A comparison between femoral neck and LS-BMD with LS-TBS in T2DM patients: a case control study.

BACKGROUND: Despite having higher bone mineral density (BMD) values, type 2 diabetes mellitus (T2DM) patients are at increased risk of fracture. Trabecular bone score (TBS) obtained by evaluating bone microarchitecture might be a more accurate factor for determining bone strength in T2DM patients. In this study, we aimed at investigating the mean values of lumbar spine (LS) TBS, LS-BMD, and femoral neck BMD in T2DM patients and controls, as well as the ability of LS-TBS and BMD in distinguishing between T2DM patients and controls. METHODS: This case-control study was conducted on 150 patients with T2DM (129 women, 21 men) and 484 controls (424 women, 60 men) in Tehran, Iran. LS-TBS along with femoral neck BMD and LS-BMD was computed using dual-energy X-ray absorptiometry images. Diagnostic accuracy and discriminative capacity of LS-TBS, femoral neck BMD, and LS-BMD between the case and control groups were assessed. RESULTS: T2DM patients showed significantly lower LS-TBS values compared to the control group in the total population and in women. However, in T2DM patients, femoral neck BMD and LS-BMD were found to be significantly higher in the total population and in men, respectively, compared to the control group. Based on area under the curve (AUC) and after adjusting for age and BMI, TBS, LS-BMD, and femoral neck BMD were shown to have the acceptable ability in distinguishing T2DM patients and controls. CONCLUSION: Besides higher BMD and lower TBS values in T2DM patients compared to controls, a similar acceptable discriminative ability of LS-TBS, LS-BMD, and femoral neck BMD in differentiating between T2DM patients and controls was observed in the total population and in women.

Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19.

BACKGROUND: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. OBJECTIVE: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. METHODS: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. RESULTS: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). CONCLUSIONS: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.

The role of ß-d-mannuronic acid, as a new non-steroidal anti-inflammatory drug on expression of miR-146a, IRAK1, TRAF6, NF-κB and pro-inflammatory cytokines following a clinical trial in rheumatoid arthritis patients.

Context: miR-146a, its targets (IRAK1, TRAF6) and NF-κB transcription factor play a fundamental role in rheumatoid arthritis (RA). Positive effects of drug ß-d-mannuronic acid (M2000) were proven on their expression in the HEK-Blue hTLR2 cell line, and results of its phase III clinical trial on RA patients were encouraging.Objective: This research aimed to investigate the effects of M2000 on expression of these genes and serum levels of IL-6 and TNF-α as pro-inflammatory cytokines in RA patients.Material and methods: In this study (Trial Registration Number: IRCT2017100213739N10), 12 RA patients (according to the American College of Rheumatology criteria) and 12 healthy subjects (as control group) were selected. The gene expression of miR-146a, IRAK1, TRAF6, and NF-κB were measured at the baseline and after 12 weeks M2000 therapy, using quantitative real-time PCR method. Moreover, the serum levels of IL-6 and TNF-α were evaluated at the similar times by ELISA method.Results: Our findings showed that the gene expression of miR-146a, IRAK1, TRAF6, and NF-κB significantly decreased after 12 weeks M2000 therapy in RA patients (0.81-, 0.68-, 0.79-, 0.82-fold, with p < .05, p < .01, p < .01, p < .05, respectively). Furthermore, the serum levels of IL-6 and TNF-α significantly reduced in these patients after 12 weeks M2000 therapy (both with p < .05).Conclusions: The present research results determined the part of molecular mechanisms of drug M2000 in RA treatment, based on the expression and function modification of miR-146a, IRAK1, TRAF6, NF-κB, IL-6 and TNF-α.

Immunopharmacological effect of ß-d-mannuronic acid (M2000), as a new immunosuppressive drug, on gene expression of miR-155 and its target molecules (SOCS1, SHIP1) in a clinical trial on rheumatoid arthritis patients.

