Cigarette smoking and risk of adult-onset Still disease: a propensity score matching analysis.

BACKGROUND: Environmental factors play an important role in the pathogenesis of rheumatic diseases. Smoking is thought to be a risk factor for autoimmune rheumatic diseases. AIMS: The purpose of the present study was to assess the association between smoking and adult-onset Still disease (AOSD) and the effect of smoking on outcomes of this disease. METHODS: In this case-control study, patients with AOSD who met the Yamaguchi criteria, were older than 16 years at the disease onset and were in follow-up for at least 12 months were consecutively enrolled in the study. The outcome of AOSD was assessed by acquiring remission on treatment, remission off treatment, time to remission and rate of flare. The smoking status of participants was defined by direct or phone interviews. Individuals who had smoked daily for at least 6 months were defined as a smoker. We performed propensity score matching analyses by using four parameters, including age, sex, educational status and marital status. RESULTS: Propensity score matching resulted in 72 patients with AOSD and 216 matched controls. The number of ever smokers in the AOSD and control groups were 11 (15.3%) and 25 (11.6%) respectively. There was no significant increase in the risk of AOSD in multivariate analysis after adjustment for age, sex, marital status and educational level. There were no significant differences in the outcomes of AOSD between ever and never smokers. CONCLUSIONS: Smoking probably is not a risk factor for AOSD and did not affect the response to treatment.

Long-term remission in patients with systemic lupus erythematosus.

BACKGROUND: Remission has been introduced as a desirable outcome and the primary target of treatment in systemic lupus erythematosus (SLE). The purpose of this study was to identify the number of patients in remission and the long-term outcome of the disease and their predictors. METHOD: Of the 379 patients in our SLE Database, a total of 193 patients fulfilled the inclusion criteria. Remission was definition according to the definitions of remission in SLE. Three levels of remission were defined, including remission on-treatment, remission off-treatment and complete remission. In addition, we have defined a sustained remission for each level of remission in which the remission should last at least 5 years. RESULTS: During a median follow-up of 96 months, remission on-treatment and off-treatment, and complete remission were obtained in 49.2%, 38.9% and 19.2% of patients, respectively. Predictors of remission on-treatment in multivariate regression analysis were adherence to therapy and remission induction during 6 months after treatment. Predictors of remission off-treatment were age ≥40 at the time of analysis and remission induction during 6 months after treatment. Poor outcome (SLE Damage Index ≥1) was observed in 28% of the patients. Age at disease onset <30, kidney and nervous system involvement and SLEDAI-2K ≥ 11 at the cohort entry were the risk factors of poor outcome in multivariate analysis. However, sustained remission on-treatment had a negative association with poor outcome. CONCLUSION: Treatment with glucocorticoids, antimalarials, immunosuppressants and biologics in sequential or in combination may cause durable remission. Patients with durable remission have significantly lower organ damage.

Effects of melatonin supplementation on serum oxidative stress markers and disease activity in systemic lupus erythematosus patients: A randomised, double-blind, placebo-controlled trial.

BACKGROUND: Considering pathological significance of oxidative stress in systemic lupus erythematosus (SLE), current research aimed to evaluate the effects of melatonin supplementation on oxidative stress markers and disease activity in SLE. METHOD: In this randomised double-blind, placebo-controlled trial, 32 SLE females were selected and randomly assigned into two groups to take 10 mg/day melatonin or placebo for 12 weeks. Before and after trial, serum malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured and disease activity was determined by Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K). RESULTS: Twenty-five patients (13 in the melatonin and 12 in the placebo groups) completed the trial. Melatonin supplementation caused significant reduction in serum MDA compared with baseline (P = .003) and placebo group (P = .004). Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group (P > .05). Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group (P > .05). CONCLUSION: This study demonstrated affirmative effects of melatonin in decreasing oxidative stress in SLE patients without any effect on disease activity. Further investigations are required to affirm these primitive findings and to achieve concise conclusions.What's known Free radical damage and oxidative stress has a remarkable function in systemic lupus erythematosus (SLE) pathogenesis. Products derived from oxidative modification cascades are found in biological fluids and their redundancy has a correlation with disease activity and organ damage in SLE. Dietary supplements, which decrease oxidative stress, would be useful in managing SLE. Melatonin is a potent antioxidant and has anti-inflammatory and immunomodulatory characteristics. Limited in vitro and animal studies are available indicating desirable effects of melatonin in preventing from SLE organ damage, thereby opening a new area of investigation that can contribute to using melatonin as a therapy or co-therapy for SLE. What's new Melatonin supplementation caused significant reduction in serum MDA compared with baseline and placebo group. Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group. Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group.

