Macular choroidal thickness, volume, and vascularity index in patients with systemic sclerosis.

PURPOSE: The aim of this study was to investigate choroidal parameters in patients with systemic sclerosis (SSc) using enhanced depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT) and to determine their relationships with clinical variables and ocular features. METHODS: Thirty-three patients with SSc and 40 controls were enrolled. The groups did not differ with regard to age, sex, and axial length. The mean choroidal thickness and volume were obtained in each conventional Early Treatment of Diabetic Retinopathy Study grid subfield. The choroidal vascularity index (CVI), which provides a quantitative analysis of vasculature by calculating the proportion of the luminal area (LA) to the total choroidal area (TCA), was determined. RESULTS: Lower choroidal thickness and volume were observed in the SSc group. The CVI was significantly higher in SSc patients, whereas the TCA, LA, and stromal area were significantly lower in the SSc group; however, the significant difference of the stromal component was more pronounced than that of the luminal component. Regression analyses did not identify any clinical factors associated with the CVI (except Ca-blocker use), central macular thickness, or volume. No significant differences in choroidal parameters were found within the SSc subtypes (diffuse cutaneous systemic sclerosis (dcSSc) vs. limited cutaneous systemic sclerosis (lcSSc)), or between eyes stratified according to SSc pattern (early, active, or late) using nailfold capillaroscopy (p > 0.05 for all). CONCLUSION: Our results, with notably higher CVI values, may shed new light on choroidal impairment in patients with SSc. Stromal involvement appeared to dominate the vascular component.

Peripapillary choroidal vascularity index and thickness in patients with systemic sclerosis.

Introduction: Patients with systemic sclerosis (SSc) present an increased risk of developing glaucomatous optic neuropathy (GON). We investigated peripapillary choroidal parameters and peripapillary retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography (SD-OCT) to determine the relationships of these factors with clinical variables. Methods: A total of 33 patients with SSc were enrolled and compared to 40 controls. After obtaining circular scans around the optic disc, the global and quadrant peripapillary choroidal thickness (pCT) and RNFL thickness were measured. Additionally, the peripapillary choroidal vascularity index (pCVI), which allows for a quantitative analysis of the choroidal vasculature, was determined. Results: No significant differences were found in pCT and RNFL thickness between patients with SSc and controls, or within SSc subtypes (diffuse cutaneous systemic sclerosis (dcSSc) compared to limited cutaneous systemic sclerosis (lcSSc)) (p > 0.05). The pCVI was significantly lower in patients with SSc than in control subjects (64.25 ± 1.94 vs.65.73 ± 2.12, p < 0.001). Conclusion: Our results suggest that the statistically significant decrease in pCVI in patients with SSc compared to the control group is probably due to a decrease in the vascular layer, which would partially explain an increased risk of GON in patients with SSc.

Purtscher-like Retinopathy in a Patient with Systemic Sclerosis: A Case Report and Narrative Review.

Purtscher-like retinopathy (PLR) is an uncommon occlusive microangiopathy associated with various systemic conditions. We report a case of PLR related to severe progressive systemic sclerosis (SSc), an autoimmune disease characterized by widespread angiopathy and fibrosis, in a 44-year-old Caucasian male diagnosed with early diffuse cutaneous systemic sclerosis (dSSc). Upon ophthalmological examination, pathognomonic fundoscopy abnormalities were found. Spectral domain optical coherence tomography (SD-OCT), angio-OCT, and visual field results are documented at initial diagnosis and follow-up visits. The detailed ophthalmological assessment is juxtaposed with rheumatological evaluation and treatment. Current literature on probable pathophysiological mechanisms is reviewed in accordance with the described case. The PLR seems to be connected to severe SSc-related angiopathy initiated by capillary endothelial damage, with ultimate arteriolar precapillary occlusion in the inner retinal layer. Although this is not routinely recommended, we suggest that ophthalmological examinations may be advantageous in patients with SSc, as serious eye pathology may be present despite the lack of symptoms reported by the patient. Patients with PLR require a differential diagnosis and regular follow-up. Proper treatment of the underlying disease may have beneficial effects on the natural course of PLR.

