scholarly journals Vitamin D as a Principal Factor in Mediating Rheumatoid Arthritis-Derived Immune Response

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Muhammad M. Aslam ◽  
Peter John ◽  
Attya Bhatti ◽  
Sidrah Jahangir ◽  
M. I. Kamboh
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Autoimmune Disorder ◽  
Serum Levels ◽  
Principal Factor ◽  
Phosphate Homeostasis ◽  
Low Serum

Rheumatoid arthritis (RA) is a systemic multifactorial autoimmune disorder. The interactions between diverse environmental and genetic factors lead to the onset of this complex autoimmune disorder. Serum levels of vitamin D (VD) are involved in the regulation of various immune responses. Vitamin D is a key signaling molecule in the human body that maintains calcium as well as phosphate homeostasis. It also regulates the functions of the immune system and, thus, can play a substantial role in the etiology of various autoimmune disorders, including RA. Low serum VD levels have been found to be associated with a higher risk of RA, although this finding has not been replicated consistently. The molecular mechanisms by which VD influences autoimmunity need to be further explored to understand how variation in plasma VD levels could affect the pathogenesis of RA. This mini-review focuses on the influence of VD and its serum levels on RA susceptibility, RA-associated complexities, treatment, and transcriptome products of key proinflammatory cytokines, along with other cytokines that are key regulators of inflammation in rheumatoid joints.

scholarly journals Circulating Levels of Free 25(OH)D Increase at the Onset of Rheumatoid Arthritis

2019 ◽  
Author(s):  
Vidyanand Anaparti ◽  
Xiaobo Meng ◽  
Hemsekhar Mahadevappa ◽  
Irene Smolik ◽  
Neeloffer Mookherjee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Linear Regression Analysis ◽  
Autoimmune Disorder ◽  
Joint Inflammation ◽  
Epidemiological Studies ◽  
Vitamin D Metabolites ◽  
Serum Samples ◽  
Hs Crp ◽  
Circulating Levels

ABSTRACTObjectiveEpidemiological studies suggest vitamin D deficiency as a potential risk factor for rheumatoid arthritis (RA) development, a chronic autoimmune disorder highly prevalent in indigenous North American (INA) population. We therefore profiled the circulating levels of 25-hydroxyvitaminD [25(OH)D], an active metabolite of vitamin D, in a cohort of at-risk first-degree relatives (FDR) of INA RA patients, a subset of whom subsequently developed RA (progressors).Methods2007 onward, serum samples from INA RA patients and FDR were collected at the time of a structured baseline visit and stored at −20°C. Anti-citrullinated protein antibodies (ACPA), 25(OH)D, hs-CRP, vitamin-D binding protein (VDBP) levels were determined using ELISA and rheumatoid factor (RF) seropositivity was determined by nephelometry.ResultsWe demonstrate that 25 (OH) D concentrations were lower in winter than summer (P=0.0538), and that serum 25(OH)D levels were higher in samples collected and stored after 2013 (P<0.0001). Analysis of samples obtained after 2013 demonstrated that 37.6% of study participants were 25(OH)D insufficient (<75nmol/L). Also, seropositive RA patients and FDR had lower 25(OH)D levels compared to ACPA-/FDR (P<0.05, P<0.01 respectively). Linear regression analysis showed 25(OH)D insufficiency was inversely associated with presence of RA autoantibodies. Longitudinal samples from 14 progressors demonstrated a consistent increase in 25(OH)D levels at the time they exhibited clinically detectable joint inflammation, without any significant change in VDBP levels.ConclusionWe demonstrate that 25(OH)D levels in serum increased at RA onset in progressors. The potential role that vitamin D metabolites and their downstream effects play in RA transition requires further investigation.

scholarly journals AB1310 Anti-mÜllerian hormone and vitamin d serum levels in women with rheumatoid arthritis

2018 ◽  
Author(s):  
I. Perez Onofre ◽  
C.M. Skinner Taylor ◽  
L. Perez Barboza ◽  
M. Erguia Bernal ◽  
D.A. Galarza Delgado ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Serum Levels

scholarly journals Roles of Genes in the Susceptibility to and Severity of Rheumatoid Arthritis - A Review

