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To investigate corneal microstructure of systemic sclerosis (SSc) patients using in vivo confocal microscopy (IVCM). 33 patients with SSc and 30 age-matched healthy subjects were recruited. All participants underwent comprehensive ophthalmic examination including IVCM (Heidelberg Retina Tomograph III, Heidelberg Engineering GmbH, Heidelberg, Germany) and ocular surface evaluation. Subbasal nerve plexus morphology was investigated using automated software analysis (ACCMetrics V3; University of Manchester, Manchester, UK). Keratocyte cell densities in the anterior stroma were significantly lower in patients with SSc compared to controls (P < 0.0001). In 7 SSc patients no keratocyte nuclei were identified in the anterior stroma and in most patients scattered hyperreflective punctate material were observed in the anterior stroma. Significantly lower subbasal nerve fiber parameters were found in patients with SSc compared to healthy subjects (P < 0.05). There were no significant correlations between the duration of SSc and any of the corneal cell density values. Tear break-up time values (4.82 ± 3.15 s) and Ocular Surface Disease Index scores (33.27 ± 30.11) were abnormal, Schirmer values (6.78 ± 5.82 mm) were borderline in SSc patients. In SSc, corneal morphological changes and accumulation of punctate material in the stroma was detected with confocal microscopy. Severe ocular surface disease was observed in SSc patients with significant impairment in subbasal nerve plexus morphology resembling peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Objectives: Systemic sclerosis (SSc) is a rare, chronic connective tissue disease involving multiple organ systems, including the eye. We evaluated the detailed clinical ocular manifestations of outpatients with SSc.Methods: Demographics, disease duration and subtype, nailfold capillaroscopy (NFC) patterns and laboratory parameters encompassing the autoantibody profile of 51 SSc patients were evaluated, and a general ocular examination was performed for each participant.Results: Twenty-nine patients (56.86%) had eyelid skin alterations, 26 (50.98%) had retinal abnormalities, 26 (50.98%) had cataracts, 8 (15.69%) had conjunctival changes, 7 (13.73%) had iris abnormalities, 33 (64.71%) suffered from dry eye disease (DED), and 11 (21.57%) suffered from glaucoma. Significant positive correlations were found between NFC data and both tear breakup time and Ocular Surface Disease Index test values.Conclusions: Eyelid skin abnormalities, DED and retinal abnormalities are among the most common SSc-related ocular involvements. Diverse ophthalmic findings are attributed to the heterogeneity of SSc. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the association between clinical signs and symptoms of dry eye disease (DED) in patients with systemic sclerosis (SSc). This cross-sectional observational study included 19 SSc patients and 19 normal subjects with no ocular symptoms or ocular surface disorders. Clinical parameters included tear film break-up time (tBUT), Schirmer I, lissamine green (LG) dye, and tear film osmolarity tests, tear production, and tear secretion flow. For assessment of the dry eye symptoms, the Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients. The following mean values were found in SSc patients: OSDI 33.6 ± 19.86; osmolarity of the tear fluid 310.8 mOsmol/l ± 14.47; tBUT time 5.158 ± 2.328 s; Schirmer I test 5.395 mm/5 min; LG grading score 2.026 ± 0.8893; collected tear fluid volume 6.397 ± 2.761 µl. The calculated average tear velocity was 4.654 ± 1.963 µl/min. A significant correlation was found between the OSDI as a subjective parameter and disease duration. Early recognition of dry eye symptoms, a possible extra-intestinal manifestation of SSc, should be included in the check up of the disease to reduce ocular complications. The objective tear functional tests were strongly influenced by individual factors like age and disease duration. [ABSTRACT FROM AUTHOR]

The human precorneal tear film is a special body fluid, since it is a complex mixture of proteins, lipids, small bioactive molecules, and their concentrations and relative distribution represent not only the metabolic state of the ocular surface but also the systemic and local homeostasis of the outer eye and the human body. This suggests that biochemical analysis of the precorneal tear film composition may provide a non-invasive tool for diagnosis and monitoring of disease progression or treatment efficacy in human medicine. However, collecting tears is demanding, and obtaining reproducible and unaltered samples is challenging because of the small sample volumes of tears. Several methods are available for tear collection as a preparatory step of precorneal tear film analysis, and the collection method used has to be assessed since it has a critical impact on the effectiveness of the assays and on the quality of the results. Each sampling method has advantages and disadvantages; therefore, it is not easy to choose the appropriate collecting method for tear collection. To overcome these limitations various methods have been recommended by different authors for special aspects of specific tests. The aim of our review was to evaluate tear sampling methods with regard to our ongoing biochemical analysis. *Contributed equally. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the efficacy, reasons for switching and drug survival of TNF-α inhibitors (TNFis) used as first- and second-line drugs in ankylosing spondylitis (AS). Methods: Data on patients suffering from AS and treated with at least one TNFi between November 2005 and 2013 were extracted retrospectively from the database of a single clinical centre. Beside demographic data, the disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the response rates (BASDAI50), reasons for switching and survival curves of TNFis were analysed in general and in subgroups of patients treated with each of the available TNFis. The reasons for switching were defined as inefficacy, side effects of the given drug, patient's request and occurrence of extra-articular manifestations. Results: Altogether, 175 patients were on TNFis and 77 of them received at least two TNFis. The patients' age at the initiation of the first TNFi was higher among switchers compared to non-switchers (42.5 ± 12.6 vs. 38.8 ± 11.2 years, p = 0.049); otherwise, gender, disease duration and initial disease activity had no influence on the risk of switching. The decrease of the BASDAI was similar among non-switchers and switchers using either the first or second TNFi, but the response rates to the first and second TNFi were worse in switchers than in non-switchers. Following the failure of the first TNFi, the retention on therapy was unfavourable, especially in patients on infliximab after 1 year of treatment. The main reason for switching from the first drug was inefficacy. The frequency of side effects that led to switching was higher in the infliximab group than in patients treated with other agents. Conclusion: Although the retention rate to a second-line TNFi was somewhat worse than that to the first-line TNFi, the switching of TNFis is a good therapeutic option in AS patients who failed to respond to the first TNFi. [ABSTRACT FROM AUTHOR]