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.

Comparison of hyaluronic acid in patients with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus.

INTRODUCTION: The aim of the present study was to determine and compare the concentration of hyaluronic acid (HA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and its correlation with parameters of disease activity and duration. The hypothesis was that HA should be increased in rheumatic diseases. We also expected that HA could be a marker of disease activity and inflammation in some of these diseases. MATERIALS AND METHODS: The study group comprised 149 patients with RA, SSc and SLE hospitalized in the Department of Rheumatology and Internal Diseases, Medical University of Bialystok (Bialystok, Poland) and 30 healthy controls. The concentrations of HA, C-reactive protein (CRP) and rheumatoid factor (RF) were measured using Architect ci8200; haemoglobin, platelets on Sysmex XS-800i; and erythrocyte sedimentation rate (ESR) on Sediplus S 2000 analysers. Statistical analysis was performed using Statistica 13.3 PL. RESULTS: Hyaluronic acid was increased in RA, SLE and SSc when compared to controls (P < 0.001, P = 0.011, and P = 0.015, respectively). There were no differences in HA between rheumatic diseases (P = 0.840). Hyaluronic acid positively correlated with SLE activity (P = 0.025). In RA, HA positively correlated with ESR (P = 0.028) and CRP (P = 0.009). However, HA was not found to correlate with the duration of rheumatic diseases. CONCLUSIONS: Hyaluronic acid concentration undergoes changes in rheumatic diseases with no difference between RA, SLE and SSc. In RA, HA concentration can be a marker of inflammation, while in SLE patients an indicator of disease activity.

Assessment of Lacrimal Duct Patency in Patients Undergoing Endoscopic Medial Maxillectomy.

PURPOSE: The risk of epiphora after medial maxillectomy with lacrimal duct transection is difficult to assess. The data available in the literature are inconclusive due to various operating techniques used by the authors of medical publications, different additional procedures aimed at improving tear drainage after maxillectomy, and a variety of lacrimal duct patency assessment techniques. The aim of our work was to assess the anatomical and functional patency of lacrimal ducts after medial maxillectomy without performing additional procedures to improve tear drainage as well as comparison of the results obtained with different assessment tests. MATERIALS AND METHODS: 21 patients who underwent medial maxillectomy in the years 2016-2019 were assessed for discomfort and epiphora based on patients' own reports and basic clinical examination, lacrimal duct rinse test, the Munk score, and a modified endoscopic Jones I test. RESULTS: Gradually increasing the sensitivity of the assessment method resulted in an increase in the number of patients with potential tear drainage disorders, starting from 0% in the rinsing test, 4.8% self-reported tearing complaints, 14.3% Munk score, and 19% modified endoscopic Jones I test. CONCLUSIONS: The study results revealed that a small fraction of patients tend to report epiphora as a consequence of medial maxillectomy themselves. Subtle functional disorders, which are not particularly bothersome to patients, are more common. More sensitive lacrimal duct patency tests reveal more cases of tear drainage disorders. The results of studies assessing the incidence of epiphora after medial maxillectomy appear to depend on the type of test used.

Expression of LIGHT/TNFSF14 and Its Receptors, HVEM and LTßR, Correlates with the Severity of Fibrosis in Lacrimal Sacs from Patients with Lacrimal Duct Obstruction.