Long-term outcome and predictors of remission in Behçet's disease in daily practice.

BACKGROUND: Many factors can influence the response to treatment and prognosis of Behçet's disease (BD). Identifying the predictors of response to treatment can improve the quality and decrease the cost of medical care. This analytical study was performed to identify factors affecting the remission and outcome in BD patients with long-term follow-up. METHODS: A total of 245 BD patients aged over 16 years were followed for at least 12 months and visited at least three times a year were included. The outcome was assessed by the number of patients who were in sustained and long-term remission, had lost the primary criteria of BD for at least 12 months, were asymptomatic, and developed the sequela of disease or deceased. Sustained remission was defined as being in remission for at least six months. Long-term remission was defined as remission for ≥ 5 years. RESULTS: Mean age and mean duration of follow-up were 35.1 ± 10.7 years and 92.3 months, respectively. At the end of follow-up, 63.2% of the patients lost the criteria of BD, 51.8% of the cases were in sustained remission, and 36.2% of them were asymptomatic. Predictors of sustained remission were adherence to therapy and treatment for more than six years. Having genital ulcers and treatment with methotrexate were associated with non-remission. Predictor of long-term remission was remission induction in the first two years of the treatment. Treatment with methotrexate was associated with non-remission. Poor outcome was observed in 31.8% of patients. Male sex, obesity, and having severe disease were the risk factors of poor outcome. CONCLUSION: Achieving remission in BD is not inaccessible. Treatment with conventional and biologic disease-modifying antirheumatic drugs may cause sustained and long-term remission. Adherence to treatment, remission induction during the two years after the diagnosis and treatment for at least six years have significant role.

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. METHODS: Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR-27, miR-17, and miR-146a) and cytokines including Interleukin-10 (IL-10), TGF-ß, and IL-6 were assessed by real-time polymerase chain reaction. Furthermore, enzyme-linked immunosorbent assay was done to determine the secretion levels of cytokines. RESULTS: After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT-PCR data indicated that the expression of miR-17 and miR-27 were significantly decreased following nanocurcumin treatment while miR-146a and FoxP3 were significantly increased. Moreover, nanocurcumin-treated group had high levels of IL-10 and TGF-ß and low levels of IL-6 production than control group. CONCLUSION: The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

Clinical characteristics and long-term outcome of Takayasu arteritis in Iran: a multicentre study

Background/aim: This study aimed to evaluate the demographic, clinical, angiographic and prognostic characteristics of Takayasu arteritis (TA) in Iran. Materials and methods: A total of 75 patients with TA based on the American College of Rheumatology 1990 criteria for TA classification referred to the Rheumatology Centres, were followed-up from 1989 to 2019. Demographic, clinical, angiographic and prognostic characteristics were collected at baseline and last visit. Results: The mean age was 31.9 ± 9.8 years at the disease onset. Female to male ratio was 14. The median latency in diagnosis was 24 months. Pulse discrepancy in the arms, blood pressure discrepancy in the arms, limb claudication, hypertension and constitutional symptoms were the most common clinical features. The most common angiographic type at the time of diagnosis was Type I (42.7%). The most frequent arterial lesion was stenosis (89.4%). Subclavian, carotid and aortic arteries were the most commonly involved arteries. New lesions developed in 28.6% of patients during the 5.25-year follow-up. Vasculitis-induced chronic damage was observed in all patients. Disease activity decreased and vascular damage remained stable throughout the follow-up period. Conclusions: The clinical features and angiographic type of TA in Iran are different from most Asian countries. Differences in angiographic and clinical features may lead to delayed diagnosis. The issue of delay in diagnosis should create awareness among health care providers that TA is not a very rare disease in Iranians and failure to pay attention to warning symptoms may delay the diagnosis.

