Rapamycin Improves Vascular Remodelling in a Controlled Rat Model of Monocrotaline-Induced Pulmonary Hypertension

ABSTRACT Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by the progressive elevation of the pulmonary arterial resistance, leading to the right ventricular failure and death. Objective: To evaluate the effect of rapamycin (RAPA), a potent cell-cycle inhibitor, on exercise capacity, right ventricular hypertrophy and pulmonary vascular remodelling on rats. Methods: A total of 39 nine-week-old male Wistar rats (160-240 g) were divided into three groups: the control (n = 10), PAH control (n = 15) and PAH-RAPA (n = 14) groups. On the 1st day, 60 mg/kg monocrotaline was injected intraperitoneally to induce PAH in the PAH control group and PAH-RAPA groups. On the 21st day, 3 mg/kg/day RAPA was started orally, and the animals were followed for 35 days. On the 35th day, the exercise capacity of the rats was analysed through a modified forced swimming test. After measuring their right ventricular systolic pressure using an open-chest method, their hearts and lungs were excised and analysed histopathologically for right ventricular hypertrophy and pulmonary vascular remodelling. Results: Rapamycin treatment provided limited and insignificant improvements in exercise capacity, right ventricular systolic pressure and right ventricular hypertrophy of the rats. However, there was significant recovery in the rats' pulmonary artery muscular layer thickness with the RAPA treatment (p < 0.049). On the 35th day, the mortality rate was 0% in the control group, 53.1% in the PAH control group and 42.9% in the PAH-RAPA group. No statistically significant decrease was observed in their mortality rates with the RAPA treatment (p > 0.16); however, a significant recovery was noted in terms of the rats' median life span (p < 0.006). Conclusion: Pulmonary artificial hypertension is a progressive disease that is not curable with current therapies. Rapamycin may have the potential to reverse vascular remodelling and prolong life expectancy in cases of pulmonary hypertension.

Relationship among egg quality traits in Japanese quails and prediction of egg weight and color using data mining algorithms.

The present paper aims to predict egg weight from some egg quality characteristics (egg weight, yolk weight, albumen weight, shell thickness, shell weight, shape index, albumen index, yolk index, yolk scale, and Haugh unit) in Japanese quails and to classify 94 eggs collected in regards to their shell colors. In the present study, CART and MARS data mining algorithms were assessed in the prediction of egg weight of the quails with the content of detecting egg quality standards of the studied quail genotypes for breeding and marketing strategies. In the classification of the collected quail eggs on their shell colors, classification performances of CART, CHAID, exhaustive CHAID, and QUEST algorithms were measured. Among those, CART was selected as the best classification algorithm according to eggshell color. The highest significant correlations were obtained for egg weight-yolk weight (0.740) and egg weight-albumen weight (0.735), respectively, in considering egg internal and external quality traits in quails. CART algorithm more accurately classified all eggshell colors compared with other algorithms. MARS showed much better predictive performance than CART that produced 0.850 Rsq and 0.728 cross-validation Rsq for prediction of egg weight in quails. In conclusion, the obtained results revealed that data mining algorithms may be useful references in practice for quail breeders in the development of new selection strategies and characterization of the studied animal materials.

Results of Real-time Multiplex Polymerase Chain Reaction Assay in Renal Transplant Recipients With Sterile Pyuria.