INTRODUCTION: Fibrosis is one of the factors contributing to the development of primary acquired lacrimal duct obstruction (LDO). LIGHT (homologous to lymphotoxins, exhibiting inducible expression and competing with herpes simplex virus glycoprotein D for herpes virus entry mediator [HVEM]), a receptor expressed by T lymphocytes, has recently emerged as a new regulator of connective tissue remodeling and fibrotic response. The purpose of this study was to evaluate the role of LIGHT in the pathogenesis of LDO through: (1) assessment of expression of LIGHT and its two receptors, HVEM and LTßR (lymphotoxin ß receptor), and (2) investigation of potential relationships between expression of LIGHT and its receptors and clinical and histopathologic features. METHODS: Lacrimal sacs of 30 patients undergoing endoscopic dacryocystorhinostomy because of LDO were assessed intraoperatively and histopathologically with respect to inflammation and fibrosis. Expression of LIGHT, HVEM and LTßR was assessed by immunohistochemistry using specific antibodies and evaluated semiquantitatively using a four-grade scoring system. RESULTS: All investigated molecules, LIGHT/TNFSF14, HVEM and LTßR, were expressed in biopsies from all patients. The most prominent expression was seen within inflammatory infiltrates. Expression of LIGH, HVEM and LTßR correlated significantly with the intensity of fibrosis and duration of the disease. In multivariate analysis only LIGHT showed a significant relationship with fibrosis (ß coefficient = 0.759, p = 0.02). There was no significant correlation between expression of any molecule and other demographic or clinical features. CONCLUSION: We assume that LIGHT along with its receptors may be a factor contributing to fibrosis and synechiae formation in the lacrimal sac. This assumption needs to be proven in a future study in a group of patients who fail to improve after the first operation.

Diagnostic Power of Galectin-3 in Rheumatic Diseases.

BACKGROUND: The purpose of our study was to assess the diagnostic power of galectin-3 and compare its between rheumatic diseases and with routinely used tests such as CRP and ESR. METHODS: Eighty-two patients with rheumatoid arthritis (RA), 49 patients with systemic sclerosis (SSc), and 18 patients with systemic lupus erythematosus (SLE) were enrolled in this study. The control group comprised 30 healthy controls. Serum galectin-3 concentration was measured using immunochemical method. RESULTS: The galectin-3 concentration were significantly elevated in the RA, SSc, and SLE in comparison to the controls (p = 0.000, p = 0.000, p < 0.001; respectively). However, there were no significant differences in the serum galectin-3 levels between rheumatic diseases (H = 0.395, p = 0.821). In RA and SSc patients, galectin-3 positively correlated with erythrocyte sedimentation rate (R = 0.332, p = 0.004; R = 0.384, p = 0.009; respectively). ROC analysis revealed that galectin-3 had an excellent diagnostic power in RA (AUC = 0.911) and SSc (AUC = 0.903) and very good for SLE (AUC = 0.859). CONCLUSION: We concluded that diagnostic power of serum galectin-3 is as great as CRP and ESR in rheumatic diseases and it can be a very good laboratory marker in RA and SSc patients and a useful tool in the diagnosis of SLE.

Transferrin isoforms analysis by capillary electrophoresis in systemic lupus erythematosus and systemic sclerosis.

The systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are a diseases in which disturbances in plasma proteins glycosylation exist. The aim of the study was to compare the serum profile of transferrin isoforms between SLE and SSc. The study was carried out in 38 patients with SLE and 43 patients with SSc. Transferrin isoforms were analyzed by capillary electrophoresis method. Among the transferrin isoforms only the level of pentasialotransferrin in SLE patients was significantly higher than in SSc patients (p = .014). The median concentrations of trisialotransferrin and pentasialotransferrin were significantly lower in SLE patients (p < .001, p = .042; respectively) and SSc (p = .001, p < .001; respectively) than in the healthy subjects. In contrast, the level of tetrasialotransferrin manifested significant increase in comparison to the controls (p < .001 for all comparisons). The serum profile of transferrin isoforms alters in SLE and SSc but only level of pentasialotransferrin differs between SLE and SSc patients. We confirm that the serum profile of transferrin isoforms in SLE and SSc is unique to these diseases.

Serum profile of transferrin isoforms in rheumatoid arthritis treated with biological drugs.

