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ID PMID Title PublicationDate abstract
20722033 The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune disease 2010 Nov OBJECTIVE: To test for associations between non-major histocompatibility complex susceptibility loci previously reported in autoimmune diseases and juvenile idiopathic arthritis (JIA). METHODS: Published autoimmune disease genome-wide association studies were reviewed, and 519 single-nucleotide polymorphisms (SNPs) were selected for association testing. The initial cohort included 809 JIA cases and 3,535 controls of non-Hispanic, European ancestry. Of the SNPs, 257 were successfully genotyped, while 168 were imputed with quality. Based on findings in the initial cohort, replication was sought for 21 SNPs in a second cohort of 1,015 JIA cases and 1,569 controls collected in the US and Germany. For the initial cohort, tests for association were adjusted for potential confounding effects of population structure by including principal components derived from a genome-wide association study as covariates in logistic regression models. Odds ratios (ORs) and 95% confidence intervals were calculated. RESULTS: Testing for association of previously reported autoimmune disease genetic associations in the initial cohort suggested associations with JIA in 13 distinct loci. Of these, 7 were validated in the replication cohort. Meta-analysis results for the replicating loci included PTPN22 (rs6679677 [OR 1.58, P = 1.98 × 10(-12) ], rs2476601 [OR 1.64, P = 1.90 × 10(-13) ], and rs2488457 [OR 1.32, P = 6.74 × 10(-8) ]), PTPN2 (rs1893217 [OR = 1.33, P = 1.60 × 10(-9) ] and rs7234029 [OR 1.35, P = 1.86 × 10(-10) ]), ADAD1-IL2-IL21 (rs17388568 [OR 1.24, P = 1.13 × 10(-6) ] and rs13143866 [OR 0.83, P = 1.95 × 10(-4) ]), STAT4 (rs3821236 [OR = 1.27, P = 2.36 × 10(-6) ] and rs7574865 [OR = 1.31, P = 2.21 × 10(-6) ]), C12orf30 (rs17696736 [OR = 1.19, P = 2.59 × 10(-5) ]), COG6 (rs7993214 [OR = 0.76, P = 1.10 × 10(-5) ]), and ANGPT1 (rs1010824 [OR = 0.79, P = 2.91 × 10(-4) ]). These polymorphisms have been reported in diseases such as rheumatoid arthritis, type 1 diabetes mellitus, Crohn's disease, and multiple sclerosis. CONCLUSION: General susceptibility loci for autoimmunity are shared across diseases, including JIA, suggesting the potential for common therapeutic targets and mechanisms.
19578851 A case of primary Sjögren's syndrome with pulmonary-limited Wegener's granulomatosis. 2010 Jul A 60-year-old woman had a history of dyspnea for 5-6 weeks. The chest radiograph and computed tomography scans revealed bilateral patchy reticulonodular pattern. The patient had positive test results for antineutrophil cytoplasmic antibody against proteinase-3 (c-ANCA), antinuclear antibody and anti-Ro antibody. According to European Study Group on Classification Criteria for Sjögren's Syndrome, the patient was diagnosed as primary Sjögren's syndrome based on the presence of clinical features, positive findings on Schirmer's test and parotis scintigraphy. Lung biopsy obtained by wedge resection showed granulomatous inflammation with extensive multinuclear giant cells involving the lung parenchyma and vascular structures. There was neither upper airway nor renal involvement. Thus, the patient was simultaneously diagnosed as pulmonary-limited Wegener's granulomatosis. With this unique case, we would like to emphasize that the awareness of ANCA-associated vasculitis as a diagnostic possibility in primary Sjögren's syndrome is important during the work-up of lung lesions.
18801600 [Kappa light chain deposition disease, presenting as Sjögren's syndrome, successfully tre 2009 Jan INTRODUCTION: Light chain deposition disease is a systemic disorder characterised by tissue deposition of monoclonal immunoglobulin light chains without tinctorial properties. It has been exceptionally reported with salivary involvement mimicking Sjögren's syndrome and peripheral neuropathy. CASE REPORT: We report a case of light chain deposition disease associated with plasma cell dyscrasia presenting as sicca syndrome with salivary glands hypertrophy and polyneuropathy successfully treated by high dose melphalan and autologous blood stem transplantation. CONCLUSION: Light chain deposition disease should be recognized as an aetiology of sicca syndrome and peripheral neuropathy. Further studies should assess the prevalence of sicca syndrome in light chain deposition disease and better characterise the neurological manifestations.
