Serum miR-21 and miR-29a expression in systemic sclerosis patients.

OBJECTIVES: The aim of our study was to evaluate the expression levels of miR-21 and miR-29a in the serum of systemic sclerosis (SSc) patients and to determine their correlation with clinical and immunological parameters. METHODS: 34 patients fulfilling the ACR/EULAR 2013 classification criteria for SSc were included in the study. miR-21 and miR-29a expression levels in the serum were determined by PCR (SYBR Green technology). 2-ΔΔCt method was used for analysis. 14 healthy donors were used as controls (HCs). RESULTS: Expression levels of miR-21 were upregulated in the serum of 17 (50.0%) of the patients. The expression of miR-29a was downregulated in 15 (44.12%) of the SSc patients. Receiver operating characteristic (ROC) curve analysis was conducted in order to evaluate the diagnostic accuracy of the expression levels of the studied miRNAs in the serum. Area under the curve (AUC) for miR-21 was 0.634 (95% CI=0.479-0.790), p=0.147 with 64.7% sensitivity and 64.3% specificity. AUC for miR-29a was 0.605 (95% CI=0.420-0.790), with 64.3% sensitivity and 52.9% specificity but without statistical significance (p=0.257). The multimarker analysis of the ROC curves for both miRNAs showed AUC=0.714 (95% CI=0.569-0.860), p=0.021 with 79.4% sensitivity and 42.9% specificity. Levels of miR-29a correlated with the levels of miR-21 in the serum (with Spearman correlation coefficient 0.517, p=0.00017) and with the presence of anti-Scl70 antibodies in the serum (with Spearman correlation coefficient 0.438, p=0.010). CONCLUSIONS: Our data showed a deregulation of miR-21 and miR-29a in the serum of patients with SSc which could suggests their potential role in the disease pathogenesis. Further analysis with higher number of patients is needed to confirm if these miRNAs could be used in the clinical practice as diagnostic biomarkers as well as biomarkers for both disease activity and progression.

Severe mononeuritis multiplex in a patient with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis characterised by bronchial asthma, hypereosinophilia, and systemic vasculitis. History of asthma with blood eosinophilia and multiorgan involvement are the important clues to suspect EGPA. In the original paper by Churg and Strauss cardiac, gastrointestinal tract, renal, and neurological involvement were noted more frequently. The pattern of neurological involvement may be mononeuritis multiplex, and symmetrical and asymmetrical polyneuropathy. Mononeuritis multiplex was present in 78.1% while cranial nerves were involved in only 4.1% of cases. Glucocorticosteroids and immunosuppressants, especially cyclophosphamide, have considerably improved the prognosis and overall survival rates in patients with systemic vasculitis, including eosinophilic granulomatosis with polyangiitis. The authors present a clinical case of eosinophilic granulomatosis with polyangiitis with severe mononeuritis multiplex. The case reflects the successful application of a cyclophosphamide regime as a remission inducer.

Obesity, Echocardiographic Changes and Framingham Risk Score in the Spectrum of Gout: A Cross-Sectional Study.

OBJECTIVES: This study aims to establish cardiovascular risk in obese and non-obese patients in stages of gout by using Framingham risk score (FRS) and transthoracic echocardiography. PATIENTS AND METHODS: This single-center cross-sectional study encompassed 201 patients (160 males, 41 females; mean age 56.9±13 years; range 20 to 89 years) including 52 asymptomatic hyperuricemia, 86 gouty arthritis without tophi, and 63 gouty tophi patients. Body Mass Index (BMI) and FRS were calculated. Left atrium (LA), interventricular septum, posterior wall (PW) of the left ventricle, fractional shortening (FS), mitral annular systolic velocity (S'), mitral annular early diastolic velocity (E') and transmitral to mitral annular early diastolic velocity ratio (E/E') were measured. Data were analyzed by Kolmogorov-Smirnov test, Shapiro-Wilk test, t-test, Mann-Whitney U test, analysis of variance test and multiple linear regression models. RESULTS: There was no significant difference in FRS, FS, S', E' and E/E' between obese and non-obese patients with asymptomatic hyperuricemia, gouty arthritis without tophi or gouty tophi. Obese patients in the three disease gradations had larger LA (p=0.007, p=0.004, p=0.039) and thicker PW (p=0.002, p=0.037, p=0.007). Increased BMI independently predicted the thickening of the PW in asymptomatic hyperuricemia (R2=0.319), gouty arthritis without tophi (R2=0.093) and gouty tophi (R2=0.068). CONCLUSION: Despite the lack of difference in FRS and functional systolic and diastolic parameters between obese and non-obese patients in the spectrum of gout, morphological heart changes were more pronounced in obese patients. In gouty tophi, it is possible that higher urate load together with chronic inflammation contribute for the alterations, as obesity worsens them.

YKL-40 and cytokines - a New Diagnostic Constellation in Rheumatoid Arthritis?