BACKGROUND: In the chronic inflammation process in the course of rheumatoid arthritis (RA), many alterations in the expression of plasma proteins, as well as their posttranslational modifications (including glycosylation) can occur. Taking into account the disturbances in protein glycosylation and the emerging new treatment regimens, the aim of this study was to assess the serum profile of transferrin isoforms in RA patients treated with biological drugs. METHODS: The study included 20 patients (16 females and 4 males; mean age: 53.4 years; range: 24-67) with rheumatoid arthritis treated with rituximab. Serum samples were taken 3 times: before and 3 and 6 months during treatment. The isoforms of transferrin were separated by capillary electrophoresis (MINICAP electrophoretic system, Sebia, France) into five major fractions: asialo-, disialo-, trisialo-, tetrasialo- and pentasialotransferrin. The results were calculated as relative concentrations of each fraction. RESULTS: The median trisialotransferrin relative concentrations after 3 and 6 months treatment (4.40% and 4.10%, respectively) were significantly higher (p = 0.013, p = 0.009, respectively) than before treatment (3.50%). The levels of serum pentasialotransferrin were also increased 3 and 6 months following treatment (16.5% and 17.7%, p = 0.005 and p = 0.006, respectively) as compared to those before therapy (14.5%), while tetrasialotransferrin concentrations were lower (80.3% and 78.4%, p = 0.009 and p = 0.008, respectively) than before treatment (81.5%). Trisialotransferrin relative concentration correlated with Hb (p = 0.019), whereas pentasialotransferrin with PLT (p = 0.036) after treatment. CONCLUSIONS: This study indicates that treatment with rituximab of RA patients alters the serum profile of transferrin isoforms. Tri-, tetra- and pentasialotransferrin relative concentrations measurements can be a useful tool to monitor therapy.

The Profile of Serum Transferrin Isoforms in Rheumatoid Arthritis.

INTRODUCTION: Transferrin, a microheterogeneous iron-transporting N-glycoprotein, is an optimal model for the analysis of the glycosylation profile in rheumatoid arthritis (RA). The aim of this study was to assess the transferrin isoforms profile in RA patients at the time of diagnosis and then look into their associations with disease activity. METHODS: Serum samples were collected from 48 patients with RA. The patients were males (6) and females (42) (age range: 33-85 years). Control group consisted of 30 healthy volunteers. Transferrin isoforms were analysed by capillary electrophoresis on MINICAP electrophoretic system. RESULTS: There was a significant decrease in the relative concentrations of trisialo- (mean ± SD; 2.130 ± 1.112) and pentasialotransferrin (13.562 ± 3.088), and significant increase in tetrasialotransferrin (83.640 ± 3.165) in RA patients when compared to the control group (3.615 ± 1.156; 76.840 ± 5.621; 18.610 ± 6.027, respectively) (U Mann-Whitney test: p < 0.001 for all comparisons). There were no significant changes in the disialotransferrin concentrations in RA patients. Trisialotransferrin concentration correlated with RA activity expressed as DAS 28 in RA patients (p < 0.001). The low trisialotransferrin concentration was also associated with high platelet count and high ESR (p < 0.001 for both). Disialo-, tetrasialo- and pentasialotransferrin concentrations did not correlate with DAS 28. CONCLUSIONS: In patients with RA the serum profile of transferrin isoforms is altered. We predict that the levels of trisialylated isoforms of transferrin will serve as a useful biochemical marker of the RA activity.

Increased expression of the TNF superfamily member LIGHT/TNFSF14 and its receptors (HVEM and LTßR) in patients with systemic sclerosis.

