The Role of Tenascin-C in the Physiopathology of Familial Mediterranean Fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autoinflammatory disease common in the Mediterranean basin. It has been determined that tenascin-C level is increased in rheumatic inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus, and systemic sclerosis. However, the role of tenascin-C has not been investigated in FMF. This study aimed to investigate serum tenascin-C levels in FMF patients and to investigate possible relationships between them. MATERIALS AND METHODS: About 38 patients diagnosed with FMF and 40 healthy controls were included in the study. The patient's sex, age, clinical symptoms, physical examination, and laboratory results were recorded. Serum tenascin-C levels were determined by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The serum tenascin-C levels were significantly lower in the FMF patients (10297 ± 8107 pg/ml) compared to the healthy control group (29461 ± 13252 pg/ml) (p < 0.001). In receiver operating characteristic (ROC) analysis, when the cut-off point was chosen as 11076 pg/ml, sensitivity was 77.1% and specificity was 91.9%. When the cut-off point was chosen as 19974 pg/ml, sensitivity was 91.4% and specificity was 75.7%. It was determined that the serum tenascin-C levels did not correlate with age, gender, and laboratory parameters in the healthy control group and FMF patients (p > 0.05). CONCLUSION: This is the first study investigating tenascin-C levels in FMF. Tenascin-C levels in FMF patients were lower than in healthy controls. Low tenascin-C levels in FMF, which are high in other chronic rheumatic diseases, may be a valuable indicator. Therefore, serum tenascin-C level seems to be a useful marker in distinguishing FMF patients from healthy individuals.

An investigation of the relationship between Behçet's disease and tenascin-C.

Objectives: The study aimed to investigate serum tenascin-C levels and its relationship with pathogenesis of Behçet's disease (BD) with inflammatory processes. Patients and methods: This prospective and analytical study included 34 BD patients (19 males, 15 females; mean age: 31.5±8.2 years; range, 18 to 48 years) who met the 2014 International Criteria for Behçet's Disease and had no comorbidities and 37 healthy volunteers (21 females, 16 males; mean age: 29.6±5.3 years; range, 21 to 45 years). Sex, age, age at diagnosis, clinical and laboratory data, medication use, and smoking history of the participants were recorded. Serum tenascin-C levels were measured using a commercially available tenascin-C enzyme-linked immunosorbent assay kit. Results: There was no significant difference between the groups in terms of age (p=0.262) and sex (p=0.287). Serum tenascin-C levels were significantly lower in the BD group (10,824±7,612 pg/mL) compared to the control group (27,574±14,533 pg/mL, p<0.001). In the receiver operating characteristic analysis performed for the diagnostic value of tenascin-C level in BD, the sensitivity was determined as 79.4% and the specificity as 82.5% (p<0.001). No statistically significant difference was observed in tenascin-C levels in correlation with clinical characteristics, laboratory values, medication use, and smoking in the BD group. Conclusion: In contrast to other chronic inflammatory diseases, lower levels of tenascin-C were observed in patients with BD than in the healthy individuals, which can be attributed to the absence of prolonged chronic inflammatory course in BD. The fact that tenascin-C levels are high in other rheumatic inflammatory diseases but low in BD may be useful in the differential diagnosis of BD.

The Relationship Between COVID-19 Disease Severity and Zonulin Levels.