BACKGROUND: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction. YKL-40 is a chitinase-like glycoprotein produced by activated macrophages, neutrophils, arthritic chondrocytes and cancer cells. It has been shown that YKL-40 is implicated in tissue remodeling, angiogenesis and inflammation. AIM: to investigate serum and synovial YKL-40 levels in relation to IL-1ß, TNF-α, and IL-6 in RA patients. MATERIALS AND METHODS: Serum and synovial concentrations of YKL-40, TNF-α, IL- 6, and IL-1ß were determined by ELISA in 39 patients (mean age 53.18 ± 16.54 yrs) with active RA. RESULTS: Serum YKL-40 levels were increased in all patients. The highest levels were found in synovial fluid (P<0.01). Our study showed a strong association between serum and synovial levels of YKL-40 and serum TNF-α and IL-1 ß (P<0.05). CONCLUSION: This is the first study finding a significant correlation between serum TNF-α and IL-1ß and YKL-40 in active RA. We suggest that these molecules together might play a dominant role in the pathogenesis and disease activity and could possibly serve as a new diagnostic constellation in rheumatoid arthritis.

Organising pneumonia - the first manifestation of rheumatoid arthritis.

Organising pneumonia (OP) is a distinct type of interstitial lung disease, because it can also be seen in association with several conditions such as infections, drugs, and connective tissue diseases. An association of OP with rheumatoid arthritis (RA) has also been described. Joint manifestations of RA usually precede lung involvements by several years; however, in less than 10% of cases of RA, interstitial lung disease may be the initial feature of RA. Organising pneumonia as the initial manifestation or developed simultaneously of RA is extremely rare, and its clinical features remain unknown. We present a 56-year-old woman with OP as the first manifestation of RA.

Evaluation of cardiovascular risk in stages of gout by a complex multimodal ultrasonography.

The aim of our work was to assess ultrasound features of cardiovascular (CV) risk in stages of gout. Cross-sectional complex multimodal ultrasound study of 169 age-matched patients, with similar distribution of arterial hypertension, diabetes mellitus, obesity and chronic renal failure, was divided into four groups: 41 with asymptomatic hyperuricemia, 52 gout without tophi, 42 gouty tophi and 34 controls with osteoarthritis. Parameters independently associated with CV risk were measured: renal resistive index (RRI), left ventricular mass index (LVMi), mitral annulus early diastolic velocity (e'), intima-media thickness (IMT) and common carotid artery resistive index (CCARI). Multivariate analyses were performed to evaluate the impact of gout stages and CV risk factors on ultrasound alterations. Gouty tophi increased the risk of having IMT >0.90 mm with an OR 11.51 (95 % CI 2.32-57.21, p = 0.003), gout without tophi raised the risk with an OR 6.25 (95 % CI 1.37-28.44, p = 0.018), while asymptomatic hyperuricemia had no effect on IMT. The category of CCARI >0.70 was influenced by tophi with an OR 11.18 (95 % CI 2.61-47.83, p = 0.001) and by arterial hypertension with an OR 3.22 (95 % CI 1.11-9.36, p = 0.032). Neither asymptomatic hyperuricemia nor gout without tophi modified the development of abnormally high CCARI. Gout stages had no impact on LVMi, e' and RRI. Tophi are related to worsened ultrasonographic parameters evaluating target organs in gout, relative to earlier stages of the disease. They create a strong risk of carotid arteries' changes even beyond arterial hypertension.

Ultrasonographic measurement of carotid artery resistive index and diastolic function of the heart in gout patients.

The aim of the study was to establish the functional disorder in the blood circulation of gout patients with a method that shows early damage of the heart and vascular structures. A total of 117 patients were examined cross-sectionally by a complex multimodal ultrasonography and were divided into four groups: 37 healthy controls, 24 asymptomatic hyperuricemia, 36 gout without tophi and 20 gouty tophi. With pulsed Doppler, common carotid artery resistive index (CCARI) and parameters of the transmitral blood flow were determined: the ratio between maximal early and late flow velocities (E/A ratio) and deceleration time (DT). With tissue Doppler imaging, mitral annular peak velocity (Em) was obtained. In the examined ultrasonographic parameters between healthy controls and the three patient groups, there was a statistically significant difference (p < 0.001). Comparing asymptomatic hyperuricemia and gout without tophi, no significant difference in CCARI (p = 0.656), E/A ratio (p = 0.472), DT (p = 0.990) and Em (p = 0.488) was found. Gouty tophi in comparison with gout without tophi and asymptomatic hyperuricemia had significantly lower Em (mean ± SD 0.07 ± 0.02 vs 0.09 ± 0.03 vs 0.13 ± 0.17) and significantly higher CCARI (mean ± SD 0.74 ± 0.05 vs 0.70 ± 0.05 vs 0.69 ± 0.05). Further multiple logistic regression revealed that tophi increased subject's likelihood of having category of CCARI ≥ 0.7 with an OR = 10.91 (95 % CI 1.80-66.14, p = 0.009), while the category of Em < 0.08 m/s was influenced by renal insufficiency with an OR = 3.07 (95 % CI 1.17-8.02, p = 0.022). Gouty tophi are associated with progression of arteriosclerotic-type vessel changes. Worsening of diastolic dysfunction of the heart is independently associated with renal insufficiency. In terms of CV risk, tophi are an indicator of its increase.