The positive impacts of ß-d-mannuronic acid (M2000) on the gene expression of miR-155, its target molecules (SOCS1 and SHIP1), and NF-κB transcription factor were demonstrated in a study using the HEK293-TLR2 cell line. This new drug has been approved as a safe and effective medication by a randomized, multinational, phase III clinical trial on RA patients. The present study aimed to evaluate the oral administration effect of M2000 on the expression levels of the mentioned genes in RA patients. This research was conducted on 12 RA patients and 12 healthy individuals. After extraction of total RNA from PBMCs of patients and synthesis of cDNA, the expression levels of miR-155, SOCS1, SHIP1, and NF-κB genes were measured through quantitative Real-time PCR at baseline and after 12 weeks of M2000 therapy. Our findings showed that the miR-155 gene expression level significantly decreased in the M2000-treated patients compared with the baseline (0.76-fold, with p < .05). The expression levels of SOCS1 and SHIP1 genes significantly increased in the patients treated with M2000 compared with the before treatment (1.46-, 1.54-fold, with p < .01, p < .05, respectively). In addition, it was found that the gene expression level of the NF-κB transcription factor significantly reduced in M2000-treated patients compared with the baseline (0.81-fold, with p < .05). This study showed that the oral administration of M2000 was able to reduce the expression of the miR-155, increase the expression of SOCS1 and SHIP1, and decrease the NF-κB gene expression (Trial Registration Number: IRCT2017100213739N10).

International multicenter randomized, placebo-controlled phase III clinical trial of ß-D-mannuronic acid in rheumatoid arthritis patients.

BACKGROUND: The oral administration of drug ß-D-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. METHOD: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. RESULTS: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. CONCLUSION: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of ß-D-mannuronic acid as a new highly safe and efficient drug in the treatment of RA.

The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial.

OBJECTIVE: Previous studies have shown that the bioflavonoid quercetin has anti-inflammatory and anti-nociceptive effects. We investigated the effect of quercetin supplementation on inflammation, disease severity, and clinical symptoms in women with rheumatoid arthritis (RA). METHODS: The present study was a randomized, double-blind, placebo-controlled clinical trial in which 50 women with RA were allocated into a quercetin (500 mg/day) or placebo group for 8 weeks. Plasma levels of high-sensitivity tumor necrosis factor-α (hs-TNFα), erythrocyte sedimentation rate (ESR), clinical symptoms including early morning stiffness (EMS), morning and after-activity pain, and tender (TSC) and swollen joint counts (SJC) were determined. Disease activity and functional disability were assessed by Disease Activity Score 28 (DAS-28), physician global assessment (PGA), and a health assessment questionnaire (HAQ) at the beginning and end of the study. RESULTS: Quercetin supplementation for 8 weeks significantly reduced EMS, morning pain, and after-activity pain (p < 0.05). DAS-28 and HAQ scores decreased in the quercetin group compared to placebo and the number of patients with active disease significantly decreased in the quercetin group. Plasma hs-TNFα level was significantly reduced in the quercetin group compared to placebo (p < 0.05). There were no significant differences in TJC and SJC between groups but TJC significantly decreased in the quercetin group after the intervention. Supplementation had an effect on ESR but it was not significant (p > 0.05). CONCLUSIONS: Five hundred milligrams per day quercetin supplementation for 8 weeks resulted in significant improvements in clinical symptoms, disease activity, hs-TNFα, and HAQ in women with RA.

Comparison of three different osteoporosis risk assessment tools: ORAI (osteoporosis risk assessment instrument), SCORE (simple calculated osteoporosis risk estimation) and OST (osteoporosis self-assessment tool).

BACKGROUND: SCORE, OST and ORAI risk assessment tools could reduce the cost burden of BMD tests by selecting the high risk patients to osteoporosis. In this study we compared the ability of these risk assessment measures to assess probability of the osteoporosis among post-menopausal women. METHODS: 211 post-menopausal women aged 45-88 years enrolled into the study. All of the patients underwent BMD test and divided into two groups according to T-Score level. 43 patients (20.4%) had T-Score ≤-2.5 (osteoporotic) (group-1) and 168 (70.6%) patients had T-Score of > -2.5 (non-osteoporotic). Among 168 nonosteoporotic cases, 88 had -2.5≤T-Score≤-2 in at least one bony area. These 88 cases in addition to the 43 cases with -2.5≤T-Score considered as high risk group to osteoporosis (group 2). Afterward, SCORE, OST and ORAI risk scores were calculated and sensitivity, specificity, likelihood ratio, accuracy index and area under the curve of each tool were determined in both groups and then compared with each other. RESULTS: SCORE had the highest sensitivity compared with others in both groups (95% and 88.2% respectively). Moreover, it had the highest diagnostic odds ratio and negative predictive value between the three methods. OST had the highest likelihood ratio and specificity in both groups (71.4% and 75.4%). There was significant difference between the sensitivity and specificity of the tests (p= 0.004 and 0.027). CONCLUSION: OST with the highest specificity and positive LR had a special role in determining the osteoporotic patients and SCORE with the highest sensitivity and negative predictive value had an exceptional role in exclusion of the non- osteoporotic individuals. However, considering the area under the curve, there was no significant difference among these three methods in determining osteoporosis.