OBJECTIVES: This study aimed to assess the potential role of the TNF superfamily member lymphocyte T-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) in SSc through evaluation of: skin expression of LIGHT and its receptors, herpesvirus entry mediator and lymphotoxin ß-related receptor, and serum concentration of LIGHT in SSc patients. METHODS: Expression of LIGHT and its receptors was investigated by immunohistochemistry and evaluated semi-quantitatively in skin biopsies from 19 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using ELISA in 329 patients with SSc and 50 control subjects. RESULTS: Expression of LIGHT and both receptors was higher in SSc patients compared with controls (P < 0.05 for all comparisons). Patients with early SSc (⩽ 3 years from the first non-Raynaud's phenomenon symptom) showed higher expression of LIGHT and herpesvirus entry mediator compared with patients with longer disease duration (P < 0.05 for both comparisons). The mean serum concentration of LIGHT was significantly higher in SSc patients compared with the controls (P < 0.05). High serum concentration of LIGHT was associated with male sex, presence of digital ulcers, muscle involvement (defined by elevated serum creatine kinase levels), steroid treatment and lack of ACA. However, in multivariate regression analysis only presence of digital ulcers and creatine kinase elevation were independently associated with serum concentration of LIGHT. CONCLUSION: These data provide the first evidence of overexpression of LIGHT and its receptors in SSc and suggest that the LIGHT axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc.

Plasma lipidomic profile signature of rheumatoid arthritis versus Lyme arthritis patients.

OBJECTIVES: Distinguishing of rheumatoid arthritis (RA) and Lyme arthritis (LA) is difficult, because of similar symptoms. This presents a significant clinical problem since treatments are quite different in both diseases. We investigated the plasma phospholipid profiles of RA and LA patients versus healthy subjects to find metabolic changes responsible for differentiation of both diseases. METHODS: Plasma was collected from 9 RA, 9 LA, and 9 healthy subjects. Extracted lipids were analyzed using LC- MS/MS to characterize phospholipid profiles of RA, LA and healthy subjects. Principal components analysis (PCA), partial least squares-discriminate analysis (PLS-DA) and variable importance in projection (VIP) scores were used to estimate the importance of each phospholipid variable. RESULTS: We identified 114 phospholipids in plasma. Phospholipid profiles were significantly different in RA and LA patients than in healthy subjects. Principal discriminant phospholipids between RA and LA groups were LPE (14:0), LPC(14:0) PI(18:0/20:4), PI(18:2/18:0), PI(16:1/18:2), PI(18:1/18:0), and PI(18:0/20:3). CONCLUSIONS: Our study provides insights into the alteration of the plasma phospholipid profile of LA patients, resulting from Borrelia burgdorferi infection, that may lead to improved LA diagnosis and differentiation of this disease from RA. Furthermore, LPE (14:0) was found to have a high potential to be a possible biomarker of LA.

Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis.

OBJECTIVE: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. METHODS: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. RESULTS: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. CONCLUSIONS: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis / Independência de isoformas de transferrina deficiente em carboidrato e peptídeos citrulinados cíclicos na artrite reumatoide

ABSTRACT Objective: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. Methods: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. Results: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. Conclusions: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

RESUMO Objetivo: Avaliar a relação entre os dois tipos de modificações pós-translacionais de proteínas na AR: glicosilação no caso da transferrina deficiente em carboidrato (TDC) e citrulinação por meio dos anticorpos no caso do antipeptídeo citrulinado cíclico (anti-CCP). Métodos: O estudo foi feito em 50 pacientes com AR. A TDC foi medida com o teste imunonefelométrico N Latex CDT e os resultados foram apresentados em unidades absolutas e relativas. O anti-CCP foi mensurado com o método quimioluminescente e o fator reumatoide (FR) pelo método imunoturbidimétrico. Resultados: Dos pacientes com AR, 80% foram positivos para anti-CCP, 70% para FR e 62% para ambos (anti-CCP e FR). A percentagem de transferrina total (%TDC) esteve significativamente elevada, mas o nível absoluto de TDC não esteve alterado. A concentração média de TDC absoluta foi maior nos pacientes anti-CCP positivos do que naqueles anti-CCP negativos. A TDC (concentração absoluta e relativa) não se correlacionou com o anti-CCP e o FR. No entanto, o FR sérico se correlacionou significativamente com o anti-CCP. O percentual de TDC não se correlacionou com o anti-CCP, mas seu nível absoluto se correlacionou com o anti-CCP apenas em pacientes FR negativos e anti-CCP negativos. A TDC não se correlacionou com o FR, somente com o anti-CCP em pacientes anti-CCP negativos. O anti-CCP se correlacionou com o DAS 28 apenas nos pacientes com AR anti-CCP negativos, mas a TDC (unidades absolutas e relativas) se correlacionou com o DAS 28 quando considerados todos os pacientes com AR e em pacientes com AR anti-CCP positivos. Conclusões: Esses resultados sugerem que as alterações na TDC e as concentrações de anti-CCP não estão associadas e indicam a independência dessas modificações pós-translacionais na artrite reumatoide. Apenas as alterações na glicosilação da transferrina refletem a atividade da AR.