Urinary tract infections are a major cause of morbidity and hospitalization after renal transplantation. Patients treated with immunosuppressive drugs suffer not only from common uropathogens but also from opportunistic infections caused by unusual uropathogens. Sterile pyuria is associated with numerous infectious agents including viruses, fungi, and atypical or fastidious organisms. The objective of this study was to investigate the pathogens using real-time multiplex polymerase chain reaction (rtMPCR) assay in sterile pyuria of renal transplant recipients. In this prospective controlled study, pathogen detection was performed with rtMPCR assay on October 2016 in 60 patients with sterile pyuria who had undergone kidney transplantation. A total of 40 renal transplant patients were determined as the control group. Male-to-female ratio was same. The mean age of the subjects with sterile pyuria was 45.7 ± 12.1 (25-74). The mean duration after transplantation was 28.8 ± 3.97 (3-102) months. Pathogens were detected with rtMPCR in 61.7% of sterile pyuria group. This rate was significantly higher compared with the control group (P < .001). Two or more different pathogens were found in 13 (21.7%) patients in sterile pyuria group. The pathogens found included cytomegalovirus in 10 patients (19%), Gardnerella vaginalis and obligate anaerobes in 20 patients (38%), Ureaplasma spp in 17 patients (33%), Candida spp in 2 patients (4%), Mycoplasma hominis in one patient (2%), herpes simplex virus-2 in one patient (2%), and Trichomonas vaginalis in one patient (2%). Sterile pyuria may indicate the presence of genitourinary pathogens that cannot be detected with conventional urine culture method in renal transplantation patients. rtMPCR is an accurate and convenient method for detection of multiple potential pathogens of sterile pyuria in renal transplant patients.

Short-term effects of intravitreal ranibizumab and bevacizumab administration on 24-h ambulatory blood pressure monitoring recordings in normotensive patients with age-related macular degeneration.

PurposeTo evaluate effects of intravitreal ranibizumab and bevacizumab administration on ambulatory blood pressure monitoring (ABPM) recordings in normotensive patients with age-related macular degeneration (AMD).Patients and methodsA total of 72 patients (mean age: 61.8(6.2) years, 52.8% were females) diagnosed with AMD were included in this study as divided into ranibizumab (n=34) and bevacizumab (n=38) treatment groups. Twenty-four hour, nighttime, and daytime ABMP values for systolic and diastolic BP were recorded in study groups before and after the third intravitreal injection of ranibizumab or bevacizumab.ResultsRanibizumab injection had no impact on ABPM recordings and dipping status. In the bevacizumab group, increased daytime (129.0(6.6) vs 127.7(6.6) mm Hg, P=0.002) and nighttime systolic (116.9(7.5) vs 112.6(7.1) mmHg, p<0.001) BP and decreased daytime diastolic (80.1(6.5) vs 82.4(6.1)mm Hg, P=0.001) BP were noted in the post-injection period. Also, percentage of non-dippers was significantly increased from 5.3% at pre-injection to 28.9% (P=0.004) at the post-injection period.ConclusionIn conclusion, given that it has no significant impact on ABPM recordings and dipping status, in our study, intravitreal ranibizumab injection may be the better choice in the management of AMD.

First International Paired Exchange Kidney Transplantations of Turkey.

OBJECTIVE: We estimated that many patients on the waiting list for kidney transplantation in Turkey have immunologicaly incompatible suitable living donors. Paired exchange kidney transplantation (PETx) is superior to desensitization for patients with incompatible donors. Recently we decided to begin an international PETx program. METHODS: We report three international living related paired kidney transplantations which occurred between May 14,2013, and March 7, 2014. The international donor and recipient operations were performed at Medical Park Hospital, Antalya, Turkey. All pairs were living related and written proofs were obtained according to Turkish laws. As with the donor procedures, the transplantation procedures were performed at the same time. RESULTS: The uniqueness of these transplantations was that they are the first international exchange kidney transplantations between Turkey and Kirghizia. Currently all recipients are alive with wel-functioning grafts. CONCLUSION: In our institute, a 5% increase was obtained in living-related kidney transplantations by the help of PETx on a national basis. We believe that international PETx may also have the potential to expand the donor pool.

Post-transplantation Malignancy After Kidney Transplantation in Turkey.