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM) > 2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6 ± 7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p = 0.003) and lupus anticoagulant (11.3% vs. 29.0%, p = 0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7 ± 369 vs. 30.9 ± 17.3 GPI, p = 0.02) and aCL IgM antibody levels (75.3 ± 357.4 vs. 9.3 ± 10.3 GPI, p = 0.02), and marginally lower aCL IgG antibody levels (9.2 ± 4.9 vs. 9.7 ± 3.9 GPI, p = 0.096). While the ECLAM score significantly correlated with hyperferritinemia ( p = 0.04), the SLEDAI score was marginally associated with hyperferritinemia ( p = 0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients. [ABSTRACT FROM AUTHOR]

Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age- and sex-adjusted prolactin concentration was assessed in 256 serum samples from lupus patients utilizing the LIASON prolactin automated immunoassay method (DiaSorin S.p.A, Saluggia, Italy). Disease activity was defined as present if European Consensus Lupus Activity Measurement (ECLAM) > 2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 4. Lupus manifestations were grouped by organ involvement, laboratory data, and prescribed medications. Hyperprolactinemia was presented in 46/256 (18%) of the cohort. Hyperprolactinemic patients had significantly more serositis (40% vs. 32.4%, p = 0.03) specifically, pleuritis (33% vs. 17%, p = 0.02), pericarditis (30% vs. 12%, p = 0.002), and peritonitis (15% vs. 0.8%, p = 0.003). Hyperprolactinemic subjects exhibited significantly more anemia (42% vs. 26%, p = 0.02) and marginally more proteinuria (65.5% vs. 46%, p = 0.06). Elevated levels of prolactin were not significantly associated with other clinical manifestations, serology, or therapy. Disease activity scores were not associated with hyperprolactinemia. Hyperprolactinemia in lupus patients is associated with all types of serositis and anemia but not with other clinical, serological therapeutic measures or with disease activity. These results suggest that dopamine agonists may be an optional therapy for lupus patients with hyperprolactinemia. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the condition of lymphatic vessel system in patients with systemic sclerosis (SSc) and determines the association of dystrophic changes and tissue damage with the lymphatic vessels changes. Identification of the lymphatic endothelial cells in skin biopsy samples from SSc patients was performed through staining for podoplanin and prox-1. Results show a severe reduction in patients' lymphatic capillaries and lymphatic precollector vessels.

This article discusses a study on the role of Rho-associated kinases (Rock) in the activation of fibroblasts in systemic sclerosis (SSc). The study used chemical inhibitors and small interfering RNA in Rock signaling and applied real-time polymerase chain reaction, Western blotting and SirCol assay in analyzing the expression of extracellular matrix (ECM) proteins and α-smooth muscle actin. It showed the effectiveness of inhibition of Rock in reducing the synthesis of the proteins.

The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean ± SD) were between 9.3 ± 4.4 to 13.7 ± 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies. [ABSTRACT FROM AUTHOR]

Background: Soluble, human low affinity Fcγ receptors, such as sFcγRII and sFcγRIII, are known to play a pathologic role in different diseases. Sandwich ELISAs had previously been applied for the specific detection and determination of these soluble receptors. In these ELISAs, commercial monoclonal antibodies (Ab) were used as capture antibodies with monoclonal or polyclonal antibodies serving as detector Abs. Increased levels of cell-free FcγRIII have been detected in patients with lupus but the functions and levels of sFcγRII have not been fully characterized yet. Objectives: The aim of this work was to determine the ligand binding capacities and levels of soluble FcγRII and FcγRIII in sera of patients with systemic lupus erythematosus (SLE). Moreover, correlation between the levels of sFcγRII and sFcγRIII and the clinical activity of the disease were investigated. Methods: Sera of 47 patients with SLE, and 51 healthy subjects were analyzed. In the newly developed indirect sandwich ELISAs commercial monoclonal anti-FcγRs are used as capture antibodies, and the ligand of FcγRII and FcγRIII, an artificial immune complex (IC), serves as a detection component replacing the second antibodies used in previous methods. Results: The ligand binding capacity of both soluble FcγRII and sFcγRIII were elevated in the sera of SLE patients compared to control samples. This increase was significant in patients with the active disease (n = 30; p < 0.01). It was also revealed that a substantial part of the soluble Fcγ receptors in these patients was bound in vivo to circulating IC. Conclusion: These newly developed ELISAs are probably more phisiologically relevant than other previous assays because they detect the circulating receptors on the basis their in vitro ligan binding capacities. Therefore this method can separately measure the levels of the soluble, free FcγRs and those bound circulating IC in vivo. [ABSTRACT FROM AUTHOR]