Androgen receptor (CAG)n polymorphism and androgen levels in women with systemic lupus erythematosus and healthy controls.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects mainly females. Therefore, interrelations between the reproductive and immune system have been assumed. Considering the complex influence of hormones and receptors, we aimed to investigate the influence of androgens and androgen receptor (AR) polymorphism in women with SLE. One hundred and sixteen patients and 44 healthy women were investigated. Testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulphate (DHEAS) concentrations and AR (CAG)n polymorphism were determined. SLE patients had significantly lower levels of total and free testosterone and DHEAS in comparison with the controls. No differences in the CAG repeat length between the groups were established. Women with two alleles carrying more than 22 CAG repeats had significantly higher levels of SHBG (101.51 ± 61.81 vs. 69.22 ± 45.93 nmol/l, p = 0.015) and DHEAS (3.11 ± 2.65 vs. 2.11 ± 3.06 µmol/l, p = 0.007) and a tendency to higher testosterone concentrations (2.35 ± 2.10 vs. 1.71 ± 1.70 nmol/l, p = 0.056) in comparison with other women. The CAG repeat length in the relatively longer (CAG)n allele was inversely related to the Systemic Lupus International Collaborating Clinics/ACR index (r = -0.258, p = 0.009). In conclusion, the androgen receptor (CAG)n polymorphism is not related to the development of SLE, but it could modulate the severity of the lupus chronic damages as well as the androgen levels in women.

Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis.

YKL-40, also known as human cartilage glycoprotein 39, is a member of the "mammalian chitinase-like proteins" family without chitinase activity. Increased serum concentrations are associated with inflammatory processes and several types of cancer. In this study, we evaluated YKL-40 levels in serum and synovial fluid of patients with rheumatoid arthritis in comparison with the ultrasonographic findings. YKL-40 levels were measured by enzyme-linked immunosorbent assay in 25 patients with active rheumatoid arthritis and in 40 healthy subjects. B mode and power Doppler were performed to determine synovial thickening and vascularization. Serum YKL-40 level in patients was significantly higher than the concentration in healthy controls (P < 0.01). In patients with rheumatoid arthritis, the level of the glycoprotein in synovial fluid was remarkably elevated compared to the serum level (P = 0.003). The B mode and power Doppler scores correlated to YKL-40 in serum and synovial fluid (P = 0.07). Serum YKL-40 levels were related positively to serum markers of inflammation such as C-reactive protein (P = 0.004) and erythrocyte sedimentation rate (P = 0.003). This study is the first to demonstrate a relationship between YKL-40 levels and ultrasonographic examinations in Bulgarian patients with rheumatoid arthritis. The findings suggest that YKL-40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation.

Decreased daily melatonin levels in women with systemic lupus erythematosus - a short report.

BACKGROUND: The neuroendocrine system is known to influence immunity, but the precise interactions between different hormones and autoimmune disorders remain obscure. AIMS: The present study aimed to investigate the role of daily serum melatonin concentrations in the development of systemic lupus erythematosus (SLE) in women. STUDY DESIGN: Case-control study. METHODS: One-hundred and eleven SLE female patients and 46 healthy women were included in the study. Daily serum melatonin levels were investigated in all participants. RESULTS: SLE patients showed significantly lower daily melatonin levels in comparison to healthy women during the short photoperiod (17.75±7.13 pg/mL [16.05] vs. 21.63±6.60 pg/mL [20.10], p=0.012). Hormone concentrations were inversely related to the SLE activity index (SLEDAI) (r= -0.268, p=0.004), but they did not correlate to any particular American College Rheumatology (ACR) criterion (p>0.05 for all). CONCLUSION: Daily melatonin levels were decreased in women with systemic lupus erythematosus and correlated inversely to the activity of the autoimmune disease. Further studies are needed to clarify the importance of the pineal and extrapineal melatonin secretion in patients with systemic lupus erythematosus as well as the interrelations between hormones and autoimmunity.

Outcome in a patient with systemic lupus erythematosus and concurrent chronic hepatitis B infection.

A 35-year-old Caucasian woman with proven systemic lupus erythematosus (SLE) had been effectively managed with hydroxychloroquine and methylprednisolone for many years. In 2005 she was admitted to the rheumatology clinic with a flare up of the disease and with proteinuria of 3.2 g/24 h. Renal biopsy was performed and revealed diffuse proliferative nephritis. Before the renal biopsy a positive HB(s)Ag was found with high virus replication (hepatitis B virus (HBV)-DNA-4 170 000 copies/ml). Liver biopsy revealed chronic hepatitis with minimal activity (TAIS=1). Lamivudine was administered with concomitant maintenance corticosteroid treatment, but without antimalarials. Pulsed methylprednisolone treatment for diffuse lupus nephritis was begun on the background of lamivudine therapy. The liver enzymes returned to normal values, HBV replication was suppressed, and the proteinuria disappeared. At present the patient is not being treated with lamivudine and there are no objective signs of nephritis and hepatitis, or HBV activation.