1970 ◽  
Vol 13 (1) ◽  
pp. 51-54
Author(s):  
Abul Khair Ahmedullah ◽  
Shamim Ahmed ◽  
MD Ariful Islam
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Factors ◽  
Human Leukocyte ◽  
Drug Efficacy ◽  
Autoimmune Disorder ◽  
Individual Variability ◽  
Unknown Etiology ◽  
Entire Genome ◽  
Gene Effects ◽  
Leukocyte Antigen

Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. It is conceivable that there is more than one susceptible gene(s) operative in RA, and an interaction of the relevant genes may predispose the offspring to develop the disease under certain conditions .Outside the major histocompatibility complex (MHC) region, some additional risk loci have been identified and validated including PTPN22, STAT4, PADI4, CTLA4 and others Genetic factors are also important in RA pharmacotherapy due to the gene-dependent activity of enzymes involved in the pharmacokinetics and/or pharmacodynamics of RA medications. Indeed, there is great variability in drug efficacy as well as adverse events associated with any anti-rheumatic therapy and genetics is thought to contribute significantly to this inter-individual variability in response. The ability to screen the entire genome for association to complex diseases has great potential for identifying gene effects. DOI: http://dx.doi.org/10.3329/jom.v13i1.10048 JOM 2012; 13(1): 51-54

scholarly journals Which factors are associated with sarcopenia and frailty in elderly persons residing in the community?

2018 ◽  
Vol 21 (6) ◽  
pp. 755-766
Author(s):  
Ana Paula Pillatt ◽  
Rutiana Silva Patias ◽  
Evelise Moraes Berlezi ◽  
Rodolfo Herberto Schneider
Keyword(s):  
Systematic Review ◽  
Vitamin D ◽  
Frail Elderly ◽  
Serum Vitamin ◽  
Serum Levels ◽  
Elderly Persons ◽  
Risk Of Death ◽  
Increased Risk ◽  
Vitamin D Levels ◽  
Low Serum

Abstract Objective: to broaden knowledge about the factors associated with sarcopenia and frailty in elderly persons residing in the community. Method: an integrative systematic review based on the PRISMA recommendations was carried out, using articles published from 2012 to March 2017 in the PubMED, SciELO, Virtual Health Library, CINAHL and Springer electronic databases with the following descriptors: frail elderly, sarcopenia and etiology and their synonyms. The articles identified by the initial search strategy were independently assessed by two researchers, according to the eligibility criteria, and the articles selected were evaluated for methodological quality. Results: the results of this survey show that frailty may be associated with sarcopenia, low serum vitamin D levels, anemia, subclinical hyperthyroidism in men, while the greatest evolution in women was for osteoporosis. An association between sarcopenia and advanced age was also observed, with worsening quality of life, physical-functional capacity, nutritional status and comorbidities, as well as an increased risk of death in sarcopenic elderly persons. Conclusion: this systematic review showed that low serum levels of vitamin D are associated with frailty and factors that predispose this condition. It is therefore important to monitor the serum levels of this vitamin in the elderly population, and it is suggested that new studies are carried out related to supplements of this vitamin in frail elderly persons.

scholarly journals Dissecting the Molecular Mechanism of Wang-Bi Capsule in the Treatment of Experimental Rheumatoid Arthritis Based on Synovial Tissue Proteomic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Haiyang Shu ◽  
Yingjie Shi ◽  
Li Li ◽  
Ning Zhao ◽  
Cheng Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Proteomic Analysis ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Expression Levels ◽  
Matrix Metalloproteinase 3 ◽  
Cxcr4 Signaling ◽  
Wang Bi

Wang-Bi capsule (WB) is a traditional Chinese medicine formula and has been applied for rheumatoid arthritis (RA) treatment for many years. However, its underlying molecular mechanisms still remain unclear. In this study, collagen-induced arthritis (CIA) rats were used to observe the therapeutic effect of WB used at different time points, and the proteomic analysis of synovial tissue was applied to reveal its basic molecular mechanisms. The results demonstrated that WB not only effectively ameliorated the symptoms and synovitis, but also downregulated the serum levels of inflammatory cytokines/chemokines in CIA rats. Furthermore, the proteomic analysis of synovial tissue showed that WB could regulate several signaling pathways associated with inflammation or cell migration, such as “IL-1 signaling,” “IL-8 signaling,” and “CXCR4 signaling.” The expression levels of proteins including matrix metalloproteinase 3 (MMP3), MMP19, lipopolysaccharide-binding protein (LBP), serine/threonine kinase interleukin-1 receptor-associated kinase 4 (IRAK4), and actin-related protein 2/3 complex subunit 5 (ARPC5) in these pathways were downregulated significantly by WB when compared with the model group. In sum, this study indicated that WB had obvious inhibitory effects on synovitis of CIA rats, and the mechanisms of which may be involved in downregulating the expression levels of several key proteins including MMP3, MMP19, LBP, IRAK4, and ARPC5.