Changes of glycosylation of IgG in rheumatoid arthritis patients treated with methotrexate.

PURPOSE: In patients with active rheumatoid arthritis (RA) decrease of galactosylation is correlated with disease activity. The aim of our study was to evaluate an effect of methotrexate therapy on glycosylation disturbances of IgG in RA patients. MATERIALS/METHODS: IgG glycosylation in 40 patients with active RA treated with methotrexate for 12 months prior to and after treatment were compared. The control group consisted of 20 healthy volunteers. IgG glycosylation was assessed using biotinylated lectins and immunosorbent ELISA assay. For galactose specificity Datura stramonium lectin (DSA), for sialic acid Sambucus nigra (SNA) and Maackia amurensis (MAA) and for fucose residue Areulia auranta (AAA) lectins were used. RESULTS: In RA-cases N-glycan galactosylation and sialylation of IgG before treatment were significantly lower than in healthy subjects (for DSA, MAA lectins p<0.001 and SNA p<0.05). Significant increase of IgG galactosylation and sialylation in RA patients after therapy (for DSA, MAA and SNA lectin p<0.05) was detected. Moreover the glycosylation disturbances of N-glycan IgG were strongly associated with changes of disease activity based on disease activity score. For fucose residues significantly higher absorbency of AAA lectin in RA patients before treatment was observed compared to control subjects (p<0.05) and slightly, not significantly decreased after MTX therapy. CONCLUSIONS: Defect of galactosylation of IgG in RA patients is a useful marker of disease activity that may be used for the assessment of therapy effectiveness. The role of IgG fucosylation and sialylation in RA pathogenesis has still to be determined.

The onset of lipid peroxidation in rheumatoid arthritis: consequences and monitoring.

Several epidemiological studies propose the association of rheumatoid arthritis (RA) with oxidative stress. The aim of this study was to estimate the possible onset of systemic lipid peroxidation in RA patients and its relevance for pathophysiology and monitoring of RA. Seventy-three patients with RA and 73 healthy subjects were included in the study. Lipid peroxidation was estimated by the measurement of 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal, malondialdehyde, acrolein, crotonaldehyde, 4-oxononenal, and isoprostanes (8-isoPGF(2α)) levels. Cytosolic phospholipase A(2) (cPLA(2)), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) activities and vitamin E levels were also determined. In parallel, the plasma levels of phospholipid arachidonic acid (AA), linoleic acid (LA), and 4-HNE-protein adducts were monitored. Plasma of RA patients had increased vitamin E levels, but decreased GSH-Px activity and phospholipid AA and LA levels when compared to levels of the healthy subjects. The levels of aldehydes were significantly increased in the plasma of the RA patients and even more in urine. Significant increases in HNE-modified protein adducts was observed for the first time in plasma of RA patients, while the activities of PAF-AH and cPLA(2) were decreased. The 8-isoPGF(2α) levels were 9-fold higher in plasma and 3-fold higher in urine of RA patients and were related to the severity of disease. The levels of lipid peroxidation products in plasma and in urine suggest the relationship between lipid peroxidation and the development of RA. Additionally, urine 8-isoPGF(2α), plasma 4-HNE and 4-HNE-protein adducts appear to be convenient biomarkers to monitor progression of this autoimmune disease.