OBJECTIVE: Kidney transplantation is the best treatment option for end-stage renal disease patients. Increased incidence of post-transplantation malignancy can be caused by immunosuppressive drugs and some oncogenic infections. The aim of this study is to show the incidence of post-transplantation malignancy in patients who had surgery and were followed up in the Organ Transplant Center, Medical Park Antalya, Antalya, Turkey. METHOD: The study was based on 2100 kidney transplantation patients who had surgery between May 2008 and December 2012 and also on 1900 patients who had surgery by members of our team in other centers and who were followed up routinely. In all of our patients, the type of malignancy, the time that malignancy developed, immunosuppressive regimens, and viral status (Epstein-Barr virus and cytomegalovirus) were investigated. RESULTS: Malignancy was developed in 30 patients (60% of them were male, median age was 52.1 years). Post-transplantation malignancy development time was a median of 5.1 years. The types of malignancies were as follows: non-melanoma skin cancer in 12 patients (40%), urogenital cancer in 7 patients (24%), breast cancer in 4 patients (14%), lymphoproliferative disease in 3 patients (10%), thyroid cancer in 2 patients (6%), and lung cancer in 2 patients (6%). DISCUSSION: In this study, we did not find any increased post-transplantation malignancy risk in our patients. This finding could be due to the low-dosage immunosuppressive protocols that we used.

The Usefulness of Early Surgical Rib Stabilization in Flail Chest.

BACKGROUND: Flail chest is a clinical condition observed in patients with blunt thorax trauma. Surgical stabilization methods performed on selected patients shorten the durations of mechanical ventilation and intensive care monitoring and significantly reduce the rates of ventilator-associated morbidity and mortality. MATERIAL AND METHOD: Patients treated and diagnosed with flail chest between 2009 and 2014 were studied retrospectively. RESULTS: There were two groups: 10 patients in the group treated surgically and 10 patients in the group treated non-surgically. The groups were similar in terms of age, ISS score, degree of pulmonary contusion, number of rib fractures and location of flail chest. There were no significant differences between the stabilization and non-surgical therapy groups in hospitalization and mechanical ventilation period, tracheostomies, hospital costs and mortality. However, there were significant differences in the intensive care period. The number of the patients who developed pneumonia was significantly lower in the stabilization group, and the difference was statistically significant. CONCLUSION: Early surgical rib stabilization in flail chest is a safe treatment method which has a low complication rate and can reduce the morbidity and mortality which develop from mechanical ventilation.

Visuo-tactile integration and body ownership during self-generated action.

Although there is increasing knowledge about how visual and tactile cues from the hands are integrated, little is known about how self-generated hand movements affect such multisensory integration. Visuo-tactile integration often occurs under highly dynamic conditions requiring sensorimotor updating. Here, we quantified visuo-tactile integration by measuring cross-modal congruency effects (CCEs) in different bimanual hand movement conditions with the use of a robotic platform. We found that classical CCEs also occurred during bimanual self-generated hand movements, and that such movements lowered the magnitude of visuo-tactile CCEs as compared to static conditions. Visuo-tactile integration, body ownership and the sense of agency were decreased by adding a temporal visuo-motor delay between hand movements and visual feedback. These data show that visual stimuli interfere less with the perception of tactile stimuli during movement than during static conditions, especially when decoupled from predictive motor information. The results suggest that current models of visuo-tactile integration need to be extended to account for multisensory integration in dynamic conditions.

Systemic administration of an antagomir designed to inhibit miR-92, a regulator of angiogenesis, failed to modulate skeletal anabolic response to mechanical loading.

The goal of this study is to evaluate if promotion of angiogenesis by systemic treatment with an antagomir against miR-92a, a well established inhibitor of angiogenesis, will maximize the benefits of exercise on bone. Ten week old female C57BL6/J mice were subjected to two weeks of external load by four point bending. During the first week of mechanical loading (ML), mice were injected (2.7 mg/kg of bodyweight) with antagomir against miR-92 or control antagomir (3 alternate days via retro-orbital). No difference in tissues weights (heart, kidney, liver) were found in mice treated with miR-92 vs. control antagomir suggesting no side effects. Two weeks of ML increased tibia TV, BV/TV and density by 6-15 %, as expected, in the control antagomir treated mice. Similar increases in the above parameters (7-16 %) were also seen in mice treated miR-92 antagomir. Administration of miR-92 antagomir was effective in reducing levels of mir-92 in heart, liver and skeletal muscle and in contrast, expression levels of two other microRNA's miR-93 and miR-20a remain constant, thus suggesting specificity of the antagomir used. Surprisingly, we failed to detect significant changes in the expression levels of vascular genes (VEGF, CD31 and Tie2) in heart, liver or skeletal muscle. Based on these findings, we conclude that systemic administration of antagomir against miR-92 while reduced expression levels of miR-92 in the tissues; it did not significantly alter either angiogenic or osteogenic response, thus suggesting possible redundancy in miR-92 regulation of angiogenesis.