scholarly journals Genetic Factors and Molecular Mechanisms of Vitamin D and Obesity Relationship

2018 ◽  
Vol 73 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Francisco Javier Ruiz-Ojeda ◽  
Augusto Anguita-Ruiz ◽  
Rosaura Leis ◽  
Concepcion M. Aguilera
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Vdr Gene ◽  
Association Analyses ◽  
Hydroxyvitamin D ◽  
Wide Range ◽  
The Relationship

Vitamin D (vitD) deficiency is associated with a wide range of chronic diseases and conditions, including obesity, and with an increasing severity of metabolic dysregulation, such as insulin resistance, hyperlipidemia, liver disease, and hypertension, both in children and adults. However, the nature of the association between low vitD status and obesity remains unclear. This fact has motivated the scientific community to conduct genetic association analyses between 25-hydroxyvitamin D (25[OH]D)-related genes and obesity traits. In this line, the variation in the vitD receptor (VDR) gene represents the bulk of the findings. Specifically, polymorphisms in the VDR gene have been associated with obesity traits in some but not all, studies. Thus, results regarding this matter remain inconclusive. Other genes aside from VDR have also been investigated in relation to obesity-related traits. However, again, findings have been inconsistent. In general, results point to the fact that the DBP/GC gene could be an important protein-linking obesity and vitD status. On the other hand, several studies have attempted to determine the molecular mechanism of the relationship between 25(OH)-D levels and obesity. Some of these studies suggest that vitD, due to its fat-soluble characteristic, is retained by the adipose tissue and has the capacity to metabolize 25(OH)-D locally, and this can be altered during obesity. Additionally, vitD is capable of regulating the gene expression related to adipogenesis process, inflammation, oxidative stress, and metabolism in mature adipocytes. Therefore, the aim of the present review was to evaluate the association between obesity and vitD deficiency describing the main molecular mechanism of the relationship and the link with genetic factors. Key Messages: Low serum 25(OH)-D is positively associated with obesity or BMI in adults and children. Circulating vitD concentrations are, at least, partially determined by genetic factors. VitD plays an important role in the adipogenesis process and inflammation status in adipocytes and adipose tissue.

scholarly journals Effects of Biological Therapies on Molecular Features of Rheumatoid Arthritis

2020 ◽  
Vol 21 (23) ◽  
pp. 9067
Author(s):  
Chary Lopez-Pedrera ◽  
Nuria Barbarroja ◽  
Alejandra M. Patiño-Trives ◽  
Maria Luque-Tévar ◽  
Eduardo Collantes-Estevez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Adaptive Immune System ◽  
Autoimmune Disorder ◽  
Synovial Fibroblasts ◽  
Chronic Inflammatory Disease ◽  
Pharmacological Therapy ◽  
Biologic Dmards ◽  
Molecular Features ◽  
Specific Effects

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease primarily affecting the joints, and closely related to specific autoantibodies that mostly target modified self-epitopes. Relevant findings in the field of RA pathogenesis have been described. In particular, new insights come from studies on synovial fibroblasts and cells belonging to the innate and adaptive immune system, which documented the aberrant production of inflammatory mediators, oxidative stress and NETosis, along with relevant alterations of the genome and on the regulatory epigenetic mechanisms. In recent years, the advances in the understanding of RA pathogenesis by identifying key cells and cytokines allowed the development of new targeted disease-modifying antirheumatic drugs (DMARDs). These drugs considerably improved treatment outcomes for the majority of patients. Moreover, numerous studies demonstrated that the pharmacological therapy with biologic DMARDs (bDMARDs) promotes, in parallel to their clinical efficacy, significant improvement in all these altered molecular mechanisms. Thus, continuous updating of the knowledge of molecular processes associated with the pathogenesis of RA, and on the specific effects of bDMARDs in the correction of their dysregulation, are essential in the early and correct approach to the treatment of this complex autoimmune disorder. The present review details basic mechanisms related to the physiopathology of RA, along with the core mechanisms of response to bDMARDs.

Sign in / Sign up

Export Citation Format

Share Document