Introduction Zonulin is a protein that plays a role in the reversible regulation of epithelial permeability. As zonulin is released in large amounts into the intestinal lumen, it disrupts the integrity of the tight junctions and causes continuous migration of antigens to the submucosa. Consequently, it can trigger inflammatory processes and severe immune reactions. In severe cases, SARS-CoV-2 may have a major impact on the clinical manifestations of the disease by directly or indirectly affecting intestinal cells and triggering systemic inflammation. Therefore, our study aimed to investigate the role of one of the possible mediators, zonulin, in the severity of the COVID-19 infection. Methods  Thirty COVID-19 patients and 35 healthy controls were included in the study. Blood samples were taken from the patients on the 1st, 4th, and 8th days of hospitalization. Serum zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood count (white blood cell [WBC], neutrophil, lymphocyte, and platelet), biochemical parameters (serum lactic acid dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], D-dimer, ferritin, fibrinogen levels) were determined and chronic systemic disease states of the patients were assessed. Results  Serum zonulin levels were notably higher in the healthy control group compared to the patient group (p=0.003). Although there was an increase in the zonulin values by time in hospitalization, this rising was not significant. Conversely, ESR and CRP levels were significantly higher in the patient group (p<0.001). There was no significant difference between the two groups regarding gender, age, and WBC counts. Conclusion  The serum zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum zonulin levels were not correlated with ESR, CRP, and other inflammation markers. Our results suggest that low serum zonulin levels in COVID-19 patients might represent a mild disease course.

Ovarian Reserve and Pelvic Ultrasound Assessment in Familial Mediterranean Fever.

Introduction Familial Mediterranean fever (FMF) is an inflammatory rheumatic disease that affects people in their reproductive period. The aim of this study was to investigate the number of gravida, ovarian reserve, and ovarian doppler characteristics in FMF patients. Methods The study design is cross-sectional. Between November 1, 2018, and October 31, 2019, 40 FMF patients, and 40 age-matched volunteers were included in the study. Early follicular phase follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progesterone, and anti-Mullerian hormone (AMH) levels, as well as ovarian volume, antral follicle count (AFC), ovarian stromal artery doppler findings, and pelvic pathologies, were evaluated. Results The number of gravida, and the AFC was significantly higher in the control group (16.00 ± 5.22) compared to the patients with FMF (13.00 ± 4.09) (p = 0.026). LH values were significantly higher in the FMF group. Thirteen patients (32.5%) received anakinra and colchicine, and 27 patients (67.5%) received only colchicine. There was no significant difference between the patients receiving anakinra, and the patients receiving colchicine in terms of AMH, FSH, AFC, and E2 values. Conclusion FMF patients were found to have low gravida and AFC, and a significant portion was observed to have pelvic fluid and hydrosalpinx. In conclusion, the presence of pelvic fluid, hydrosalpinx, and low AFC persist in FMF patients despite colchicine and/or anti-interleukin-1 treatments. The low gravida may be related to these pathologies detected in patients with FMF.

Infliximab therapy in parenchymal neuro-Behçet's disease: A single-center experience.

BACKGROUND: Parenchymal neuro-Behçet's disease involvement is the most serious complication of Behçet's disease, and no sufficient data on its treatment exists. This study aims to investigate the efficacy and safety of infliximab treatment in neuro-Behçet's disease patients with parenchymal involvement. MATERIALS AND METHODS: Patients who were diagnosed with Behçet's disease with parenchymal neurological involvement and underwent infliximab treatment for at least 12 months were included in the study. Demographic, clinical, and radiological data of the patients were accessed through the electronic database of our hospital. RESULTS: This study comprises 19 patients who were diagnosed with neuro-Behçet's disease and used infliximab: 12 male and 7 female patients. The mean age of the patients was 36.5 ± 11.7 years, and the diagnostic age was 26.3 ± 10.8 years. The duration of treatment with infliximab was 32.3 months (minimum 11, max 79). In the 19 patients receiving infliximab treatment, 11 (58%) patients achieved remission (complete disappearance of neurological symptoms) and 7 (37%) patients achieved disease stability (no new neurological findings); steroid treatments were discontinued for these 18 patients. In addition, only 5 patients were concomitantly taking immunosuppressive drugs with the infliximab. Infliximab was discontinued after the development of a new parenchymal attack in the 9th month of infliximab treatment. CONCLUSION: In conclusion, parenchymal neurological involvement in Behçet's disease is an important cause of disability, and no sufficient data exists in literature on its treatment. The results of our study suggest that infliximab treatment was effective and safe in neuro-Behçet's disease parenchymal involvement for preventing long-term neurological attacks and discontinuing corticosteroid treatment.

The inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathways

Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings. Materials and methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP ­1, ­3, and ­13 levels in FLSs culture were determined by ELISA. Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP ­1, ­3, and ­13 expressions from FLSs induced by IL-1ß and TNF-α were increased, while dasatinib suppressed their productions from FLSs. Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA.

Clinical manifestations of Behçet's syndrome: A single-center cohort of 777 patients.

OBJECTIVE: Behçet's syndrome (BS) is a multisystem variable vessel vasculitis characterized by skin-mucosal lesions. It can also involve the eyes, blood vessels, joints, gastrointestinal system, urogenital system, and central nervous system. BS starts in the third or fourth decade and affects both genders equally. The disease is more severe in young men. Although the sensitivity of the pathergy test (PT) is decreasing today, it is still an important clue in the diagnosis of BS. We describe the characteristics of BS in our region, retrospectively. We also analyzed the effect of gender, age, family history, and skin PT positivity status on the difference of clinical involvement. METHODS: A total of 777 BS patients (391 women and 386 men; 40.0 ± 11.6 years old) who applied to our Rheumatology Department between January 2010 and June 2020 were included in the study. RESULTS: Of the 777 patients, 391 were female (50.3%) and 386 were male (49.7%). The mean age at diagnosis was 30.3 ± 9.8 years. The proportion of patients with BS in their family was 10.2%. Of the 777 patients, 310 (39.9%) had only mucocutaneous symptoms. Other 467 patients (60.1%) had at least one of the ocular, musculoskeletal, vascular, neurologic, intestinal, or genitourinary involvement. Serious involvements such as eye, cardiovascular, and neurologic involvement were more common in male patients. CONCLUSION: BS has the different clinical phenotypes according to gender, age of onset, and skin PT positivity status. Gender influences on the major organ involvements such as eye, neurologic, and vascular.

The receptor for advanced glycation end product (RAGE) pathway in COVID-19.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) with lung involvement frequently causes morbidity and mortality. Advanced age appears to be the most important risk factor. The receptor for advanced glycation end-product (RAGE) pathway is considered to play important roles in the physiological aging and pathogenesis of lung diseases. This study aimed to investigate the possible relationship between COVID-19 and RAGE pathway. MATERIALS AND METHODS: This study included 23 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed tomography. Serum soluble-RAGE (sRAGE) levels were determined using enzyme-linked immunosorbent assay. RESULTS: The sRAGE levels were significantly higher in the asymptomatic group than in the control group. Age, fibrinogen, C-reactive protein, and ferritin levels were higher and the sRAGE level was lower in the patients with lung involvement than in the asymptomatic patients. CONCLUSIONS: In this study, patients with high sRAGE levels were younger and had asymptomatic COVID-19. Patients with low sRAGE levels were elderly patients with lung involvement, which indicates that the RAGE pathway plays an important role in the aggravation of COVID-19.

The assessment of the serum levels of TWEAK and prostaglandin F2α in COVID ­ 19

Background/aim: It is claimed that aberrant immune response has a more important role than the cytopathic effect of the virus in the morbidity and mortality of the coronavirus disease 2019 (COVID-19). We aimed to investigate the possible roles of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 pathway and leukotrienes (LT) in uncontrolled immune response that occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Materials and methods: This study included 25 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed-tomography. Serum TWEAK, LTE4, and prostaglandin F2α (PGF2α) levels were determined. Results: Compared with the healthy control group, TWEAK, LTE4, and PGF2α levels were higher in the group of SARS-CoV-2 infection without lung involvement. In the group of SARS-CoV-2 infection with lung involvement, age, fibrinogen, sedimentation, C-reactive protein and ferritin, TWEAK, LTE4, and PGF2α levels were higher, and lymphocyte levels were lower compared with the asymptomatic group. Conclusions: In the study, TWEAK and LTE4 levels increased in cases with COVID-19. These results support that TWEAK/Fn14 pathway and LT may involved in the pathology of aberrant immune response against SARS-CoV-2. Inhibition of each of these pathways may be a potential target in the treatment of COVID-19.