19363610 Multiple bone fracture due to Fanconi's syndrome in primary Sjögren's syndrome complicate 2009 Dec Abstract A 66-year-old woman showing renal dysfunction with elevated serum alkaline phosphatase and anti-SS-A antibody was admitted. A labial salivary gland biopsy showing infiltration of mononuclear cells and positive anti-SS-A antibody with sicca symptoms led to a diagnosis of primary Sjögren’s syndrome (SS). Fanconi’s syndrome was diagnosed by renal tubular acidosis along with renal glucosuria or aminoaciduria and multiple bone fractures on bone scintigraphy. Typical bilateral pulmonary shadows were confirmed as organizing pneumonia (OP) determined by the analysis of bronchoalveolar lavage fluid and transbronchial lung biopsy. A rare complication of Fanconi’s syndrome with OP in SS is described.
20525739 Salivary chemokine levels in patients with primary Sjogren's syndrome. 2010 Sep OBJECTIVE: The present study aimed to investigate the salivary chemokine levels in patients with primary SS (pSS) and compare them with those in patients with non-SS sicca symptoms or non-sicca controls. METHODS: Unstimulated and stimulated whole saliva samples were obtained from pSS patients (n = 30) and age- and gender-matched patients with non-SS sicca (n = 30) and non-sicca healthy controls (n = 25). Salivary CCL2, CCL3, CCL4, CXCL8 and CXCL10 levels were measured using a Luminex bead-based multiplex assay. RESULTS: Patients with pSS had significantly different distributions of salivary CCL3 (P = 0.0001 by the Kruskal-Wallis test), CCL4 (P < 0.00001), CXLC8 (P < 0.0001) and CXCL10 (P < 0.05) levels in unstimulated saliva and all chemokine levels in stimulated saliva when compared with non-SS sicca and non-sicca controls. In comparison with chemokine production rate, the CXCL8 and CXCL10 production rates were significantly higher in pSS than in non-SS sicca controls (P < 0.01 by the Mann-Whitney test). Logistic regression analyses revealed that salivary CXCL8 (P < 0.05) and CXCL10 (P < 0.05) were the significant discriminating chemokines between the pSS and non-SS sicca groups. Although CXCL8 and CXCL10 levels were not correlated with the focus scores, CXCL8 and CXCL10 levels were significantly associated with salivary gland dysfunction. CONCLUSION: These results support the notion that CXCL8 or CXCL10 chemokine plays a role in the pathogenesis of pSS.
19404125 Rupture of a spinal artery aneurysm attributable to exacerbated Sjögren syndrome: case re 2009 May OBJECTIVE: Presentation of a patient with acute subarachnoid hemorrhage from a ruptured spinal artery aneurysm attributable to exacerbated Sjögren syndrome. CLINICAL PRESENTATION: A 46-year-old woman with symptoms of exacerbated Sjögren syndrome experienced the acute onset of extreme headache accompanied by nuchal rigidity. INTERVENTION: A computed tomographic scan revealed subarachnoid hemorrhage. Angiography showed an isolated aneurysm of a branch of the right vertebral artery that was a feeding artery of the anterior spinal artery. Neither operative clipping nor endovascular coiling of the aneurysm was reasonable, owing to the high risk of occluding the anterior spinal artery during the intervention. Further diagnostic measures confirmed Sjögren syndrome and revealed cryoglobulinemic vasculitis, membranoproliferative glomerulonephritis with acute renal failure, Hashimoto thyroiditis, and acute hydrocephalus. In the course of conservative treatment, the patient recovered completely from the subarachnoid hemorrhage. One year after treatment with glucocorticoids and immunosuppressive agents, both the aneurysm and the vasculitis could no longer be detected on conventional angiography. CONCLUSION: Generally, spinal artery aneurysms are exceptionally rare, and few cases of rupture with subsequent subarachnoid hemorrhage have been published. We report on a ruptured spinal aneurysm attributable to Sjögren syndrome-associated cryoglobulinemic vasculitis. Conservative treatment with glucocorticoids and immunosuppressive agents led to resolution of the vasculitic spinal aneurysm.
19588839 [Estimation of anti-SS-A Ab and anti-SS-B Ab in the serum of Yusho victims]. 2009 May Polychlorinated biphenyls (PCB) causes the release of superoxide during the metabolic process. Therefore, Yusho victims are thought to be exposed to oxidative stress caused by PCB, because high concentrations of PCB are still detected in the serum of Yusho victims. Furthermore, oxidative stress contributes to the generation of autoantibodies because of oxidative modification. In order to estimate the autoantibody in Yusho victims, we mesured serum levels of anti-SS-A antibody (Ab) and anti-SS-B Ab both in certified Yusho victims and age-matched controls. The mean values of anti-SS-A Ab were 4.0 +/- 17.1 (Index) in certified Yusho victims and 0.7 +/- 0.5 (Index) in controls. And the mean values of anti-SS-B Ab were 7.4 +/- 4.6 (Index) in certified Yusho victims and 5.6 +/- 1.7 (Index) in controls. Although the occurrence rates of anti-SS-A Ab and anti-SS-B Ab were high in Yusho victims, there were no significant difference between Yusho victims and controls.
