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ID PMID Title PublicationDate abstract
21546532 Combination of the Schirmer I and phenol red thread tests as a rescue strategy for diagnos 2011 Jul 15 PURPOSE: To define a combination of the Schirmer I and phenol red thread (PRT) tests that improves the screening of patients with ocular sicca syndrome. METHODS: The PRT test was performed before (PRT1) and after (PRT2) the Schirmer I test, in both eyes of 143 patients complaining of ocular dryness secondary to Sjögren's syndrome or sicca asthenia polyalgia syndrome (SAPS; 72 and 71 patients, respectively), and in 40 control patients. Groups were matched by age and sex. After determining the best cutoff values using the receiver operating characteristic procedure, several combinations of PRT and Schirmer I were assessed to improve the predictive values of the procedure. RESULTS: The best cutoff value for PRT2, estimated at 15 mm, provided a satisfying match between sensitivity and specificity indexes (68% and 90%, respectively), similar to those obtained with the Schirmer I test. If PRT1 alone was ineffective to screen SGS from control patients, the comparison between PRT1 and PRT2 (so-called "DeltaPRT") was found as a good marker to detect patients with persistent tear reflex. Interestingly, the combination of positive Schirmer I, PRT 2, and/or ΔPRT tests was found to be highly predictive of severe ocular sicca syndrome. CONCLUSIONS: The combination of the Schirmer I and PRT tests strongly improves the screening procedure to detect patients with ocular dryness related to Sjögren's syndrome or SAPS. It could be more widely used in daily clinical practice, aside from the Schirmer I test, to optimize the work-up of patients presenting with dry-eye subjective signs.
21385542 The minimally important difference (MID) for patient-reported outcomes including pain, fat 2011 Mar OBJECTIVES: We wanted to determine the MID for the HAQ, pain, fatigue, sleep and global VAS (0-100mm) in Sjögren's syndrome (SS) using a patient-reported overall health status anchor. METHODS: Patients with a diagnosis of primary Sjögren's syndrome (pSS) who had answered a standardised questionnaire at two consecutive visits including an overall health status question: 'How would you describe your overall status since your last visit: much better, better, the same, worse, much worse?' were included. The MID was calculated as the mean change between visits for those who rated their disease as better or worse. Scales on VAS were from 0 (best) to 100 (worst). RESULTS: Forty patients met the inclusion criteria (97% female, mean age 58 years, mean disease duration 10 years). The mean baseline HAQ was 0.68. Ten rated their status as better and 14 as worse than the previous visit. MID estimates for improvemenT/worsening (SD) respectively were: -7.4 (27.8) / 20.7 (20.0) for pain VAS, -6.2 (28.3) / 15.2 (21.8) for fatigue VAS, -24.0 (24.0) / 15.2 (28.0) for sleep VAS, -0.18 (0.23) / 0.14 (0.30) for HAQ and -23.1 (21.6) / 16.4 (20.9) for global VAS. Spearman's rho correlation coefficients for the patient-reported outcomes were 0.38 (pain VAS), 0.54 (fatigue VAS), 0.55 (sleep VAS), 0.39 (HAQ), and 0.57 (global VAS), p<0.05. CONCLUSIONS: The MID for pain and fatigue are greater for worsening than improvement. A small change in the HAQ is detected as a change in status by the patient. This knowledge may aid those who treat SS and in designing intervention studies.
22971705 A case of solitary pulmonary nodular amyloidosis with Sjögren's syndrome. 2013 Patients with Sjögren's syndrome frequently have pulmonary involvement, but the involvement of nodular pulmonary lesions, including pulmonary amyloidosis, is rare. Most cases of pulmonary amyloidosis involve multiple nodules; solitary pulmonary nodular amyloidosis, as an associated condition of Sjögren's syndrome, is very rare.In our report, we present the case of an 80-year-old female with Sjögren's syndrome who was incidentally found to have a small solitary pulmonary nodule. The nodule showed high fluorodeoxyglucose uptake and contained areas of calcification. Because the probability that the nodular lesion was malignant could not be excluded, the tumor was excised using a thoracoscopic procedure; the final diagnosis was pulmonary nodular amyloidosis. Although most cases of pulmonary amyloidosis involve multiple nodules, amyloidosis should be considered in the differential diagnosis for a solitary pulmonary nodule in patients with Sjögren's syndrome.