Nanocurcumin: A novel strategy in treating ankylosing spondylitis by modulating Th17 cells frequency and function.

Ankylosing spondylitis (AS) is a chronic rheumatic disease which mainly affects the axial skeleton and sacroiliac joints. T-helper 17 (Th17) cells have been reportedly involved in AS pathogenesis. Nanocurcumin is considered to be beneficial, as an anti-inflammatory compound, in AS patients treatment. In this study, Th17-related immunological parameters were evaluated in AS patients. Transcription factors messenger RNA (mRNA) expression level, cytokines, and related microRNAs (miRNAs) were measured by real-time polymerase chain reaction. Additionally, Th17 frequency and cytokines secretion were evaluated by flow cytometry and enzyme-linked immunosorbent assay tests, respectively. The frequency of Th17 was higher in AS patients. Gained data from nanocurcumin group also demonstrated that retinoic acid-related orphan receptor γ (RORγt) and interleukin-17 (IL-17) mRNA expression levels were significantly decreased (P = 0.0001 and 0.0006, respectively), as the decrease also happened in Th17-associated miRNAs including miR-141, miR-155, and miR-200 ( P = 0.04, P = 0.02, and P < 0.0001, respectively). Posttreatment data of miR-155 and miR-200 in the nanocurcumin and placebo groups also showed a higher expression level in the placebo group compared with nanocurcumin-treated patients. Some clinical symptoms of AS patients were also improved at the end of the treatment process. The results of this study showed the potential ability of nanocurcumin to regulate Th17 cells activity in AS patients. This study provided further evidence on the function and underlying mechanism of nanocurcumin helping better treatment of AS.

Low dose cyclosporine A in the treatment of resistant proliferative lupus nephritis.

OBJECTIVE: This study aimed to evaluate long-term efficacy of low dose cyclosporine A (CsA) in the treatment of resistant proliferative lupus nephritis. METHODS: In this retrospective study, patients with biopsy proven proliferative lupus nephritis who were unresponsive to combination therapy with steroid plus mycophenolate mofetil (MMF) or cyclophosphamide (CYC) and had been treated with CsA were included. Efficacy monitoring was based on the systemic lupus erythematosus (SLE) disease activity index, dose of prednisolone, serum complement, anti-double stranded DNA (anti-dsDNA) titration, urine analysis, proteinuria, creatinine clearance, remission of the renal disease, renal survival and involvement of other organs. RESULTS: This study included 27 consecutive patients (22 females, 5 males) with resistant proliferative lupus nephritis. Mean duration of follow up and treatment with CsA were 40.7 ± 24.9 and 35.2 ± 19.1 months, respectively. Complete and partial renal remission occurred in 66.9% and 25.7% patients, respectively. Creatinine clearance was stable, proteinuria and anti-dsDNA titer decreased, and C3 and C4 increased significantly during the treatment with CsA. Severe complications such as death, dialysis, kidney transplantation and severe infection did not occur in the studied patients during the follow-up period. CONCLUSIONS: Low-dose CsA could induce renal remission and ameliorate the SLE disease activity in patients with resistant proliferative lupus nephritis and it would be a safe drug for treatment of these patients.

Endothelin-1, α-Klotho, 25(OH) Vit D levels and severity of disease in scleroderma patients.