Assessing rheumatologists and radiologists agreement rate regarding the diagnosis of focal bone erosions and osteopenic changes using hand X-rays radiography in patients with rheumatoid arthritis.

In rheumatoid arthritis, diagnosis of bone erosions and osteopenic changes in earlier stages is extremely important to the initiation of specific and more aggressive treatment to subsidize the disease, decrease morbidities, and increase patients' quality of life. In the present study, we assessed consensus rate of rheumatologists and radiologists regarding the detection of radiographic changes of hand in rheumatoid arthritis. Ninety-six adult patients with documented rheumatoid arthritis referring to our outpatient rheumatology clinic during March 2009-2010, enrolled into this cross-sectional study. Hands and wrists X-ray obtained for all patients. The films were observed by a rheumatologist and a radiologist separately, to detect focal bone erosions, periarticular osteopenic changes, and joint space losses. Agreement rates between the two specialists were assessed using the kappa test ratio. A total of 96 patients comprising 86 (89.5%) female and 10 (10.41%) male with a mean age of 48.5 ± 1.2 years (range 22-76 years old) were studied. The proportion agreement between the radiologist and rheumatologist regarding bone erosions and juxta-articular osteopenic changes was 69.7 and 84.3%, respectively. The kappa agreement coefficient for the diagnosis of bone erosions was 36% which showed significant poor agreement between two specialist (p < 0.001, proportion agreement = 69.7%). As well, the kappa of 20% for the detection of juxta-articular osteopenic changes revealed significant poor agreement between the two specialist (p < 0.047, proportion agreement = 84.3%). The results of the present study demonstrate that there is a minimal agreement between the two radiology and rheumatology specialists regarding simultaneous diagnosis of bone erosions and periarticular osteopenic changes in rheumatoid arthritis patients that emphasis requiring both specialists' X-ray report at the time of diagnosis.

Granulomatosis with polyangiitis with salivary glands involvement: Presenting a case and describing its clinical, pathophysiological, and therapeutic aspects.

Granulomatosis with polyangiitis (GPA), a rare form of small vessel vasculitis, may be manifested by multisystem involvement misleading its definitive diagnosis. The involvement of salivary glands is a very rare characteristic of GPA. Herein, we described a case of GPA with submandibular salivary gland involvement followed by reviewing the literature on similar cases. The case was a 31-year-old man, a known case of seronegative peripheral arthritis that referred recently with bilateral enlargement of the parotid and submandibular glands. Pulmonary nodules were also evident in the patient's CT scan. Fine-needle aspiration under ultrasound guidance indicated the presence of degenerated squamoid cells, giant cells, and inflammatory cells with a priority of neutrophils in the submandibular gland, as well as the presence of a cyst containing fluid without the evidence of malignancy in the parotid gland. The positivity for the Anti-neutrophil Cytoplasmic Antibody (C-ANCA) marker was also revealed. The patient was treated with methotrexate, prednisolone, and rituximab which led to a gradual reduction in the size of the glands and the improvement of the patient's clinical symptoms within 1 month after the treatment. Enlargement of salivary glands in the context of inflammatory disorders can raise doubts about the existence of GPA, and therefore imaging evaluation and histopathological assessment with an ANCA test will be necessary to confirm or rule out it.

Hemophagocytic lymphohistiocytosis accompanying Still's disease: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare hematologic disease that occurs due to immune system dysfunction. Clinical manifestations of this disease are fever, increased ferritin level, cytopenia, and hemophagocytosis in the biopsy report of the bone marrow. We report a 36-year-old woman referred to our hospital with persistent fever, arthralgia in interphalangeal joints, and cutaneous rash on the trunk, was subsequently diagnosed as an adult-onset Still's disease (AOSD), and after bone marrow aspiration, HLH was diagnosed with her.

Lupus Anticoagulant Is Associated with Critical Cases and High Mortality in COVID-19: A Literature Review.