Bone response to loading in mice with targeted disruption of the cartilage oligomeric matrix protein gene.

Exercise induced bone response although established, little is known about the molecular components that mediate bone response to mechanical loading (ML). In our recent QTL study, we identified one such possible molecular component responding to ML: cartilage oligomeric matrix protein (COMP). To address the COMP role in mediating ML effects on bone formation, COMP expression was evaluated as a function of duration and age in response to ML in female B6 mice. A 9N load was applied using a four-point bending device at 2Hz frequency for 36 cycles, once per day for 2-, 4- and 12-days on the right tibia. The left tibia was used as an internal control. Loading caused an increase in COMP expression by 1.3-, 2- and 4-fold respectively after 2-, 4- and 12-days of loading. This increase was also seen in 16 and 36-week old mice. Based on these findings, we next used COMP knockout (KO) mice to evaluate the cause and effect relationship. Quantitative analysis revealed 2 weeks of ML induced changes in vBMD and bone size in the KO mice (5.9 % and 21 % vs. unloaded bones) was not significantly different from control mice (7 % and 24 % vs. unloaded bones). Our results imply that COMP is not a key upstream mediator of the anabolic effects of ML on the skeleton.

Comparison of paired exchange kidney transplantations with living related kidney transplantations.

OBJECTIVE: Paired-exchange kidney transplantation (PETx) gains an importance because it is difficult to find suitable organs. The aim of this study was to compare biochemical and clinical parameters of PETx with those of living-related kidney transplantation (LRTx). METHOD: The 57 PETx included 18 female and 39 male recipients among 1081 LRTx in 360 females and 721 males (N = 1138) whose operations were performed between November 21, 2008, and March 1, 2011. These two groups were compared for graft and patient survival, rejections, serum creatinine levels, glomerular filtration rates (GFRs), and other biochemical parameters. RESULTS: The PETx patients were older than the LRTx patients (45.4 ± 13.2 years versus 40.9 ± 13.5 years; P = .014). HLA mismatch was higher in the PETx group (4.7 ± 0.7 versus 3.56 ± 1.6; P = .000). First- and second-year serum creatinine and GFR values were similar between the two groups. Acute rejection episodes (PETx: 13/57; LRTx: 226/1081, P = .925), patient loss (0/57 versus 34/1081; P = .174) and graft loss (1/57 versus 55/1081; P = .257) were similar between the two groups. CONCLUSION: Our study showed similar biochemical and clinical findings of PETx versus LRTx over 2 years posttransplantation.

Hepatitis B surface antigen positivity is not a contraindication for living kidney donation.

Because of the organ shortage, the number of patients awaiting kidney transplantation has increased rapidly requiring physicians to implement new methods to increase the number of grafts. In this study, we compared clinical and biochemical parameters of patients who received kidneys from hepatitis B surface antigen-positive (group 1) versus other living related kidney donors (group 2). The study included 414 female (15 group 1 and 399 group 2) and 816 male (20 group 1 and 796 group 2) donors for 1195 living related kidney transplantations performed between April 21, 2008 and March 1, 2011. Group 1 kidney transplantations were undertaken only if the recipient displayed a hepatitis B antibody titer >10 mIU/mL and donor hepatitis B virus (HBV) DNA was negative. Demographic characteristics, 1- and 2-year serum creatinine levels, glomerular filtration rates (GFR), and liver function test results were similar between the 2 groups. There were no new HBV infections throughout the study period. Acute rejection rates (7/35 in group 1 vs 232/1195 in group 2; P = .988), graft loss (1/35 in group 1 vs 55/1195 in group 2; P = .624), and patient loss (0/35 in group 1 vs 34/1195; P = .311) were similar between the 2 groups. Our study showed that hepatitis B surface antigen positivity was not a contraindication to living kidney donation.