22859346 Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease 2012 Oct OBJECTIVE: To study the efficacy of anakinra versus disease-modifying antirheumatic drugs (DMARD) in refractory adult-onset Still's disease (AOSD). METHODS: In a 24-week study, 22 patients with AOSD taking prednisolone ≥ 10 mg/day received anakinra (n = 12) or DMARD (n = 10). The primary endpoint was achievement of remission. RESULTS: At 8 and 24 weeks, 7/12 and 6/12 receiving anakinra and 5/10 and 2/10 receiving DMARD achieved remission. Anakinra induced greater improvement in physical health measured by Medical Outcomes Study Short-Form 36 (SF-36; p < 0.011). During an open-label extension (OLE) of 28 weeks, 7/14 patients taking anakinra and 2/3 taking DMARD were in remission. CONCLUSION: Anakinra induced more beneficial responses than DMARD in patients with AOSD and was favored in the OLE phase. (ClinicalTrials.gov Protocol Registration NCT01033656).
21393509 The growth factor progranulin binds to TNF receptors and is therapeutic against inflammato 2011 Apr 22 The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFα-TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis.
22838845 Carbonic anhydrase I (CA1) is involved in the process of bone formation and is susceptible 2012 Jul 27 INTRODUCTION: Ankylosing spondylitis (AS) is characterized by abnormal bone formation in the spine and the sacroiliac joints. In vitro assays demonstrate that carbonic anhydrase I (CA1) promotes calcium precipitation. This study investigated the function of CA1 for bio-mineralization and determined if common polymorphisms in the CA1 gene might contribute to AS risk. METHODS: Calcification was induced in Saos-2 cells, a human osteosarcoma cell line, with ascorbic acid and β-glycerophosphate. Calcification was determined by Alizarin Red-S (AR-S) staining. Expressions of CA1, alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN), osterix (OSX) and runt-related transcription factor-2 (Runx2) were determined by real-time PCR and western blotting. The cells were also treated with acetazolamide, an anti-carbonic anhydrase drug. Genotyping was performed using Illumina VeraCode microarray in a case-control study including 51 AS patients, 267 rheumatoid arthritis (RA) patients and 160 healthy controls. The result was confirmed by Taqman assay, including 258 AS patients, 288 RA patients and 288 healthy controls. RESULTS: Following the induction of calcification, Saos-2 cells produced large amounts of calcium-rich deposits. Increased transcriptions of CA1, ALP, BSP, OCN, OSX and Runx2, essential genes for ossification, were detected in the cultured cells. Following treatmen with acetazolamide, the expression of CA1 obviously declined and mineralized nodule formation was also decreased. Illumina microarray indicates that SNP at rs7841425 also showed significant differences in allelic frequency (P = 0.01396) and genotypic frequency (P = 0.005902) between AS cases and controls. In addition, SNP at rs7827474 showed significant differences in allelic frequency (P = 5.83E-04) and genotypic frequency (P = 0.000186) between RA cases and controls (P values were adjusted to multiple comparisons). The Taqman assay revealed that rs725605 demonstrated statistically significant evidence of allele frequency (P = 0.022307) and gene frequency (P = 0.007731) for association with AS. This SNP did not show significant differences in allelic frequencies and gene frequencies between RA patients and controls. CONCLUSIONS: CA1 may play an essential role in bio-mineralization and new bone formation. The gene encoding CA1 is susceptible to AS.
22623451 Prevalence of autoimmune inflammatory myopathy in the first nations population of Alberta, 2012 Nov OBJECTIVE: To estimate the population-based prevalence of autoimmune inflammatory myopathy (AIM) in Alberta, Canada, with a specific focus on rates in the First Nations population. METHODS: Physician billing claims and hospitalization data for the province of Alberta (1994-2007) were used to estimate the probability of having AIM (i.e., polymyositis or dermatomyositis) based on 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors of sex, age group, and location of residence (urban or rural) in estimating the prevalence rates within the First Nations and non-First Nations populations. RESULTS: The overall prevalence of AIM was 25.0 per 100,000 persons (95% credible interval [95% CrI] 13.4-49.0) in the First Nations population and 33.8 (95% CrI 28.9-39.6) in the non-First Nations population. For both groups, prevalence was increased in women relative to men, rural women relative to urban women, and in those age >45 years. CONCLUSION: Unlike other rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, we did not detect an increased prevalence of AIM in Alberta's First Nations population relative to the non-First Nations population. Potential limitations include coding errors, underidentification of First Nations members, and recognized differences in access to care for the First Nations population.
