Proteomic analysis of human placental syncytiotrophoblast microvesicles in preeclampsia.

BACKGROUND: Placental syncytiotrophoblast microvesicles (STBM) are shed into the maternal circulation during normal pregnancy. STBM circulate in significantly increased amounts in preeclampsia (PE) and are considered to be among contributors to the exaggerated proinflammatory, procoagulant state of PE. However, protein composition of STBM in normal pregnancy and PE remains unknown. We therefore sought to determine the protein components of STBM and whether STBM protein expressions differ in preeclamptic and normal pregnancies. Patients with PE (n = 3) and normal pregnant controls (n = 6) were recruited. STBM were prepared from placental explant culture supernatant. STBM proteins were analyzed by a combination of 1D Gel-LC-MS/MS. Protein expressions levels were quantified using spectral counts and validated by immunohistochemistry. RESULTS: Over 400 proteins were identified in the STBM samples. Among these, 25 proteins were found to be differentially expressed in preeclampsia compared to healthy pregnant controls, including integrins, annexins and histones. CONCLUSION: STBM proteins include those that are implicated in immune response, coagulation, oxidative stress, apoptosis as well as lipid metabolism pathways. Differential protein expressions of STBM suggest their pathophysiological relevance in PE.

Neurosjögren: early therapy is associated with successful outcomes.

BACKGROUND: Primary Sjögren syndrome (PSS) is a systemic autoimmune condition with an estimated prevalence of 0.6%. The frequency of neurologic manifestations in PSS varies widely from 0% to 60%. METHODS: We report the characteristics of PSS patients with neurologic involvement seen at a single tertiary hospital in Singapore. Eight consecutive women (median age, 51 years [range, 38-67 years]) with neurologic manifestations of PSS seen between March 2009 to June 2011 were followed up for a mean duration of 19 months from the onset of neurologic manifestations. RESULTS: Six of 8 patients with neurosjögren had their neurologic manifestation at time of PSS diagnosis. The lag times of neurologic manifestations from PSS diagnosis for the remaining 2 patients were 9 and 30 years, respectively. Sicca symptoms were not readily volunteered as a presenting complaint in the majority of patients. All our patients received early aggressive therapy with pulse corticosteroids and intravenously administered cyclophosphamide. The mean duration from initial presentation to initiation of treatment was 11 days (1-26 days). All achieved good recovery regardless of the type or site of neurologic involvement, initial erythrocyte sedimentation rate, immunoglobulin and complement levels. CONCLUSIONS: Neurologic disease, when present, is a strong contributor to disease activity and damage. Confirmatory tests should be conducted early regardless of the presence of sicca symptoms. Vigilance for the development of new neurologic symptoms is imperative even in chronic, apparently stable patients. It is likely that early initiation of treatment contributed to good recovery in our patients.

The autoimmunity conundrum: clotting or inflammation.

Antiphospholipid syndrome (APS) is an autoimmune condition with a myriad of clinical manifestations ranging from cardiovascular, neurologic, renal involvement to cutaneous manifestations and thrombocytopenia. We describe a young woman who presented with fever, cough and dyspnea. She had a history of recurrent pregnancy losses and her antiphospholipid antibodies and lupus serologies were positive. Echocardiography showed mobile mitral and aortic valve vegetations. She was treated as for infective endocarditis and diagnosed with primary APS with lupus-like disease. Vigilance is required to establish if there is an underlying rheumatological condition in a patient who presents with presumptive infective endocarditis in the absence of risk factors. Treatment for systemic lupus erythematosus and primary APS are distinct.

