Could IL-1ß, IL-6, IFN-γ, and sP-selectin serum levels be considered as objective and quantifiable markers of rheumatoid arthritis severity and activity?

Objectives: Rheumatoid arthritis (RA) is a multisystem, chronic, T-cell-mediated disease in which immunological abnormalities result in symmetrical small joint inflammation, articular destruction due to synovitis, and extra-articular organ involvement. An important role in the pathogenesis of RA is attributed to a combination of genetic factors and environmental triggers. Literature data on the utility of circulating IL-1ß, IL-6, IFN-γ, and sP-selectin concentration evaluation depending on the activity and advancement of RA seems to be inconclusive. The aim was a case-control study evaluating IL-1ß, IL-6, IFN-γ, and sP-selectin concentrations in 77 RA patients dependent on the Steinbrocker classification as well as the disease activity score with examination of 28 joints (DAS28), and compared to 30 control subjects. Material and methods: Serum IL-1ß, IL-6, IFN-γ, and sP-selectin concentrations were measured using ELISA kits. Results: The concentrations of all molecules tested, except for IL-1ß, were significantly different from the control group. Univariate logistic regression analysis indicated that their levels significantly influenced the likelihood of RA diagnosis. Differences between IL-1ß, IL-6, IFN-γ, and sP-selectin concentrations dependent on the disease activity assessed on the basis of the DAS28 score, as well as the severity of the disease assessed based on the Steinbrocker classification, were not observed. IL-6 positively correlated with the DAS28 score. Conclusions: Among the tested molecules, only IL-6 positively correlated with the DAS28 score. Thus, we postulate that next to C-reactive protein and the erythrocyte sedimentation rate, also IL-6 could be clinically relevant and possibly reflects RA activity. Because recently the IL-6 concentration can be determined in applied in vitro diagnostic tests, it presents us with the possibility to test this protein as a marker of RA activity in routine laboratory practice.

IL-6 Quotient (The Ratio of Cerebrospinal Fluid IL-6 to Serum IL-6) as a Biomarker of an Unruptured Intracranial Aneurysm.

BACKGROUND: Studies conducted so far have focused mainly on the assessment of IL-6 levels in patients with ruptured brain aneurysms. Carrying out detailed studies in patients with un-ruptured brain aneurysms (UIA) would be extremely important, as it would answer the question of whether IL-6 plays also a role in primary aneurysm formation and growth. METHODS: IL-6, S100, NSE, and albumin concentrations in 67 UIA patients and 17 individuals without vascular lesions in the brain were tested using in vitro diagnostic immunoassays according to the manufacturers' instructions. IL-6 Quotient was calculated by dividing cerebrospinal fluid (CSF) IL-6 by serum IL-6. RESULTS: We showed that IL-6 Quotient was significantly higher in UIA patients (1.78) compared to the control group (0.87; p<0.001). Multivariate logistic regression analysis demonstrated that a growth in IL-6 Quotient increases the probability of UIA diagnosis. In UIA patients CSF IL-6 concentration was significantly higher (4.55 pg/ml) compared to the serum concentration (2.39 pg/ml; p<0.001). In both the study and control group, the blood-brain barrier was intact, thus the CSF-blood gradient of the IL-6 concentration in UIA patients was likely to be the expression of local synthesis of the cytokine within the central nervous system. Patients with multiple brain aneurysms had significantly higher CSF IL-6 levels (5.08 pg/ml) compared to individuals with a single aneurysm (4.14 pg/ml; p=0.0227). CONCLUSION: This totality of the may suggest IL-6 as a biomarker for UIA formation; however, further studies are needed to unequivocally confirm clinical application of IL-6 concentration evaluation.

Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour.