Comparison of the protoscolocidal effectiveness of hypertonic saline, povidone-iodine and albendazole solutions in an experimental lung hydatid cyst model.

Secondary hydatidosis is an important problem encountered during the surgical treatment of hydatid cysts. This study describes an experimental model of secondary hydatidosis by cyst inoculation, used to explore whether simultaneous inoculation of protoscolocidal agents could prevent secondary hydatidosis. Fertile cyst fluid was injected into the pleural space of rabbits alone (group 1, n = 8), and in combination with 2% albendazole solution (group 2, n = 8), 20% hypertonic saline (group 3, n = 8) or 10% povidone-iodine (group 4, n = 8). Computed tomography imaging of the thorax, indirect haemagglutination (IHA) titres and eosinophil counts were used to determine cyst development. After 16 months, three control rabbits had pneumothorax, seven had cysts and four had parenchymal nodules. Histopathological investigation of nodules revealed 87.5% cyst formation. Pleural thickening was observed in rabbits from all groups. Cyst formation rates, IHA titres and eosinophilia counts were higher in group 1 than in groups 2-4. This study demonstrated the experimental formation of secondary hydatidosis and found that topical protoscolocidal agents were beneficial in preventing cyst recurrence.

Tissue leptin levels in patients with breast cancer.

PURPOSE: High leptin serum levels, overexpression of leptin and its two main receptor isoforms, OBR-L and OBR-S, have been documented in breast cancer patients. In the present study, the relationship between tissue leptin levels and breast cancer was evaluated. METHODS: Thirty-three normal breast tissue samples and 33 breast cancer tissue samples from 33 patients with breast cancer were evaluated. The association of tissue leptin levels and important prognostic factors related to breast cancer was analyzed. RESULTS: Mean tissue leptin levels in breast cancer tissue samples (5.02 + or - 1.06 pg/ml) were significantly higher than those found in normal breast tissue (2.02 + or - 0.83 pg/ml; p=0.01). No correlation was found in tissue leptin levels and menopausal status, hormone receptor and HER-2/neu status, lymph node involvement, and histopathologic features. CONCLUSION: High leptin levels were significantly higher in breast cancer tissue compared with normal tissue. No special correlation was found between tissue leptin levels and different clinicopathological characteristics.

Relapse patterns and related prognostic factors in patients with mobile tongue cancer treated with postoperative radiotherapy.

PURPOSE: To retrospectively assess prognostic factors and patterns of relapse in patients with oral tongue cancer treated by adjuvant radiotherapy (RT). PATIENTS AND METHODS: Between 1995 and 2005, 65 patients with stage II-IV oral tongue cancer were treated with postoperative adjuvant RT at our institution. The influence of multiple patient- and treatment-related factors on local and regional control, and overall survival (OS), locoregional failure- free survival (LRFFS) and cause-specific survival (CSS) were evaluated. Median patient follow-up was 74 months. RESULTS: Five-year disease-free survival (DFS), LRFFS and CSS rates were 56, 60 and 58%, respectively. During the study period 27 (41.5%) patients had locoregional failures. Seventeen of the recurrences were in the primary tumor region, 4 in the neck, 6 in both regions. Most of the local failures occurred in the first year (median 13 months, range 5-15). Gender, T stage, stage (AJCC TN stage), surgical margin, localization of tumor, and hemoglobin level had predictive value for improved local-regional control in univariate analysis. In total, 35 deaths occurred: 28 patients died of progressive disease, one patient died due to another primary tumor (esophageal cancer) and 6 patients died of other causes. CONCLUSION: Local failure was the most important problem concerning the final outcome. High local recurrence rates and poor survival rates are important issues in the management of oral tongue cancer. Further strategies should be directed to enhancing cure rates.

Incidence and management of acute endophthalmitis after intravitreal bevacizumab (Avastin) injection.

