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Monday, 29 May 2017

The Research and studies of Musculoskeletal disorders (MSDs): Rheumatoid Arthritis - The Causes of Abnormal autoimmune response

Kyle J. Norton, Master of Nutrients
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Musculoskeletal disorders (MSDs) are medical condition mostly caused by work related occupations and working environment, affecting patients’ muscles, joints, tendons, ligaments and nerves and developing over time. A community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home. Musculoskeletal pain was reported by 57% of those interviewed(1).

Types of Musculo-Skeletal disorders in elder(2)

1. Osteoarthritis
2. Gout
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
6. Osteoporosis
7. Low back pain
8. Fibromyalgia

                                                                  Rheumatoid Arthritis



Rheumatoid Arthritis is defined a chronic disorder as a result of inflammation, affecting mostly the flexible (synovial) joints and tissues and organs in the body. The disease affects more women than men and generally occurs after the ages of 40, causing diminished quality of life of many elders(1). According to CDC, Musculoskeletal disorders (MSDs) affects over 52 millions of adults in the US alone, including 294,000 children under age 18 with some form of arthritis or rheumatic conditions(2). Rheumatoid Arthritis can induced bone loss through elevating bone resorption without increasing bone formation(4). A cross-sectional population-based study of 1042 patients with rheumatoid arthritis showed that RA patients had an increased risk of death from various causes(4a).

The Causes of Abnormal autoimmune response

Rheumatoid arthritis is caused by immune dysfunction in attacking its own tissues, causing severe damage and inflammation of the joints, especially in the progresses to destruction of cartilage and bone. The causes of auto immune disorder is unknown, but some researchers expected the following.

Scientists in the study of Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis suggested that patients with abnormal gene expressions of interleukin (IL) -37,(32a), miR-573 on IL-6 production(33) and microRNA-203(34),... are associated to increased risk of rheumatoid arthritis.
Dr. Lee HM and the research team at the Osaka University said" Abnormal regulatory networks in the immune response and one marrow (BM) cells from RA patients, indicating that the BM is pathologically involved in RA"(35).

2. Abnormal lipid profile
Abnormal lipid profile in many cases is associated to the metabolic syndrome risk, especially in patient with type II diabetes(36). The University of California suggested that patient with rheumatoid arthritis are found to have a high expression of low-density lipoprotein (LDL) cholesterol driven by increases in cholesterol ester catabolism(37). Dr. Xue C and the research team at the People's Hospital of Peking University showed that the association of rheumatoid arthritis and an abnormal lipid profile may be contributed as a result of increased inflammation markers and autoimmune antibodies(38) or inflammatory changes in HDL-C and Lp(a) metabolisms(39).


3. Genetic susceptibility
Certain genetic variations inherited from a parent, may be involved in the expression of RA patient, some research insisted. The Immunochip custom SNP array of 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers found that people with certain gene of loci are found to have an increased risk of rheumatoid arthritis(40).
Genetic association of CCR5 promoter polymorphism also seems to play an important role in determining different forms of rheumatoid arthritis(41), according to the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. In fact, over expression of Aiolos polymorphisms(42), LRP3 rs35829419 polymorphism(43), Interleukin-6 promoter haplotypes(44),... are all found to induced certain human diseases, including rheumatoid arthritis.




4. Inflammatory and infectious connections
Chronic inflammation of the joint can result of thickens the synovium, of that affect the cartilage and bone within the joint. Dr. Liao F. and the the research team at the Wuhan University said" Rheumatoid arthritis (RA) is a common, systemic autoimmune disease which leads to destruction of the joint architecture and consequent disability"(46). According to Epidemiological studies, the prevalence of RA affects about 5% of the population are aged 50 years or older, involved the connection of infectious etiology with a complex inflammatory response(45).
T helper 17 cells (Th17), a major effector cells in several chronic inflammatory states, correlated with local and systemic parameters of inflammation may also be a causative link to the expression of patient with RA(47).