INTRODUCTION: Taking into account the possibility of myelin-associated proteins having a role in brain tumour development, the study aimed to evaluate the diagnostic usefulness of myelin-associated proteins (Nogo-A, MAG, OMgp) released into extracellular space in patients with brain tumours. PATIENTS AND METHODS: Protein concentration in primary brain tumour (n = 49) and non-tumoural subjects (n = 24) was measured in cerebrospinal fluid (CSF) and serum by means of ELISA. Immunohistochemistry for IDH1-R132H was done on 5-µm thick formalin-fixed, paraffin-embedded tumour sections with the use of an antibody specific for the mutant IDH1-R132H protein. RESULTS: The receiver operator characteristic curve analysis showed that CSF Nogo-A and serum MAG were useful in differentiating patients with primary brain tumour from non-tumoural individuals. This was also true in the case of the separate analysis of the astrocytic tumour versus non-tumoural groups and the meningeal tumour versus non-tumoural groups. Neither Nogo-A nor MAG or OMgp concentrations were significantly different, in serum or CSF, between IDH1 wild-type astrocytic brain tumour patients compared to IDH1 mutant patients. CONCLUSIONS: Our results indicated the potential usefulness of CSF Nogo-A and serum MAG evaluation as circulating biomarkers of primary brain tumours. Because blood is relatively easy to obtain, future research should be conducted to explicitly indicate the value of serum MAG concentration evaluation as a brain tumour biomarker.Key messagesMyelin-associated proteins may be circulating brain tumour biomarkers.Nogo-A and MAG proteins seem to be the most useful in brain tumour diagnosis.Decreased CSF Nogo-A concentration is an adverse prognostic factor for patients' survival.

Training in intraoperative neuromonitoring of recurrent laryngeal nerves reduces the risk of their injury during thyroid surgery.

INTRODUCTION: Even though incidence of recurrent laryngeal nerve palsy (RLNP) is low, it affects importantly the quality of life of patients and remains one of main medicolegal litigation problems in surgery. Intraoperative neuromonitoring (IONM) has become widely accepted tool helping in recurrent laryngeal nerve identification, however no clear association of IONM with RLNP rate has been demonstrated. The aim of our study was to assess whether training in IONM influences rates of RNLP after thyroid surgery as an independent factor. MATERIAL AND METHODS: We analysed retrospectively 1235 patients who underwent thyroidectomy at the 1st Department of General and Endocrine Surgery, Medical University of Bialystok. Possible risk factors for RLNP were evaluated: application or not of IONM, the extent of surgery or thyroid pathology in correlation with surgeons' experience in IONM (trained or untrained). RESULTS: There were 2351 nerves at risk (NAR) and 39 RNLP were diagnosed after thyroid surgery (1.66%). Surgeons trained in IONM performed 52.2% of all operations (1200 NAR) with 7 RLNP (0.58%), whereas not-trained had 32 RLNP for 1151 NAR (2.8%; p < 0.001). After 182 thyroidectomies (357 NAR) guided by IONM (14.7%) 3 RLNP were observed (0.84%) vs. 36 palsies per 1994 NAR without IONM (1.81%; p = 0.189). The highest danger of RLNP was reported after reoperations and the lowest after subtotal thyroidectomies. We found no association between thyroid pathology and RLNP rate. CONCLUSIONS: According to our study training in IONM decreases chances of RLNP especially during total or near total thyroidectomy.

Lipid profile disturbances may predispose psoriatic patients to liver dysfunction.

INTRODUCTION: Psoriasis is a chronic inflammatory disease associated with metabolic disturbances and liver dysfunction. Both serum fatty acids (FA) and ceramides (Cer) have structural functions but also are signal molecules that could be involved in the pathogenesis of liver dysfunction. AIM: To assess the concentration of the circulating FA and Cer in correlation with the alanine aminotransferase (ALT) blood level in psoriatic patients. In addition, we have examined the relationship between ALT concentration and severity of the disease and inflammation markers. MATERIAL AND METHODS: Eighty-five patients with psoriasis and 32 healthy controls were enrolled in the study. Patients were divided into 2 groups according to ALT blood levels. Serum concentration of 14 FA and 14 Cer were measured by gas-liquid chromatography. The results were correlated with the Psoriasis Area and Severity Index (PASI), serum lipid profile, and inflammatory markers. RESULTS: We observed higher PASI score (p = 0.01) and higher C-reactive protein (p = 0.02) concentration in the group of psoriatic patients with high ALT. Serum ALT positively correlated with saturated fatty acids (SFA) (p = 0.01, r = 0.27) and SFA/unsaturated fatty acids (UFA) ratio (p = 0.01, r = 0.26). ALT negatively correlated with UFA level (p = 0.008, r = -0.28). Lignoceric ceramide positively correlated with ALT level (r = 0.22; p = 0.045) in psoriatic patients. CONCLUSIONS: Patients with severe psoriasis are predisposed to the development of liver dysfunction. We have demonstrated disturbances of serum fatty acid and sphingolipid profile in psoriatic patients, which may trigger liver disease.