INTRODUCTION: The aim of this study was to report the incidence and management of acute endophthalmitis after intravitreal injection of Avastin (bevacizumab), and visual acuity outcomes of three eyes of three patients who developed acute endophthalmitis following intravitreal injection of Avastin. METHODS: This clinical retrospective, non-comparative study included 3022 intravitreal injections of 1.25 mg bevacizumab consecutively performed for 1822 eyes with exudative age-related macular degeneration and other retinal diseases. Of 3022 injections, 1200 were reinjections. After clinical appearance of post-injection endophthalmitis, immediate intervention was performed, including injection of intravitreal antibiotics and early pars plana vitrectomy. RESULTS: Three eyes of three patients with acute postoperative endophthalmitis were identified in the first week following intravitreal injections of 1.25 mg bevacizumab. Among of these patients, two cases were culture-positive and one case was culture-negative. Compared with presenting visual acuities, all of three patients improved at the end of follow-up time. The overall incidence rate of post-injection culture-proven endophthalmitis was 0.066%. DISCUSSION: Acute culture-proven endophthalmitis is still a potential complication of intravitreal bevacizumab injection (approximately 0.066%) despite using maximal sterile techniques. Acute post-injection endophthalmitis following intravitreal bevacizumab occurs rapidly and can result in severe loss of vision. Prompt recognition and treatment are key in maximizing outcomes in patients who developed endophthalmitis after intravitreal injection of bevacizumab.

The effect of intravitreal bevacizumab (avastin) administration on systemic hypertension.

AIMS: To determine the short-term effect of intravitreal bevacizumab administration on systemic blood pressure levels of patients and to evaluate the safety of the drug in these patients. METHODS: Study population was divided into two groups: group A comprised patients who had hypertension and were under medication with antihypertensive drugs; group B comprised patients with normal blood pressure and were not under medication with antihypertensive drugs. All patients were graded according to their blood pressure levels before single dose of bevacizumab (0.05 ml; 1.25 mg) injection, and at day 1 and weeks 1, 3, and 6 thereafter. The blood pressure levels were analysed using repeated measures of analysis of variance (ANOVA). A P-value of <0.05 was considered significant. RESULTS: The study population included 82 patients with a mean age of 67.2+/-5.2 years. In group A, the systolic blood pressure levels showed significant increases at weeks 1, 3, and 6 (P=0.001, P<0.001, and P=0.003, respectively) compared with baseline. Similarly, diastolic blood pressure levels were significantly higher at weeks 3 (P<0.001) and 6 (P=0.016). In group B, the mean systolic and diastolic blood pressure levels showed significant elevations only at week 3 (P=0.004 and P<0.001, respectively). The percentages of both group A and B patients with normal blood pressure decreased at week 3 compared with baseline (P<0.001 and P=0.012 for groups A and B, respectively). CONCLUSIONS: The findings of this study show that there is a risk of disregulation of blood pressure levels or persistence of hypertension in hypertensive patients after intravitreal bevacizumab injections.

Synovial lymphoid neogenetic factors in Behçet's synovitis: do they play a role in self-limiting and subacute course of arthritis?