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References

(1) 8 Areas of Age-Related Change(NIH)
(2) Arthritis-Related Statistics(CDC)
(3) Valgus deformities of the feet and characteristics of gait in patients who have rheumatoid arthritis by Keenan MA1, Peabody TD, Gronley JK, Perry J.(PubMed)
(4) Serum Sclerostin Level Among Egyptian Rheumatoid Arthritis Patients: Relation to Disease Activity ,Bone Mineral Density and Radiological Grading by Mehaney DA, Eissa M, Anwar S, El-Din SF(PubMed)
(4a) Death rates and causes of death in patients with rheumatoid arthritis: a population-based study by Sihvonen S1, Korpela M, Laippala P, Mustonen J, Pasternack A(PubMed)

(32a) Insights into IL-37, the role in autoimmune diseases by Xu WD1, Zhao Y1, Liu Y2.(PubMed)
(33) miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis by Wang L1, Song G2, Zheng Y3, Wang D4, Dong H4, Pan J1, Chang X3.(PubMed)
(34) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation by Stanczyk J1, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley CD, Tak PP, Gay S, Kyburz D.(PubMed)
(35) Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis as revealed by DNA microarray analysis by Lee HM1, Sugino H, Aoki C, Shimaoka Y, Suzuki R, Ochi K, Ochi T, Nishimoto N.(PubMed)
(36) What is the consequence of an abnormal lipid profile in patients with type 2 diabetes or the metabolic syndrome? by Windler E1(PubMed)
(37) Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib by Charles-Schoeman C1, Fleischmann R, Davignon J, Schwartz H, Turner SM, Beysen C, Milad M, Hellerstein MK, Luo Z, Kaplan IV, Riese R, Zuckerman A,McInnes IB.(PubMed)
(38) [Association between systemic inflammation and autoimmunity parameters and plasma lipid in patients withrheumatoid arthritis].[Article in Chinese]by Xue C1, Liu WL, Sun YH, Ding RJ, Hu DY.(PubMed)
(39) Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation by Dursunoğlu D1, Evrengül H, Polat B, Tanriverdi H, Cobankara V, Kaftan A, Kiliç M.(PubMed)
(40) High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis by
Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P, Zhernakova A, Stahl E, Viatte S, McAllister K, Amos CI, Padyukov L, Toes RE, Huizinga TW, Wijmenga C,Trynka G, Franke L, Westra HJ, Alfredsson L, Hu X, Sandor C, de Bakker PI, Davila S, Khor CC, Heng KK, Andrews R, Edkins S, Hunt SE, Langford C, Symmons D; Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate; Wellcome Trust Case Control Consortium, Concannon P, Onengut-Gumuscu S,Rich SS, Deloukas P, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Ärlsetig L, Martin J, Rantapää-Dahlqvist S, Plenge RM, Raychaudhuri S, Klareskog L,Gregersen PK, Worthington J.(PubMed)
(41) Genetic association of CCR5 promoter single nucleotide polymorphism in seronegative and seropositiverheumatoid arthritis by Lima G1, Furuzawa-Carballeda J, Ramos-Bello D, Jakez-Ocampo J, Pascual-Ramos V, Núñez-Alvarez CA, Granados J, Llorente L.(PubMed)
(42) Overexpression of Aiolos in Peripheral Blood Mononuclear Cell Subsets from Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis by Cai X1, Liu X1, Du S1, Xu X1, Liu A1, Ge X1, Qiao Y1, Jiang Y2,3.(PubMed)
(43) NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans by Zhang Q1, Fan HW1, Zhang JZ1, Wang YM1, Xing HJ1.(PubMed)
(44) Interleukin-6 promoter haplotypes are associated with etanercept response in patients with rheumatoid arthritis by Schotte H1, Schmidt H2, Gaubitz M3, Drynda S4, Kekow J4, Willeke P5, Schlüter B2.(PubMed)
(45) Rheumatoid arthritis and periodontitis - inflammatory and infectious connections. Review of the literature by Rutger Persson G1(PubMed)
(46) Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associatedrheumatoid arthritis by Liao F1, Li Z, Wang Y, Shi B, Gong Z, Cheng X.(PubMed)
(47) The potential role of Th17 in mediating the transition from acute to chronic autoimmune inflammation:rheumatoid arthritis as a model by Ferraccioli G1, Zizzo G.(PubMed)