21360521 Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production 2011 Jun OBJECTIVE: Mesenchymal stem cells (MSCs) have been proposed to be a useful tool for treatment of rheumatoid arthritis (RA), not only because of their multipotency but also because of their immunosuppressive effect on lymphocytes, dendritic cells, and other proinflammatory cells. Since bone destruction caused by activated osteoclasts occurs in RA, we undertook the present study to investigate the effect of MSCs on osteoclast function and differentiation in order to evaluate their potential use in RA therapy. METHODS: Human MSCs and peripheral blood mononuclear cells were cultured under cell-cell contact-free conditions with osteoclast induction medium. Differentiation into osteoclast-like cells was determined by tartrate-resistant acid phosphatase staining and expression of osteoclast differentiation markers. RESULTS: The number of osteoclast-like cells was decreased and expression of cathepsin K and nuclear factor of activated T cells c1 (NF-ATc1) was down-regulated by the addition of either MSCs or a conditioned medium obtained from MSCs. Osteoprotegerin (OPG) was constitutively produced by MSCs and inhibited osteoclastogenesis. However, osteoclast differentiation was not fully recovered upon treatment with either anti-OPG antibody or OPG small interfering RNA, suggesting that OPG had only a partial role in the inhibitory effect of MSCs. Moreover, bone-resorbing activity of osteoclast-like cells was partially recovered by addition of anti-OPG antibody into the conditioned medium. CONCLUSION: The present results indicate that human MSCs constitutively produce OPG, resulting in inhibition of osteoclastogenesis and expression of NF-ATc1 and cathepsin K in the absence of cell-cell contact. Therefore, we conclude that human MSCs exert a suppressive effect on osteoclastogenesis, which may be beneficial in inhibition of joint damage in RA.
23190696 Interleukin-32-induced thymic stromal lymphopoietin plays a critical role in macrophage di 2012 Nov 28 INTRODUCTION: Interleukin (IL)-32 is an inflammatory cytokine induced by Mycobacterium tuberculosis and Mycobacterium bovis in a variety of cell types and discovered in the synovial of patients with rheumatoid arthritis (RA). Thymic stromal lymphopoietin (TSLP) play several roles in the pathogenesis of RA. However, the role of IL-32 and TSLP in RA has not been elucidated. METHODS: We evaluated the specific mechanism of between IL-32 and TSLP in RA using human monocyte cell line, THP-1 cells. RESULTS: Here we documented for the first time that IL-32 highly increased TSLP production in THP-1 cells and human blood monocytes. TSLP expression was induced by IL-32 via activation of caspase-1 and nuclear factor-κB. TSLP produced by IL-32 increased differentiation of monocytes but depletion of TSLP prevented differentiation of monocytes into macrophage-like cells. Chondroprotective drugs such as chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT) decrease production of TSLP and activation of caspase-1 and nuclear factor-κB. In addition, CS and BT inhibited IL-32-induced monocytes differentiation. CONCLUSIONS: Taken together, IL-32 and TSLP are important cytokines involved in the development of RA. The effects of CS and BT were associated with the downregulation of TSLP and caspase-1 through negative regulation of IL-32 pathways in RA.