20733192 Role of contrast-enhanced ultrasonography in primary hepatic lymphoma. 2010 Sep OBJECTIVE: Ultrasonography is the first examination performed for screening of hepatocellular carcinoma (HCC); contrast-enhanced ultrasonography (CEUS) can help discriminate between HCC and other lesions. Primary hepatic lymphoma (PHL), even if rare, should be considered in the differential diagnosis of focal liver lesions (FLLs). Few data are available in the literature about the role of CEUS in the diagnosis of PHL; we tried to determine whether CEUS could have a role in this setting. METHODS: we describe 2 cases of primary non-Hodgkin lymphoma of the liver associated with hepatitis B virus (HBV) infection. The first patient was a 62-year-old man who was an HBV-inactive carrier, and the second was a 58-year-old man with type 2 diabetes and chronic HBV hepatitis. RESULTS: in both cases, ultrasonography showed a hypoechoic liver lesion (4 and 3 cm, respectively) with irregular margins in segment 4 of the liver. On CEUS, these lesions were inhomogeneously hyperenhanced in the arterial phase and hypoenhanced in the portal and late phases. Contrast-enhanced computed tomography (CT) in both patients showed slight hyperenhancement in the arterial phase and hypoenhancement in the remaining phases. Needle biopsy showed marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in both patients. CONCLUSIONS: Contrast-enhanced ultrasonography and CT did not help us differentiate PHL from HCC; in fact, in both cases we saw the characteristic findings of primary HCC. Primary hepatic lymphoma is a rare condition, but it should always be considered in the differential diagnosis of FLLs. We stress the important role of liver biopsy when imaging indicates HCC in patients without underlying cirrhosis.
20557871 Tubulointerstitial nephritis with IgM-positive plasmacytoid large lymphocyte infiltration 2010 Jul We report a 38-year-old woman diagnosed with tubulointerstitial nephritis (TIN) on renal biopsy, followed by being diagnosed with primary biliary cirrhosis (PBC) and Sjögren's syndrome (SS). Immunohistochemically, the cellular infiltrates in TIN were mainly composed of small lymphocytes and IgM-positive plasmacytoid large lymphocytes. IgM-positive plasmacytoid large lymphocytes were not identical with, but colocalized with CD3- or CD20-positive lymphocytes. TIN in patients with PBC is very rare and little is known about immunohistochemical characteristics of infiltrating cells in this setting. To our knowledge, this is the first report demonstrating predominant infiltrating of IgM-positive plasmacytoid large lymphocytes in TIN due to PBC and SS.
20453444 Role of immune response to M3 muscarinic acethylcholine receptor in the pathogenesis of Sj 2010 Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of salivary glands, in which CD4(+) T cells are predominant. These infiltrating T cells play a crucial role in the generation of SS. Previous studies showed that autoantibodies and auto-reactive T cells against M3 muscarinic acethylcholine receptor (M3R) were detected in patients with SS. In this study, to reveal the pathological mechanisms underlying immune response against M3R, we tried to induce SS like sialoadenitis. M3R knockout (M3R(-/-)) mice were immunized with murine M3R peptides. Their splenocytes were isolated and transferred into Rag1 knockout (Rag1(-/-)) mice. Mononuclear cells infiltration was detected in salivary glands of Rag1(-/-) mice inoculated splenocytes of M3R(-/-) mice immunized with M3R peptides. Moreover we transferred CD3(+) cells from splenocytes of M3R(-/-) mice immunized with M3R peptides into Rag1(-/-) mice. In their salivary glands, mononuclear infiltration was also detected. These findings suggest that the immune response to M3R plays a crucial role in the generation of SS like sialoadenitis.
19381638 Pulmonary complications in human T-cell lymphotropic virus type 1 carriers with Sjögren's 2009 Dec In this study, we report three cases diagnosed with human T-cell lymphotropic virus type 1 (HTLV-1) and Sjögren’s syndrome (SS) who developed pulmonary complications. Radiologic and pathologic findings were evaluated. Although the histologic diagnosis was considered to be hypersensitivity pneumonitis in case 1, and discordant usual interstitial pneumonia (UIP) in cases 2 and 3, lymphocytic alveolitis was observed in all cases. We also did a literature review and concluded that, although the pathologic diagnosis of pulmonary complications in HTLV-1 carriers with SS may vary, lymphocytic infiltrations are commonly observed.