Sialic acid level reflects the disturbances of glycosylation and acute-phase reaction in rheumatic diseases.

In the rheumatic diseases, the changes in the carbohydrate part of serum glycoproteins occur and these abnormalities can be monitored by serum level of total and free sialic acid. The aim of this study was to evaluate the total and free sialic acid level as a marker of inflammation activity (TSA) and the changes in glycosylation of blood glycoproteins (FSA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Studies were carried out in 50 patients with RA, 24 with SLE and 32 with SSc. TSA concentration was measured with an enzymatic, colorimetric method and FSA with a thiobarbituric method. The serum levels of TSA in RA and SLE patients were significantly increased compared to controls and in RA patients were higher than that in SSc patients. The mean serum level of FSA in RA patients was significantly higher, but in SSc patients significantly lower than that in the controls, and in RA patients was significantly higher than in SLE and in SSc patients. All acute-phase proteins were changed: Positive acute-phase proteins were elevated, and the negative protein was decreased. The positive acute-phase proteins positively correlated with the levels of TSA and FSA in RA and SSc patients. In SLE patients, TSA positively correlated with haptoglobin and α1-antitrypsin. In RA patients, there was the positive correlation of TSA and FSA with DAS 28. The changes in the serum levels of TSA and FSA in the course of rheumatic diseases could reflect the abnormalities in glycosylation/sialylation patterns of glycoproteins induced by acute-phase response.

Salivary antioxidants in patients with systemic sclerosis.

BACKGROUND: In spite of relatively large amount of evidence that oxidative stress is implicated in the pathogenesis of systemic sclerosis, there is no study analyzing antioxidants profile of the saliva of these patients. The aim of this study was to compare salivary antioxidants in subjects with systemic sclerosis and the healthy controls. METHODS: The unstimulated and stimulated salivary flow and the specific activity of peroxidase, superoxide dismutase 1, the total amount of uric acid, and total antioxidant status were determined in two subgroups of systemic sclerosis women and healthy controls. RESULTS: A significant increase in the specific activity of peroxidase, a significant decrease in the total amount of uric acid and total antioxidants status in unstimulated saliva as well as a significant increase in all antioxidants examined in stimulated saliva of group with normal salivary flow rate as compared to the healthy controls were observed. Our results showed a significant decrease in the specific activity of peroxidase in unstimulated and a significant decrease in all antioxidants examined in stimulated saliva of the group with hyposalivation as compared to the group with normal salivary flow rate. CONCLUSIONS: Our results prove that impairment of the salivary glands in the course of systemic sclerosis may be attributed to free radicals, and it is correlated with disease duration.

The changes in monosaccharide composition of immunoglobulin G in the course of rheumatoid arthritis.

The objective of this study was to determine whether galactosylation of immunoglobulin G (IgG) in patients with rheumatoid arthritis (RA) correlates with severity and duration of illness. Serum IgG glycosylation from 50 patients with RA in comparison with 30 healthy controls was analyzed. IgG from sera was isolated and monosaccharide composition was determined by means of gas chromatography. Ratio of galactose to mannose content was calculated. Patients were divided into groups according to three different criteria: disease duration, severity of RA (disease activity score index), and radiological degree of advancement of illness according to Steinbrocker. In patients with RA, significant decrease (p<0,01) of galactose ratio was observed in comparison with healthy control. In patients with long duration of RA (more than 15 years), significant decrease of galactose (p<0.05) ratio in comparison with patients who have had arthritis for less then 5 years was observed. For the group of patients with severe RA, we found reduction of galactose (p<0.001) ratio vs the group of patients in remission. For those patients who had radiological stage IV according to Steinbrocker, IgG galactose (p<0.01) content per oligosaccharide chain were also more decreased than in those patients who had stage I RA. Decreased galactosylation and of IgG in RA was observed. The lack of this carbohydrate component of IgG correlates with severity and duration of RA and could be used in monitoring the progression in early arthritis.