23153327 Behcet's Syndrome. 2012 Dec 3 Behcet's syndrome (BS) is a vasculitis, seen more commonly around the Mediterranean and the Far East, and manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. Its natural history of getting less severe over time, more severe disease in males and lack of specific diagnostic testing separates it from other commonly seen conditions in rheumatology. Most of the serious manifestations respond well to immunosuppression, and these are the mainstays of treatment for BS. BS is more prevalent in regions along the Silk Road, from the Mediterranean to the Far East. The genetic risk factor most strongly associated with BS is the human leukocyte antigen (HLA)-B51 allele. While genetic factors seem to play a role in the development of certain features of BS, there is general consensus that as yet unidentified environmental stimuli are necessary for initiation of disease. Proposed exogenous triggers include both bacterial and viral infections, which may then lead to dysregulation of the immune system, ultimately leading to the phenotypic expression of disease. The clinical manifestations of BS are protean in nature. While most patients develop mucocutaneous and genital ulcers along with eye disease, other patients may also present with arthritis, frank vasculitis, thrombophlebitis and CNS disease. Interestingly, the manifestations of this illness vary considerably based on gender and ethnicity. As the phenotypic expression among patients with BS is quite heterogeneous, pharmacological therapy is variable and dependent upon the severity of the disease as well as organ involvement. Treatment for BS overlaps considerably with therapies for other autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis and the vasculitides. Pharmacological agents utilized for treatment of BS include corticosteroids, colchicine, azathioprine, and tumour necrosis factor (TNF).α inhibitors, among others. In this article, we review the salient clinical studies for each drug class along with important side effects as well as drug toxicity monitoring. Management of the patient with BS is complex and oftentimes requires a multidisciplinary approach. We discuss strategies to assess and stratify patients based on clinical manifestations and disease severity. A summary of drug toxicities as they relate to the aforementioned pharmacological agents, as well as guidelines regarding vaccinations in this patient population, are offered. Finally, we conclude with treatment strategies for the common manifestations of BS along with a discussion of the management of thrombotic disease in these patients.
22834228 Summary health statistics for U.S. adults: National Health Interview Survey, 2010. 2012 Jan OBJECTIVES: This report presents health statistics from the 2010 National Health Interview Survey (NHIS) for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, education, family income, poverty status, health insurance coverage, marital status, and place and region of residence. Estimates are presented for selected chronic conditions and mental health characteristics, functional limitations, health status, health behaviors, health care access and utilization, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age-adjusted and unadjusted versions. DATA SOURCE: NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2010, data were collected on 27,157 adults in the Sample Adult questionnaire. The conditional response rate was 77.3%, and the final response rate was 60.8%. The health information for adults in this report was obtained from one randomly selected adult per family. In very rare instances where the sample adult was not able to respond for himself or herself, a proxy was used. HIGHLIGHTS: In 2010, 61% of adults aged 18 years and over had excellent or very good health. Twelve percent of adults had been told by a doctor or health professional that they had heart disease, 25% had been told on two or more visits that they had hypertension, 9% had been told they had diabetes, and 22% had been told they had some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Twenty-one percent of adults were current smokers, and 21% were former smokers. Based on estimates of body mass index, 35% of adults were overweight and 27% were obese.
21554007 Ethanol extract of Justicia gendarussa inhibits lipopolysaccharide stimulated nitric oxide 2011 Jun CONTEXT: Justicia gendarussa Burm (Acanthaceae) is a plant used to treat inflammatory diseases such as rheumatoid arthritis. However, the mechanism involved in the anti-inflammatory properties of this plant has not been studied well. OBJECTIVE: The in vitro anti-inflammatory activities of ethanol extract of Justicia gendarussa leaves (J-01) are studied here for the first time. MATERIALS AND METHODS: The ethanol extract, J-01 was prepared from the leaves of Justicia gendarussa. The inhibitory effect of J-01 in nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-9 (MMP-9) gene expressions were studied in lipopolysaccharide (LPS) stimulated macrophage cell line RAW 264.7. RESULTS: J-01 in a concentration dependent manner (200-50 μg/mL) attenuated NO production from macrophage stimulated with LPS (1 μg/mL). Further, J-01 significantly suppressed iNOS mRNA expression in these cells. J-01 has also downregulated the MMP-9 gene expression in LPS stimulated macrophage. DISCUSSION AND CONCLUSION: The modulatory function of J-01 in inhibiting NO, iNOS, and MMP-9 as obtained from the present in vitro studies provide first scientific evidence to support the anti-inflammatory properties of Justicia gendarussa. This plant may have potential use in the management of inflammatory conditions such as arthritis.