Elastography of Endometrium in Women Taking Tamoxifen: A New Approach to an Old Diagnostic Problem.

Tamoxifen is a commonly used selective estrogen receptor modulator applied in the treatment for breast cancer. However, in the endometrium, Tamoxifen stimulates tissue growth, cellular transformation, the migration of the cells, and metastatic potential in endometrial cancer. Considering that uterine cancer is the most common neoplasm of the reproductive tract and the third most common neoplastic disease in women, the aim of this study was to investigate if applying elastography in examining the endometrium was beneficial for uterine cancer screening protocols in women on selective estrogen receptor modulator therapy. This study was based on the execution of a classic assessment of the endometrium that included the evaluation of the following: echogenicity, central endometrial stripe, presence of fluid in the uterine lumen, myometrium-endometrium interface, intensity of vascularization and vascular pattern. An ultrasound presentation was then processed and analyzed with elastography. The values of the elastography parameters demonstrated good consistency for the measurement of the softest endometrial layer thickness in elastography. A strong positive correlation (R = 0.56) was demonstrated between the endometrial thickness, as determined by ultrasound examination, and the softest endometrial layer in elastography (p < 0.001). The research showed that the elastography measurements of the width of the softest endometrium layer, based on a population of women taking Tamoxifen, appeared to be a promising option for endometrial cancer screening.

Ratio of IL-8 in CSF versus Serum Is Elevated in Patients with Unruptured Brain Aneurysm.

Only scarce data pertaining to interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) chemokines in human aneurysm can be found in the current literature. Therefore, the aim of this study was the evaluation of cerebrospinal fluid (CSF) and serum IL-8 and MCP-1 concentration in unruptured intracranial aneurysm (UIA) patients (n = 25) compared to the control group (n = 20). IL-8 and MCP-1 concentrations were measured with ELISA method. We demonstrated that CSF IL-8 concentration of UIA patients is significantly higher (p < 0.001) than that presented in the serum, which can indicate its local synthesis within central nervous system. CSF IL-8 concentration was also significantly related to aneurysm size, which may reflect the participation of IL-8 in the formation and development of brain aneurysms. IL-8 Quotient (CSF IL-8 divided by serum IL-8) in UIA patients was statistically higher compared to control individuals (p = 0.045). However, the diagnostic utility analysis did not equivocally indicate the diagnostic usefulness of the IL-8 Quotient evaluation in brain aneurysm patients. Nevertheless, this aspect requires further study.

Abnormal serum fatty acid profile in psoriatic arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with higher risk of cardiovascular events and metabolic syndrome than psoriasis without arthritis. Fatty acids (FA) play an important role as signaling molecules in inflammatory and metabolic pathways. The aim of the study was to evaluate serum FA concentration in patients with PsA and to investigate the correlations of FA with the clinical and biochemical markers. MATERIAL AND METHODS: We measured 14 FA serum concentrations by gas-liquid chromatography and flame-ionization detector after direct transesterification in 54 psoriatic patients (including 14 PsA patients) and 32 healthy controls. FA were divided according to their biologic properties into: saturated FA (SFA) and unsaturated FA (UFA), subdivided into monounsaturated FA (MUFA) and polyunsaturated FA (PUFA). RESULTS: The results were correlated with Psoriasis Area and Severity Index (PASI), inflammatory and biochemical markers and lipid profile. We observed an abnormal FA profile in both psoriasis and PsA. We demonstrated lower concentrations of 10 FA in psoriasis and 7 in PsA. Patients with joint disease had a significantly higher percentage of SFA (p = 0.016) and MUFA (p = 0.001) and lower percentage of PUFA (p < 0.001) than the control group. The SFA/UFA ratio was significantly higher (p = 0.02) in PsA than in psoriasis and the controls. In the group of PsA the concentrations of docosahexaenoic acid (DHA) (p = 0.027) and n-3 PUFA (p = 0.031) correlated inversely with PASI. CONCLUSIONS: Our findings indicate a changed FA profile both in psoriasis and PsA and reflect metabolic status that may predispose to the development of metabolic syndrome.