Background: In severe COVID-19 cases, a hypercoagulable state may occur. Antiphospholipid syndrome-related auto-antibodies (APSRAs) contribute to coagulopathy, but their role in COVID- 19 remains unclear. We aimed to investigate the prevalence of positive APSRAs and their effect on clinical outcomes in confirmed COVID-19 patients. Materials and Methods: In this cross-sectional study, severe hospitalized COVID-19 cases were enrolled. Demographic and clinical data were obtained from the day of admission. APSRAs including IgG and/or IgM anticardiolipin (aCL) and anti-ß2-glycoprotein1 (anti-ß2GP1) as well as lupus anticoagulant (LAC) were measured. Results: In this study, 54 severe COVID-19 cases with positive RT-PCR and chest CT scans were recruited. Positive APSRAs were found in 7 (12.9%) patients. Positive LAC was a more prevalent marker as compared to other tests (11.1%). The prevalence of positive aCL (IgM or IgG) and anti-ß2 GPI (IgM or IgG) was 1.8% (in an elderly woman). Lower oxygen saturation was found in the positive APSRAs group as opposed to the negative APSRAs group (70.3±9 vs. 84.8±9.7%). The mortality rate in the positive APSRAs group was significantly higher relative to the negative APSRAs group (83.3% vs. 27.1%; P-value: 0.01). Likewise, the mechanical ventilation requirement in the positive group was also higher (50% vs. 27.1%, P-value: 0.28). Conclusion: This study indicated that LAC might be associated with critical cases and high mortality of COVID-19. Nonetheless, the mortality was not related to macrothrombotic incidence.

Developing A Minimum Data Set for A Rheumatoid Arthritis Registry in Iran.

Background: Using Minimum Data Set (MDS) is the first step in creating and developing a health care information system; it includes standard and key data elements to capture and manage patient care. Aims: This study aimed to develop an MDS in order for using it for designing registry of patients with rheumatoid arthritis in Iran. Methods: This study was conducted at two stages in 2018. In stage one, qualitative method and semi-structured interview were used to identify the registry data elements of patients with rheumatoid arthritis. Collected data was analysed using content analysis method. In stage two, using Delphi method, the developed data set was revised and validated by 15 rheumatologists. Descriptive statistics using SPSS software was used to analyse the data in Delphi. Results: The final MDS included 22 data elements, which were divided into two major categories of management data (including demographic data, and admission and discharge) and clinical data (including patient examination, treatment plans, and medication prescribed by physician). Conclusion: Minimum data set is one of the standard data collection tools playing an important role in health care data management. This study presented a MDS as a platform for creating a rheumatoid arthritis registry system in Iran recommended by rheumatologists.

Evaluating Mannuronic Acid Effect on Gene Expression Profile of Inflammatory Mediators in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a multisystem disorder. Various studies have shown the important role of inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-22, MYD88, and toll-like receptor 2 (TLR2) in this disease. In this study, we investigated the anti-inflammatory effects of B-D-Mannuronic acid (M2000), as a new immunosuppressive drug, on the expression of these inflammatory markers in peripheral blood mononuclear cells (PBMCs) of RA patients. The blood samples of active RA patients and healthy volunteers were used for PBMCsl separation. The cells were cultured with LPS (1 µg/mL), low (5 µg/mL), moderate (25 µg/mL), and high (50 µg/mL) doses of M2000 and a single dose of diclofenac (1 µg/mL) to evaluate TNF-α, IL-6, IL-22, MYD88, and TLR2 genes expression by quantitative real-time (qRT-PCR). Cell surface expression and MFI of TLR2 were assessed; using flow cytometry. Our findings exhibited a significant reduction of TNF-α, IL-6, and MYD88 gene expressions after treatment with three doses of M2000 and an optimum dose of diclofenac. TLR2 gene expression was significantly diminished by moderate and high doses of M2000 and a single dose of diclofenac. Moreoversurface expression of TLR2 was significantly downregulated by moderate and high doses of M2000, while MFI of this receptor was significantly reduced by three doses of M2000. The results of this research showed that M2000 was able to significantly reduce the gene expression of inflammatory molecules  TNF-α, IL-6, MYD88, and TLR2 in patients PBMCs. factor-alpha; Rheumatoid arthritis. These data revealed a part of the molecular mechanisms of M2000 in the treatment process.

Comparison of bone mineral density in forearm and hip regions and evaluation of area of these 2 sites.