In vivo pro- and anti-inflammatory cytokines in normal and patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, deforming arthritis that can lead to disabilities and poor quality of life. Cytokines are protein mediators of inflammation and are produced as a result of the activation of various cellular reactions. They are the final mediators and/or regulators of the inflammatory process. MATERIALS AND METHODS: The sera from 64 RA patients were assayed for both Th-1 and Th-2 related cytokines and soluble TNF-alpha receptors (IFN-gamma, TGF-beta, TNF-alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, sTNF-R1 and sTNFR2) using ELISA. RESULTS: The pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-18 and TNF- alpha) were significantly elevated in RA patients, while TGF-beta, an immunomodulatory cytokine, was elevated in control individuals. When the RA patients were categorised as active or inactive based on DAS scores, similar cytokines profiles were observed in both RA sub-groups. However, assays of sTNF-R1 and sTNFR-2 were noted to be significantly elevated in inactive RA patients when compared to active patients. CONCLUSION: Our findings indicate that local production of cytokine inhibitors is capable of diminishing disease activity and cytokine activity.

A comparison of the EuroQol-5D and the Health Utilities Index mark 3 in patients with rheumatic disease.

OBJECTIVE: To compare the performance of 2 commonly used utility-based health-related quality of life (HRQoL) instruments [the EuroQol-5D (EQ-5D) and Health Utilities Index mark 3 (HUI3)] in patients with rheumatic disease. METHODS: Consecutive outpatients with rheumatic diseases were interviewed twice within 2 weeks using a standard questionnaire containing the EQ-5D, HUI3, and the Medical Outcome Study Short-Form 36 Health Survey (SF-36, used to categorize health status) and assessing clinical and demographic characteristics. EQ-5D and HUI3 utility scores were compared and their construct validity and test-retest reliability were examined by comparing these scores in groups differing in health status and using intraclass correlation coefficients (ICC), respectively. RESULTS: EQ-5D and HUI3 utility scores in 114 patients differentiated well between varying health states; e.g., patients with higher SF-36 vitality scores had better EQ-5D and HUI3 utility scores (mean: 0.79 for both instruments) than patients with lower vitality scores (mean: 0.68 and 0.69, respectively) (p < 0.01 for both comparisons). ICC values for the EQ-5D and HUI3 were 0.64 and 0.75, respectively (n = 90, median interval: 7 days). EQ-5D and HUI3 utility scores were similar (mean +/- SD: 0.75 +/- 0.21 vs 0.76 +/- 0.17, p = 0.647, paired t test) and showed moderate correlation (Spearman's r: 0.45, p < 0.001). Differences were present in patients' responses to these 2 instruments: e.g., 12 patients reporting no problems with mobility (EQ-5D item) reported different levels of disability with ambulation (HUI3 item). CONCLUSIONS: The EQ-5D and HUI3 performed equally well in measuring utility-based HRQoL in patients with rheumatic disease, although they measured slightly different, though related, dimensions of health.

Do English and Chinese EQ-5D versions demonstrate measurement equivalence? An exploratory study.

BACKGROUND: Although multiple language versions of health-related quality of life instruments are often used interchangeably in clinical research, the measurement equivalence of these versions (especially using alphabet vs pictogram-based languages) has rarely been assessed. We therefore investigated the measurement equivalence of English and Chinese versions of the EQ-5D, a widely used utility-based outcome instrument. METHODS: In a cross-sectional study, either EQ-5D version was administered to consecutive outpatients with rheumatic diseases. Measurement equivalence of EQ-5D item responses and utility and visual analog scale (EQ-VAS) scores between these versions was assessed using multiple regression models (with and without adjusting for potential confounding variables), by comparing the 95% confidence interval (95%CI) of score differences between these versions with pre-defined equivalence margins. An equivalence margin defined a magnitude of score differences (10% and 5% of entire score ranges for item responses and utility/EQ-VAS scores, respectively) which was felt to be clinically unimportant. RESULTS: Sixty-six subjects completed the English and 48 subjects the Chinese EQ-5D. The 95%CI of the score differences between these versions overlapped with but did not fall completely within pre-defined equivalence margins for 4 EQ-5D items, utility and EQ-VAS scores. For example, the 95%CI of the adjusted score difference between these EQ-5D versions was -0.14 to +0.03 points for utility scores and -11.6 to +3.3 points for EQ-VAS scores (equivalence margins of -0.05 to +0.05 and -5.0 to +5.0 respectively). CONCLUSION: These data provide promising evidence for the measurement equivalence of English and Chinese EQ-5D versions.