemokines by activated endothelial cells of synovial micro vessels5 .

6.Pandu roga samprapti

In Panduroga, the features that are observed include… Shaithilya of the dhatus, gourava, teevra Ojakshaya Alparakta, alpameda, teevra doshadhaturadooshana, nihsaratashithilendriyata and vaaivarnya… C ch 16

7.Punaravartaka jwara lakshana:

Deenata,Shwayathu, glani, pandutam, naanna kamatam,Kandu,utkotha,pidaka, agnimandya, features are explained as manifestations in Punaravartakajwara. Evamanyeapicagadavyavartantepunargatah, AnirghatenadoshanamAlpairapiAhitaihnrunam In a recovery period from Jwara if the person indulges in the Nidana again it will lead to manifestation of Punaravartana of Jwara with the features similar to autoimmunity.

8.Bala – The matter that matters:

BALA the innate immune system plays significant role in identifying and antagonizing the antigen. Bala helps in providing -

a) Rapidly detects invading pathogenic microbes as foreign and eliminate them.

b) Toll-like receptors⁷ (TLR) – membrane receptors that sense extra cellular microbes and trigger anti pathogen signaling cascades.

c) Intra cellular sensors- NOD like receptors sense non-microbial danger signals.

9.Vidagdha ahara as pro – Inflammatory factor:

Vidagdhaahara alters the internal atmosphere of the intestines and also influences the gut microbiota. The intestines are the largest mucosal interface between the environment and us. Incompetent tight junctions cause increased intestinal permeability, commonly referred to as ‘leaky gut’ and can result in the absorption of incompletely digested protein and antigens. Then they over stimulate the immune system through the bloodstream. Small intestinal bacterial overgrowth SIBO is high likely hood of generating leaky gut- which causes Ahara Shuktata⁸

10.Process of inflammation inside the cell

The inside of the cell undergoes tremendous change in response to inflammatory activity.

• Inflammasomes⁹ - Intracellular protein complexes that enable autocatalytic activation of inflammatory caspases.

• They drive host and immune responses by releasing cytokines and alarmins into circulation by inducing pyroptosis- a proinflammatory cell death mode.

• They link the sensing of microbial products and metabolic stress to the proteolytic activation of Proinflammatory cytokines IL-1beta and IL-18.

11.Cic and Autoimmunity

In chronic inflammatory conditions (CIC)10 - Tissue damage resulting as an indirect effect of the inflammatory process.In autoimmunity - Tissue damage develops as a direct effect of the inflammatory process.This is why one can see AsanjataBalapurusha after recovery from a vyadhibecoming prone to develop inflammation.

Management:

Management of autoimmunity demands multidimensional and multi-factorial approach. The summery of the same could be drawn as follows.

1.Nidanaparivarjana–

The cellular homeostasis is Bala and it is the benchmark. It is reduced by any nidana. Balahrasa begins with any nidanasevana. Nidana acts in 3 levels.

i) Doshavriddhikara/ kopakara

ii) Dooshyadourbalyakara

iii) And khavaiguNya Kara.

3 couplets of nidana are identifiable namely,

i) Viruddhaahara+ chesta

ii) Mandagni + nischalatwa

iii) Snigdhabhukta+ vyayama

2.Amapachana, Srotoshodhana, Agni deepana –

Amavatachikitsa sutra is to be invariably adopted in treatment of autoimmunity. It is to be noted that the chikitsa for Amavata is framed taking in to consideration of Ama, Jwara and Vata.

Langhanamswedanamtiktadeepananikatoonica, Virechanamsnehapanambastayashcamamarute. ..(Y. R)

Particularly, here jwara sutra has some specialityKatu rasa and rukshaswedathat denote severity of Ama. These 2 factors are important in doing Amapachana, Shoshana and even Mala Nirharana.

Intestinal permeability or leaky gut syndrome¹¹ is a condition where the intestinal lining is damaged. The damage to the gut lining opens up the intestinal junctions and allows for large food particles, bacteria and environmental toxins to seep into the blood stream.

When the immune system recognizes that bacteria and large undigested food particles are in the blood stream, it will go on high alert, as this could be a life threatening risk. So the body initiates a chronic inflammatory process in order to reduce the bacteria, toxic debris or food particles in circulation¹². Keeping the gut lining healthy is of upmost importance to establishing immune tolerance and heal autoimmune disease.