23114105 Modern psychometrics applied in rheumatology--a systematic review. 2012 Oct 31 BACKGROUND: Although item response theory (IRT) appears to be increasingly used within health care research in general, a comprehensive overview of the frequency and characteristics of IRT analyses within the rheumatic field is lacking. An overview of the use and application of IRT in rheumatology to date may give insight into future research directions and highlight new possibilities for the improvement of outcome assessment in rheumatic conditions. Therefore, this study systematically reviewed the application of IRT to patient-reported and clinical outcome measures in rheumatology. METHODS: Literature searches in PubMed, Scopus and Web of Science resulted in 99 original English-language articles which used some form of IRT-based analysis of patient-reported or clinical outcome data in patients with a rheumatic condition. Both general study information and IRT-specific information were assessed. RESULTS: Most studies used Rasch modeling for developing or evaluating new or existing patient-reported outcomes in rheumatoid arthritis or osteoarthritis patients. Outcomes of principle interest were physical functioning and quality of life. Since the last decade, IRT has also been applied to clinical measures more frequently. IRT was mostly used for evaluating model fit, unidimensionality and differential item functioning, the distribution of items and persons along the underlying scale, and reliability. Less frequently used IRT applications were the evaluation of local independence, the threshold ordering of items, and the measurement precision along the scale. CONCLUSION: IRT applications have markedly increased within rheumatology over the past decades. To date, IRT has primarily been applied to patient-reported outcomes, however, applications to clinical measures are gaining interest. Useful IRT applications not yet widely used within rheumatology include the cross-calibration of instrument scores and the development of computerized adaptive tests which may reduce the measurement burden for both the patient and the clinician. Also, the measurement precision of outcome measures along the scale was only evaluated occasionally. Performed IRT analyses should be adequately explained, justified, and reported. A global consensus about uniform guidelines should be reached concerning the minimum number of assumptions which should be met and best ways of testing these assumptions, in order to stimulate the quality appraisal of performed IRT analyses.
22029668 IL-6/IL-6 receptor system and its role in physiological and pathological conditions. 2012 Feb IL (interleukin)-6, which was originally identified as a B-cell differentiation factor, is a multifunctional cytokine that regulates the immune response, haemopoiesis, the acute phase response and inflammation. IL-6 is produced by various types of cell and influences various cell types, and has multiple biological activities through its unique receptor system. IL-6 exerts its biological activities through two molecules: IL-6R (IL-6 receptor) and gp130. When IL-6 binds to mIL-6R (membrane-bound form of IL-6R), homodimerization of gp130 is induced and a high-affinity functional receptor complex of IL-6, IL-6R and gp130 is formed. Interestingly, sIL-6R (soluble form of IL-6R) also binds with IL-6, and the IL-6-sIL-6R complex can then form a complex with gp130. The homodimerization of receptor complex activates JAKs (Janus kinases) that then phosphorylate tyrosine residues in the cytoplasmic domain of gp130. The gp130-mediated JAK activation by IL-6 triggers two main signalling pathways: the gp130 Tyr759-derived SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase-2)/ERK (extracellular-signal-regulated kinase) MAPK (mitogen-activated protein kinase) pathway and the gp130 YXXQ-mediated JAK/STAT (signal transducer and activator of transcription) pathway. Increased IL-6 levels are observed in several human inflammatory diseases, such as rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis. IL-6 is also critically involved in experimentally induced autoimmune diseases. All clinical findings and animal models suggest that IL-6 plays a number of critical roles in the pathogenesis of autoimmune diseases. In the present review, we first summarize the IL-6/IL-6R system and IL-6 signal transduction, and then go on to discuss the physiological and pathological roles of IL-6.