Considering the role of endothelin-1 (ET-1) in tissue remodeling and fibrosis during the development of scleroderma as well as the effect of α-Klotho in pathogenesis of calcinosis and/or endothelial cell injury and its correlation with severity of disease, this study aimed to evaluate serum ET-1, α-Klotho and 25(OH) vitamin D levels in patients with limited and diffuse scleroderma compared to healthy subjects. In this cross-sectional study, 60 scleroderma patients according to the ACR/EULAR 2013 criteria and 60 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and Medsger severity scale was assessed. Serum ET-1, soluble α-Klotho and 25(OH)D3 levels were measured using ELISA kits. The mean ± SD age of patients and controls was 46.2 ± 9.6 and 47.2 ± 7.0 years, respectively. Compared to healthy controls, serum ET-1 was significantly higher in SSc patients (p = 0.001); whilst serum α-Klotho and 25(OH)D3 were significantly lower in patients (p = 0.001). The most common organs involved in patients were skin, lung, peripheral vascular and gastrointestinal system and the severity of involvement was mainly mild and/or moderate. There were no significant differences in serum ET-1 and α-Klotho levels according to the severity of different organ involvement (p > 0.05). There was no significant correlation between presence or absence of calcinosis and negative or positivity of auto-antibodies with ET-1, α-Klotho and 25(OH)D3 levels. Although our study revealed higher serum ET-1 and lower serum α-Klotho levels in SSc patients compared to healthy controls, there were not any significant correlations between their serum levels with severity of organ involvement.

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA. MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention. RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05). CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.

Adalimumab-induced leukocytoclastic vasculitis in a patient with ankylosing spondylitis: A case report.

Clinical Key Message: In patients receiving anti-TNF-α drugs for ankylosing spondylitis, monitoring purpuric and ischemic skin lesions is crucial. This case underscores the significance of identifying and addressing drug-induced vasculitis while stressing the necessity for prompt evaluation and exploration of alternative treatment options to safeguard patient well-being. Abstract: The case discusses a 38-year-old female with a history of ankylosing spondylitis (AS) who presented with skin lesions, including purpuric skin lesions and ischemia of her right foot digits, after initiating treatment with adalimumab. After excluding other potential causes, such as infections and malignancies, the patient received a diagnosis of moderate-sized vascular vasculitis associated with adalimumab use. Discontinuation of adalimumab and treatment with high dose glucocorticoids and intravenous pulse of cyclophosphamide resulted in the resolution of her ischemic lesions. This case underscores the importance of considering drug-related side effects in patients with new skin lesions, particularly in the context of rheumatic diseases such as AS.

Predictors of medications-free and long-term remission in anti-neutrophil cytoplasmic antibody-associated vasculitis: Real-world evidence.

BACKGROUND AND AIM: In this study, we report the outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in daily practice based on Connective Tissue Diseases Research Center-Vasculitis Registry (CTDRC-VR) data. METHODS: Patients were included if they were 18 years or older, had a diagnosis of the groups of AAV based on 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis, and were followed for a period longer than 2 years or were died. Complete clinical remission was defined as granulomatosis with polyangiitis (BVAS/GPA) of 0. Sustained remission was defined as a complete clinical remission for at least six months and tapering prednisolone dose to ≤ 7.5 mg/d. Long-term remission was defined as complete clinical remission for ≥ 5 years and tapering prednisolone dose to ≤ 7.5 mg/d. Medications-free remission was defined as complete clinical remission and discontinuation of glucocorticoids, cytotoxic medications and biologics. RESULTS: Sixty patients with AAV were enrolled in this study. Sustained and long-term remission were developed in 91.7 and 72.1 percent of patients, respectively. Relapse was developed in 27 (45%) patients. Medications-free remission was developed in 23 (33.3%) patients. Vasculitis induced damage was developed in 40 (66.7%) patients. Patients with damage had significantly lower age and higher BVAS at the baseline. Upper airway and renal involvement, and non-adherence in patients with damage was significantly more common. CONCLUSIONS: Induction therapy leads to long-term and medications-free remission in 72% and 38% of patients with AAV, respectively.

A multicenter study of long-term outcomes of relapsing polychondritis in Iran.

Relapsing polychondritis (RP) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas. RP may cause extensive tissue destruction and is associated with significant morbidity and mortality. In this multicenter study, we considered the remission status and long-term outcomes of RP in patients who were followed-up in six referral rheumatology centers in Iran. Outcomes of disease was assessed by remission status and RP induced damage. A total of 29 patients with RP were examined for enrollment in the study, and 26 patients with a minimum follow-up period of 6 months were included in the RP outcome analysis. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively. Prednisolone was discontinued in 8 (30.8%) patients and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing-remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RP induced damage was developed in 21 (80.8%) patients. Ear deformity and osteoporosis were the most common RP induced damage. Long-term remission and medications-free remission in RP is accessible. However, RP related damage occur in majority of patients.