Introduction: Osteoporosis is a common disease among middle-aged and older people. Because bone mineral density (BMD) is obtained by dividing bone mineral content by area, accurate measurement of the surface of the studied area plays an important role. Therefore, the purpose of this study was to investigate the area of the hip and forearm regions based on gender and height. Methods: In a cross-sectional descriptive study of 758 individuals (702 female and 56 male, divided into 2 groups of ≥50 years old and <50 years old), experienced personnel performed densitometry of the forearm and femur using a Hologic device. The results were statistically analyzed using SPSS software version 21. Results: In women ≥50 years old who were of white race, one-third of the forearm BMD showed moderate agreement with the femoral neck BMD, and in this group, total forearm BMD showed moderate agreement with the femoral neck BMD. In women <50 years old of Caucasian race, one-third of the forearm BMD showed good agreement with the femoral trochanter. In the same group of individuals, total forearm BMD also showed very good agreement with the femoral trochanter. In women <50 years old of white race, one-third of the forearm BMD showed good agreement with all 4 regions in the femur (trochanter, intertrochanteric, neck, total), and in the same group of individuals, total forearm BMD showed very good agreement with all 4 regions of the femur. Conclusion: According to the results obtained for comparison of forearm one-third with hip areas, it seems that simultaneous measurement of the forearm one-third area and different hip areas increases the accuracy of total BMD measurement.

Study of the Effects of N-acetylcysteine on Inflammatory Biomarkers and Disease Activity Score in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is considered as an autoimmune-related condition in which the overproduction of pro-inflammatory cytokines leads to an inflammatory cascade. N-acetylcysteine (NAC) is a potent anti-inflammatory and anti-oxidant agent. We aimed to explore the impact of oral NAC on cytokines activities and clinical indicators in RA patients. In this placebo-controlled randomized double-blind clinical trial, 41 active RA patients were allocated in either NAC (600 mg, twice a day) or placebo group, as add-on therapy to the routine regimen, for 8 weeks. Disease activity score with an erythrocyte sedimentation rate (DAS28-ESR), and serum concentrations of interleukin (IL)-1ß and IL-17 were assessed at baseline and end of the trial for all participants in the test and control groups. The reduction of the DAS28-ESR was higher considerably in the NAC group compared to that of the control group. No statistically significant differences were seen in the reduction of IL-1ß and IL-17 cytokines between the NAC and control groups. In addition, improvements in the patient global assessment, number of tender joints, number of swollen joints, and the ESR rates were in favor of the NAC group. Our findings reveal that NAC may have a beneficial effect on all of the clinical features of RA. However, non-significant variations in the IL-1ß and IL-17 levels suggest an alternative way of NAC effectiveness without influencing the measured cytokines. Nevertheless, these results need to be confirmed by further investigations.

Influence of ß-D-mannuronic Acid, as a New Member of Non-steroidal Anti- Inflammatory Drugs Family, on the Expression Pattern of Chemokines and their Receptors in Rheumatoid Arthritis.

BACKGROUND: Based on the encouraging results of phase III clinical trial of ß-Dmannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. METHODS: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 µg/mL) of M2000 and optimum dose (1 µg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. RESULTS: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression was downregulated significantly followed by the treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after the treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by the treatment of these cells with a high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by the treatment of these cells with a high dose of M2000 and optimum dose of diclofenac. CONCLUSION: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

Dermatomyositis-lupus overlap syndrome complicated with cardiomyopathy after SARS-CoV-2 infection: A new potential trigger for musculoskeletal autoimmune disease development.

COVID-19 should be considered as a new triggering factor for autoimmune disorders like DM-lupus overlap syndrome. We recommend that patients presenting with dermatomyositis during this pandemic be screened for COVID-19.

The Situation of Chemokine Ligands and Receptors Gene Expression, Following the Oral Administration of Drug Mannuronic Acid in Rheumatoid Arthritis Patients.

BACKGROUND: Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis (RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient and motivating results of international Phase III clinical trial of ß-D-Mannuronic acid (M2000) patented EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was designed. OBJECTIVES: This study aimed to assess the oral administration effects of this new drug on gene expression of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and CCL2/MCP-1 in PBMCs of patients with active form of RA. METHODS: Twelve patients suffering from RA, with inadequate response to conventional drugs were selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated to them for 12 weeks. The mRNA expression of target molecules was then evaluated in PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared to healthy controls. Patents related to this study were also reviewed. RESULTS: The results showed that M2000 was able to significantly down-regulate the mRNA expression of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments in the patients. CONCLUSION: Taken together, the results of this investigation revealed the part of molecular and immunological mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine ligands and receptors mediated processes.