22695186 Endocrine alterations in primary Sjogren's syndrome: an overview. 2012 Dec Involvement of several components of the endocrine system has been proposed as significant player in primary Sjogren's syndrome (SS) pathogenesis and clinical expression. Hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been previously demonstrated in patients with primary SS as a result either of a pituitary defect and/or of adrenal gland dysfunction. In support of the latter hypothesis, antibodies to 21-hydroxylase (OH)--a marker of autoimmune adrenal disease--have been detected in sera from approximately one fifth of primary SS patients, in association with B-cell activating cytokines and adrenal hyporesponsiveness. As a result of HPA hypofunction, adrenal androgens and particularly dehydroepiandrosterone-sulfate (DHEA-S) have been reportedly low in primary SS individuals. Epithelial salivary gland cells undergo apoptosis in lack of both estrogens and active androgens. In the absence of a compensatory action of the latter, menopausal status can lead to salivary gland apoptotic process triggering an aberrant immune response. On the other hand, given that salivary gland tissue remodeling has been shown to be under androgenic control, the observed androgen deficiency in these patients might account for the observed alterations in the salivary gland architecture. Heightened serum and salivary gland tissue prolactin levels in primary SS patients have been also suggested as contributors in disease pathogenesis. Finally, autoimmune thyroid disease (ATD) occurs quiet commonly in the setting of primary SS and subclinical hypothyroidism is the main functional abnormality observed in these patients.
21962758 Leflunomide in dermatology. 2012 Apr Leflunomide is an oral disease-modifying antirheumatic drug administered to patients with rheumatoid and psoriatic arthritis. This drug inhibits dihydroorotate dehydrogenase, an enzyme critical in the production of intracellular pyrimidines, and down-regulates tumor necrosis factor-alfa activity. Leflunomide has demonstrated usefulness in treating cutaneous psoriasis along with other dermatologic and rheumatologic conditions.
21172862 Peripheral neuropathies in Sjogren syndrome: a new reappraisal. 2011 Jul BACKGROUND: The prevalence of peripheral neuropathy in patients with Sjögren syndrome remains unclear owing to conflicting results in the published series, with numbers ranging from 2% to over 60% of Sjögren syndrome patients. Whether peripheral neuropathy is a feature of the systemic or glandular disease or whether it is related to a circulating antineuronal antibody remains also uncertain. METHODS: The authors reviewed the records of patients with primary Sjögren syndrome (pSS), fulfilling the Revised European-American Classification Criteria, seen in their department from 1992 to 2009. The patients with previously recorded neuropathic features were re-examined clinically and electrophysiologically. Other causes of polyneuropathy were excluded. The authors also searched for circulating antineural antibodies using immunofluorescence and western blot and for antibodies against muscarinic and nicotinic acetylcholine receptors as potential biomarkers. RESULTS: 509 cases met the diagnostic criteria for pSS. Among these, 44 patients were recorded as having neuropathic symptoms. After completing the evaluation, however, only nine (1.8%) had polyneuropathy with objective clinical signs and abnormal electrophysiological findings. The neuropathy was axonal in all, in five pure sensory and in four sensorimotor. The patients with peripheral neuropathy had extraglandular manifestations such as palpable purpura and vasculitis. No evidence of antineural autoimmunity was found, and no candidate biomarkers were identified. CONCLUSION: Polyneuropathy is a rare manifestation of pSS occurring in 1.8% of patients. In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development.
22410397 Performance of the preliminary classification criteria for cryoglobulinaemic vasculitis an 2012 Jan BACKGROUND: Cryoglobulinaemic vasculitis (CV) is often related to hepatitis C virus (HCV) infection, but it can develop in other diseases (e.g. other infections, connective tissue diseases, malignancies) in the absence of HCV infection. A comparison of the performance of the recently published classification criteria for the CV was made between HCV-positive and HCV negative patients with serum cryoglobulins. METHODS: 500 patients with serum cryoglobulins were studied. Their mean age was 60.77±13.75 years, they were 356 females (71.2%) and 144 males (28.8%). CV was diagnosed in 272 patients (54.4%), while other diseases associated with serum cryoglobulins without CV (CwV) were diagnosed in 228 patients (45.6%). RESULTS: 117 HCV negative patients were collected (23.4%) and they were 42/272 (15.4%) among the CV group, while they were 75/228 (32.9%) among the CwV. In HCV negative patients the sensitivity and specificity of the classification criteria of CV were 89.5% CI 95% [79.5-99.5] and 90.3% CI 95% [82.8-97.8], respectively, while in HCV positive patients they were 88.3% CI 95% [83.6%-93.1%] and 96.1% CI 95% [91.8-100], respectively. The most frequent disease recognised among the HCV negative patients was Sjögren's syndrome (SS) (55/117, 47.0%), and the sensitivity and the specificity of the CV classification criteria were 88.9% CI 95% [76.5-100] and 91.3% CI 95% [79.2-100], respectively. CONCLUSIONS: The classification criteria for CV showed a good performance even in HCV-unrelated patients. A slightly lower specificity was observed for the classification of HCV-unrelated CV, since some clinical manifestations included in the clinical item for the classification criteria occurred more frequently in HCV-negative rather than HCV-positive controls with CWV.