Serum salusin-ß levels in patients with systemic lupus erythematosus.

OBJECTIVE: Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-ß with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-ß levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement. METHODS: In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit. RESULTS: Serum salusin-ß levels in SLE and control groups were 474.2 ± 117.1 pg/ml and 157.7 ± 88.7 pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-ß levels with age (r = - 0.06, P = 0.632) and SLEDAI (r = - 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-ß was significantly higher. In addition, in patients with serositis, serum salusin-ß was significantly lower. Multiple linear regression analysis showed that serum salusin-ß levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. CONCLUSIONS: Our findings showed that salusin-ß might have a possible role in the pathogenesis of SLE. Salusin-ß may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-ß levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-ß levels with age and SLEDAI. • Serum salusin-ß levels retained a significant association with nephritis and thrombosis.

Prevalence and predictors of long-term remission in rheumatoid arthritis in real-world practice: a longitudinal study.

OBJECTIVES: The aim of the present study was to provide real-world evidence for factors predicting long-term remission in a longitudinal study of rheumatoid arthritis (RA) patients. METHODS: Long-term remission was defined by meeting American Rheumatism Association (ARA) criteria for remission and prednisolone dose ≤ 5 mg/d for at least 5 years. Patients in this cohort were treated by tight control strategy using step-up combination therapy with conventional synthetic DMARDs (csDMARDs), biologic DMARDs. The parameters associated with long-term remission were subjected to univariate analysis, and parameters with P-values of < 0.1 in univariate analysis were included in a multivariate regression analysis. RESULTS: One thousand two hundred and eighty-six RA subjects were considered for eligibility, and finally, 499 patients were included in the study. Median duration of follow-up was 108 months. Long-term remission occurred in 157 (31.5%) patients. Median time to long-term remission was 8 (5, 41) months. Predictors of long-term remission were absence of flare during the course of disease, occurrence of sustained remission during 6 months after starting therapy, age at the disease onset > 60, being anti-citrullinated protein antibodies (ACPA) negative, and Disease Activity Score-28 (DAS28) at cohort entry ≤ 5.1. CONCLUSION: In real-world practice, long-term remission occurs in 31.5% of patients treated with a tight control strategy. Absence of flare during the course of disease, occurrence of sustained remission during 6 months after starting therapy, age at the disease onset > 60, being ACPA negative, and DAS28 at baseline ≤ 5.1 are independent predictors of long-term remission. Key Points • In real-world practice, long-term remission occurs in 31.5% of patients treated with a tight control strategy. • Median time to long-term remission was 8 months. • Absence of flare during the course of disease, occurrence of sustained remission during 6 months after starting therapy, age at the disease onset >60, being ACPA negative, and DAS28 at baseline ≤ 5.1 are independent predictors of long-term remission.

Clinical course, chest computed tomography severity score and outcome of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases.

Aim of the work: To assess the clinical manifestations, imaging findings and outcomes of corona virus disease 2019 (COVID-19) in patients with rheumatic diseases. Patients and methods: In a three-center study, patients with rheumatic diseases who developed COVID-19 were included. Patients were classified into two groups, i) inflammatory arthritis including rheumatoid arthritis (RA), spondyloarthritis (SpA) and undifferentiated arthritis, ii) connective tissue diseases (CTDs) including systemic lupus erythematosus (SLE), vasculitis and others. COVID-19 outcomes were assessed based on chest computed tomography severity score (CT-ss), the level of care, the number of patients who died and flare of underlying rheumatic disease. Results: One hundred ninety-six patients with a mean age of 47.9 ± 15.1 years, 73.5% female, were included. Underlying rheumatic diseases were RA (57.7%), SLE and other CTDs (17.9%), SpA (11.2%), vasculitis (11.2%) and undifferentiated arthritis (2%). Myalgia, malaise and fever were the most common clinical manifestations of COVID-19. Pneumonia on computerized tomography (CT), hospitalization, admission in intensive care unit and need to mechanical ventilation were observed in 75.5, 37.2%, 10.7% and 6.6% of patients, respectively. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, diabetes and underlying pulmonary disease were predictors of moderate to severe pneumonia and hospitalization. Fifteen (7.6%) patients died. Flare of underlying rheumatic disease occurred in 16.3% of patients. Flare of disease in patients with CTDs was significantly more than other rheumatic diseases. Conclusions: In rheumatic patients, treatment with NSAIDs or prednisolone, diabetes and pulmonary disease are risk factors of moderate to high CT-ss and hospitalization during COVID-19.