Serum sphingolipid level in psoriatic patients with obesity.

INTRODUCTION: Psoriasis is a chronic inflammatory disease associated with metabolic syndrome, including obesity. Ceramides (CER) and sphingosine-1-phosphate (S1P), which belongs to sphingolipids, have both biological and structural functions in the human epidermis. AIM: To evaluate serum concentrations of selected CER in psoriatic patients in different weight ranges, the impact of obesity on the concentration of circulating CERs, their association with the course of psoriasis and selected inflammatory markers. MATERIAL AND METHODS: Eigthy-five patients with active plaque-type psoriasis and 32 healthy controls were enrolled in the study. Patients were divided into 3 groups: normal weight, overweight and obese. Serum concentrations of 14 ceramides were measured by gas-liquid chromatography. The results were correlated with the Psoriasis Area and Severity Index (PASI), serum lipid profile and inflammatory markers. RESULTS: There were no significant differences in total serum CER concentration between psoriatic groups of patients. The S1P concentration was higher in psoriatic patients with normal body weight and overweight than in the control group (p = 0.002 and p = 0.04, respectively). In psoriatic patients with normal body weight, nervonic ceramide (C24:1) correlated with PASI (r = 0.38; p = 0.042) and CRP (C-reactive protein) (r = 0.42; p = 0.023). In overweight patients, the concentration of lignoceric ceramide (C24:0) correlated inversely with the severity of the disease (r = -0.41; p = 0.022) and CRP (r = -0.6; p = 0.0004). CONCLUSIONS: We have demonstrated an abnormal sphingolipid profile in psoriatic patients in different weight groups. Selected CER might be the biomarkers of psoriasis severity and inflammation, may reflect lipid disturbances and contribute to the development of metabolic syndrome.

Lysosomal exoglycosidases and cathepsin D in colon adenocarcinoma.

INTRODUCTION: Changes in the structure of membrane glycoconjugates and activity of glycosidases and proteases are important in tumor formation. OBJECTIVES: The aim of the study was to compare the specific activity of lysosomal exoglycosidases: N-acetyl-ß-D-hexosaminidase (HEX), its isoenzymes A (HEX A) and B (HEX B), ß-D-galactosidase (GAL), α-fucosidase (FUC), and α-mannosidase (MAN) with the activity of cathepsin D (CD) in serum, urine, and carcinoma tissue of patients with colon adenocarcinoma. PATIENTS AND METHODS: The specific activity of HEX, HEX A, HEX B, GAL, FUC, MAN, and CD was assayed in serum, urine, and carcinoma tissue of 12 patients with colon adenocarcinoma. RESULTS: Lysosomal exoglycosidases and CD have similar specific activity in colon adenocarcinoma tissue and urine, which is higher than their activity in serum (with the exception of the highest specific activity of CD in urine). A positive correlation was observed between the specific activity of CD and that of HEX, HEX A, FUC, and MAN in the carcinoma tissue and urine as well as between CD and GAL in the urine of patients with colon adenocarcinoma. Negative correlations were observed between protein levels and the specific activity of HEX, HEX A, FUC, MAN, and CD in the carcinoma tissue and urine, and between protein levels and GAL in urine. CONCLUSIONS: Increased degradation and remodeling of glycoconjugates in the colon adenocarcinoma tissue is reflected by increased specific activity of exoglycosidases and CD. The results suggest a strong effect of exoglycosidase action on tissue degradation and a potential role of exoglycosidases in the initiation of proteolysis.