3. Chikitsa for the respective srotas that is involved in the Samprapti –

In autoimmune disorders there is always a multi system involvement found. SaptaDhatu and Mahasrotas are at the brunt of being affected.

4.Shodhana Karma/ Nityavirechana-

Toxins and Detoxification Ability of the body: The modern world is full of environmental toxins and these play a role in the development of autoimmune conditions. There are over 500 chemicals stored in our body and the average individual has at least seven pesticides tested in their urine. It is imperative to have a daily detoxification lifestyle to get these unwanted toxins out of our system¹³.

The body has a built-in metabolic detoxification system to address this problem by converting fat soluble toxins into inactive water soluble metabolites. (Function of apana). This process is carried out by a series of enzymes that transform, conjugate (attach) and transport the toxins out of the body. Induced Shodhana karma or Nityavirechana karma will support this mechanism and detoxification is accelerated aiding into faster recovery.

Many individuals have genetic polymorphisms that hamper their ability to detoxify. Others have had their detoxification systems overwhelmed resulting in low glutathione and methylating elements. (Buddhi and Smriti in the cell). Without these key factors, these individuals are unable to adapt and detoxify which allows oxidative stress and inflammation to be amplified. To enhance or to improve the cellular level memory, the body and mind must undergo training for proper life style and appropriate exercise. Regular practice of Yoga and meditation are capable of improving cellular memory and thus minimize the impact of genetical factor in causing the autoimmunity.

5.Jwarachikitsa :

Jwara or pyrexia with malaise, and malady is an invariable feature of auto immunity as a result of inflammation. Reducing fever will improve the tissue permeability and clears the detoxification process.

6.Shothaharachikitsa: The key to reducing inflammation and autoimmunity is to improve the immune coordination within our body in order to establish immune tolerance. Immune tolerance is where the body is able to effectively discriminate against self-vs.Non-self-tissue and is able to create a more precise inflammatory process so as to not have significant collateral tissue damage

7.Panduroga Chikitsa: All the Dhatuare under stress caused due to inflammation. The Dhatukshaya begins as the Samprapti of the disease is established. So alparaktoalpamedaskonihsaroshithilendriyah. Panduroga is a disease with Dhatukshaya, Dhatushithilata and Indriyadourbalya. These are the key features in chronic inflammatory conditions or autoimmunity.

8.Balavriddhikarachikitsa/ Rasayana: As result of inflammation the balakshaya begins as vyaktavastha. So it is set on in the beginning itself. Very much pronounced after inflammation creating the vicious cycle. Our aim of chikitsa is to break this cycle (sampraptivighatana) and Karyaphala should be setting back the homeostasis. / Prakritisthapana. Balam hi alamnigrahayadoshanam, bakakrutca tat. Bala is the cumulative integrity of SaptaDhatu. So prashastadhatu production –by using Rasayana leads to rectify the Balajanyavikaraautoimmunity. Specifically Rasa dhatu must be considered for correction as it is Rasa that produces PrakritaShleshama. Shleshma in prakrita avastha is Bala and vikrita avastha is Mala. Vikrutashleshma and vikrutamala rupashleshma have striking resemblance with that of Ama both being Nana varna and Atipicchila. Thus in autoimmunity Langhana, Balya and Rasayanadravyas would help in the management. Vitamin D, Glutathione, Omega 3 fatty acids¹⁴, Zinc and probiotics are considered to be the best healing factors in auto immunity. Glutathione¹⁵ is considered the “master antioxidant” within the body and is produced by every cell in the body where it functions to protect our DNA. Glutathione is our cell’s security guard that protects the cellular components from outside free radical attack. Longevity scientists now believe that the level of glutathione in our cells has a direct relationship with how long we will live. Glutathione plays a very important role in establishing immune tolerance. Studies have demonstrated that glutathione enhances the function of T cells and modulates immune activity. In this way, optimizing glutathione levels are extremely important for reducing collateral damage associated with inflammation and autoimmune reactions.

Conclusion:

The concept of Autoimmunity is very well understood by applying Ayurvedic concepts. Though the matter seems to be scattered in the texts, clarity is brought by proper logical analysis. Autoimmunity and rheumatism do not fit under one single heading, but various concepts like Bala, Vyadhikshamata, Panduroga, Jwara, Shotha, Beejadosha, and Avritavata appropriately synchronized together will help to decipher the phenomenon.