Survivin; a novel therapeutic target that correlates with survival of autoreactive T lymphocytes obtained from patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is progressive immune-mediated arthritis. Persistent autoreactivity of T cells with an up-regulated Survivin expression is strongly implicated in AS immunopathogenesis. Besides, Survivin can inhibit proapoptotic caspase 9 activations. Moreover, microRNAs are small non-coding RNAs that are dysregulated in various diseases, in which their altered expression could modulate Survivin expression. The primary goal of this study was to assess the role of Survivin and its-targeting microRNAs in the immunopathogenesis of AS disease. For this aim, peripheral blood mononuclear cells (PBMCs) were isolated from 15 patients with AS and healthy matched controls using Ficoll-Hypaque. T cells were obtained using the magnetic-activated cell sorting (MACS) method. After that, the expression levels of Survivin, Caspase 9, and specific miRNAs were determined using qT-qPCR. Also, the expression of Survivin and Caspase 9 at protein levels was determined by western blotting. Then, the isolated T cells were co-cultured with interleukin (IL)-2 and muromonab-CD3 (OKT-3) for active-induced cell death (AICD) induction, Survivin siRNA for inhibition of Survivin expression, and their combination to assess the implication of Survivin expression in autoreactive T lymphocytes' resistance to apoptosis by determining the rate of apoptosis by Flowcytometry assay. The results showed that Survivin was up-regulated while Caspase 9 was downregulated in patients with AS. It was also revealed that microRNAs that directly or indirectly target the Survivin mRNA were dysregulated in patients with AS. It was also revealed that T cells obtained from AS patients were more resistant to apoptosis induction than those obtained from healthy people. In summary, the results obtained from this study showed that dysregulation of Survivin and Survivin-targeting miRNAs in T lymphocytes obtained from AS patients contribute to their resistance to apoptosis, suggesting the future development of targeted therapies for AS.

The effect of osteoporotic and non-osteoporotic individuals' T cell-derived exosomes on osteoblast cells' bone remodeling related genes expression and alkaline phosphatase activity.

OBJECTIVES: Osteoporosis is a common skeletal disorder attributed to age and is defined as a systematic degradation of bone mass and the microarchitecture leading to bone fractures. Exosomes have been reported in almost all biological fluids and during the failure of bone remodeling. 20 ml of blood samples were obtained from osteoporotic and non-osteoporotic postmenopausal women. After the isolation of peripheral blood mononuclear cells (PBMCs), T cells were separated via the magnetic-activated cell sorting (MACS) technique. Exosomes were driven from T cells of non-osteoporotic and osteoporotic volunteers. Subsequently, normal osteoblasts were treated with obtained T cell exosomes to assess osteoblastic function and gene expression. RESULTS: Runx2, type I collagen, osteopontin, and osteocalcin expression decreased in osteoblasts treated by osteoporotic T cell exosomes. In contrast, an increased expression of the mentioned genes was observed following non-osteoporotic T cell exosome treatment. Additionally, osteoblast alkaline phosphatase (ALP) activity treated with non-osteoporotic T cell exosomes increased. However, this activity decreased in another group. Our data demonstrated that T cell exosomes obtained from osteoporotic and non-osteoporotic individuals could alter the osteoblastic function and gene expression by affecting the genes essential for bone remodeling.