OBJECTIVE: Lymphoid neogenesis seems to play an important role in the persistence of chronic inflammation and has been shown in various disorders characterized by chronic inflammation including rheumatoid arthritis. Arthritis of Behçet's disease is characterized by non-erosive arthritis in which the disease course is considered to be subacute and self limiting. However, molecular mechanisms underlying those features of Behçet's arthritis have not been defined yet. In order to determine the contribution of lymphoid neogenesis in the disease course of Behçet's arthritis, we investigated the synovial fluid (SF) levels of CXCL 12, CXCL 13, CCL 21 homeostatic chemokines and the percentage of SF naive lymphocytes expressing their receptors such as CXCR4+ and CCR7+. We further measured the SF TGF-Beta and INF-Beta levels which are known to contribute lymphoid neogenesis via leading persistent expression of CXCR4 on T cells and inhibiting T cell apoptosis, respectively. METHODS: Fifty-one [15 BD, 17 RA, and 19 osteoarthritis (OA)] patients with at least one- sided knee arthritis were enrolled in the study. Patients with BD constituted the study group, and RA, OA patients were used as positive and negative control groups, respectively. The SF levels of CXCL 12, CXCL 13, CCL 21, TGF-Beta and INF-Beta were measured by ELISA. CXCR4, CCR7 chemokine receptors on SF lymphocytes were tested by Flow- cytometry. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis where appropriate. RESULTS: Synovial fluid CCL 21 levels were found to be increased in RA patients as compared to BD and OA patients (p = 0.003, and p = 0.013, respectively). No significant difference was detected between BD and OA patients with respect to CCL 21 levels. Both CXCL 12 and CXCL 13 SF levels were found to be higher in RA and BD patients as compared to OA patients (CXCL-12; p = 0.012, and p = 0.024), (CXCL 13; p < 0.001, and p = 0.007). However, no difference with regard to SF levels of both CXCL 12 and CXCL 13 were found between RA and BD patients. Percentages of both CD3+CXCR4+ lymphocytes and CD3+CCR7+ lymphocytes in the SF of RA patients were detected to be increased as compared to those of BD and OA patients (CD3+CXCR4+; p = 0.019, p = 0.048, respectively), (CD3+CCR7+; p = 0.023, p = 0.001, respectively). However, no differences with respect to the percentages of SF lymphocytes expressing CD3+CXCR4+ or CD3+CCR7+ were found between BD and OA patients. Both TGF-Beta and INF-Beta SF levels were found to be higher in RA patients as compared to BD and OA patients (TGF-Beta; p = 0.041, and p = 0.003), (INF-Beta; p = 0.012, and p = 0.016). However, no differences with regard to SF levels of both TGF-Beta and INF-Beta were found between BD and OA patients. CONCLUSION: Considering the subacute, self limiting and non-erosive course of arthritis observed in BD, our finding of detection of lower levels of CCL21 and TGF-Beta1 and IFN-Beta in BD patients, seems to prevent the development of LN and chronic inflammation in Behçet's synovitis. In support of this view, percentages of SF naïve T lymphocytes were found to be lower in BD patients comparing with those of the RA. Absence of tertiary lymphoid structures in BD patients, may explain the spontaneous resolution of Behçet's arthritis in most of the cases.

Dendritic cell subsets and type I interferon system in Behçet's disease: does functional abnormality in plasmacytoid dendritic cells contribute to Th1 polarization?

OBJECTIVE: Several lines of evidence point to a polarized T-helper-1 (Th1) immune response in Behçet's disease (BD). However, it is not yet clear which factors are involved in the proposed Th1 mediated pathogenesis of BD. Dendritic cells (DCs) are antigen presenting cells which play a crucial role in the polarization of immune response. No previous study has examined the possible role of DCs in the pathogenesis of BD. We conducted both quantitative and functional analysis of the peripheral blood DC subsets in BD patients with different clinical presentations. METHODS: Thirty-eight patients with BD, 12 healthy controls (HC), and 12 patients with undifferentiated spondylarthritis (uSpA) were enrolled in the study. Peripheral blood DC subsets were analysed by flow cytometry and were further characterized for maturation with CCR7. Serum levels of interferon (IFN)-alpha and IFN-b were measured by ELISA. RESULTS: BD patients had a decreased percentage of plasmacytoid DCs (pDCs) compared to HC (p = 0.036). IFN-alpha levels were found to be increased in BD patients as compared to HC and uSPA (p < 0.001, p = 0.005, respectively). BD patients had decreased levels of IFN-Beta as compared to HC and uSpA (p = 0.013, p = 0.004, respectively). No difference was found between HC and patients with uSpA regarding IFN-Beta levels. Subgroup analysis of BD patients disclosed normalization of percentage of pDCs and the level of IFN-Beta in patients receiving IFN-alpha-2b. CONCLUSION: We suggest abnormalities in pDCs and type I IFNs appear to be a master switch leading to the pathogenicity in BD by directing immune response towards Th1.