21905010 Heterogeneous nuclear RNPs as targets of autoantibodies in systemic rheumatic diseases. 2012 Jan OBJECTIVE: To investigate the abundance of autoantibodies to heterogeneous nuclear RNPs (hnRNPs) in systemic rheumatic diseases. METHODS: Recombinant human hnRNPs A1, B1, C1, E1, F, Gi, H1, I, K, and P2 were prepared. Antibodies to these antigens were determined by Western blotting and by enzyme-linked immunosorbent assay (ELISA) (for hnRNPs B1, E1, F, and H1) in serum samples obtained from patients with chronic fatigue syndrome (control subjects) and from patients with various connective tissue diseases. RESULTS: Western blotting analysis in 106 control subjects and 298 patients with a connective tissue disease revealed that antibodies to all tested hnRNP antigens, except hnRNP Gi, were significantly more prevalent in patients with Sjögren's syndrome (SS) than in control subjects. The highest reactivity was observed for hnRNPs B1, E1, F, and H1 (reactivity in >45% of patients with SS and in 2.8% of control subjects). Reactivity with hnRNPs B1, E1, F, and H1 was also evaluated by ELISA in 89 control subjects and 228 patients with a connective tissue disease. Reactivity with at least 2 of the 4 tested antigens was observed in 1.1% of control subjects, 16% of patients with systemic lupus erythematosus (SLE), and 18% of patients with SS. Reactivity with at least 3 of the 4 antigens was observed in 0% of the control subjects, 3.2% of patients with SLE, and 15% of patients with SS. CONCLUSION: Several hnRNPs are target antigens in SS. The combined presence of antibodies to several hnRNPs was strongly associated with connective tissue disease in general and with SS in particular.
22734707 Chemometric modeling of 5-Phenylthiophenecarboxylic acid derivatives as anti-rheumatic age 2012 Sep Arthritis involves joint inflammation, synovial proliferation and damage of cartilage. Interleukin-1 undergoes acute and chronic inflammatory mechanisms of arthritis. Non-steroidal anti-inflammatory drugs can produce symptomatic relief but cannot act through mechanisms of arthritis. Diseases modifying anti-rheumatoid drugs reduce the symptoms of arthritis like decrease in pain and disability score, reduction of swollen joints, articular index and serum concentration of acute phage proteins. Recently, some literature references are obtained on molecular modeling of antirheumatic agents. We have tried chemometric modeling through 2D-QSAR studies on a dataset of fifty-one compounds out of which forty-four 5-Phenylthiophenecarboxylic acid derivatives have IL-1 inhibitory activity and forty-six 5-Phenylthiophenecarboxylic acid derivatives have %AIA suppressive activity. The work was done to find out the structural requirements of these anti-rheumatic agents. 2D QSAR models were generated by 2D and 3D descriptors by using multiple linear regression and partial least square method where IL-1 antagonism was considered as the biological activity parameter. Statistically significant models were developed on the training set developed by k-means cluster analysis. Sterimol parameters, electronic interaction at atom number 9, 2D autocorrelation descriptors, information content descriptor, average connectivity index chi-3, radial distribution function, Balaban 3D index and 3D-MoRSE descriptors were found to play crucial roles to modulate IL-1 inhibitory activity. 2D autocorrelation descriptors like Broto-Moreau autocorrelation of topological structure-lag 3 weighted by atomic van der Waals volumes, Geary autocorrelation-lag 7 associated with weighted atomic Sanderson electronegativities and 3D-MoRSE descriptors like 3D-MoRSE-signal 22 related to atomic van der Waals volumes, 3D-MoRSE-signal 28 related to atomic van der Waals volumes and 3D-MoRSE-signal 9 which was unweighted, were found to play important roles to model %AIA suppressive activity.