21448518 Quality of life of hemodialysis patients in a Brazilian Public Hospital in Belém - Pará. 2010 Mar INTRODUCTION: End-stage chronic kidney disease (CKD) requiring dialysis affects the quality of life sometimes more severely than other chronic diseases, such as rheumatoid arthritis, heart failure, coronary artery disease, and chronic obstructive pulmonary disease, exerting a negative effect on the energy and vitality levels, limiting social interactions, and hindering psychic health. OBJECTIVE: To evaluate the quality of life of patients with CKD on hemodialysis in a public Brazilian Amazonian hospital. METHODS: Data were collected through interview based on the Brazilian version of the SF-36 questionnaire. The study was conducted on 50 patients (mean age, 48 ± 16 years; mean hemodialysis time, 3 ± 2.9 years). RESULTS: The most affected domain was role limitations due to physical health, with a mean score of 36 ± 36, and 58% of the patients in the lowest quartile, while mental health and social functioning were relatively preserved, with most patients in the highest quartile. Men obtained poorer scores than women did for role limitations due to physical health and vitality. Age correlated negatively with physical functioning. Patients on hemodialysis for more than one year had better scores in the social functioning domain, with a positive correlation between dialysis time and physical functioning. CONCLUSIONS: The domains assessed were globally impaired in the population studied, especially regarding role limitations due to physical health, suggesting that chronic disease with prolonged treatment has a negative influence on those domains.
21189317 Glia-induced reversible disruption of blood-brain barrier integrity and neuropathological 2011 Jan The blood-brain barrier (BBB) is the regulated interface that mediates selective transcellular transport of nutrients and essential components from the blood into the brain parenchyma. Many neurodegenerative diseases including stroke, multiple sclerosis, rheumatoid arthritis, and AIDS dementia exhibit loss of BBB integrity. Despite the increasing body of evidence for the involvement of glia in maintaining the BBB, few studies have addressed glial/endothelial/extracellular matrix interactions. A chemically induced astrocyte lesion provides a noninvasive model to study reversible BBB dysfunction in vivo. Blood-brain barrier integrity was assessed with fluorescent dextran tracers (3-70 kDa) and magnetic resonance imaging, in parallel with confocal and electron microscopy imaging of the neurovascular unit. These studies demonstrated modified tight-junction protein expression with loss of vascular integrity. We propose that adherens junction proteins and extracellular matrix remodeling provide a temporary size-selective barrier, whereas astrocyte and microglia activation direct tight-junction proteins to paracellular domains and restore BBB integrity. Morphological comparisons were made with the area postrema, a circumventricular organ with a naturally porous BBB. Further studies into cellular mechanisms of glial/endothelial/extracellular matrix interactions may identify novel glial-based therapeutic targets and innovate therapies for modulating diseases in which gliosis and raised levels of pro-inflammatory mediators are central components.
21074639 Excess of autoimmune and chronic inflammatory disorders in patients with lymphoma compared 2011 Feb OBJECTIVE: We investigated the association between autoimmune and chronic inflammatory disorders and several cancer types including lymphomas. METHODS: All cancer patients diagnosed between 1995 and 2007, aged 15 to 90 years, and registered in the Eindhoven Cancer Registry were included in this study. Co-morbidity at diagnosis was recorded by qualified registry personnel who obtained the information from the clinical record. We determined the prevalence of rheumatoid arthritis (RA), chronic inflammatory bowel diseases, connective and vascular tissue diseases, ulcers of the stomach and duodenum, hepatitis, human immunodeficiency virus (HIV), and tuberculosis (TBC) among newly diagnosed patients with lymphoma and compared this with the prevalence among patients with all other cancers. RESULTS: The prevalence of most of these co-morbidities was higher in patients with lymphomas than those with other malignancies. RA was more often present in newly diagnosed patients with most lymphomas, ulcers of stomach and duodenum in patients with marginal zone lymphoma, hepatitis in case of diffuse large B-cell lymphoma, HIV with aggressive B-cell lymphoma, and TBC with mantle cell lymphoma. CONCLUSION: This study confirms the positive association between autoimmune and chronic inflammatory disorders and the various lymphoproliferative malignancies, suggesting either a shared etiology or pathogenesis or a direct causal relation. This is a fairly new method to study aetiological questions about cancers in a population-based cancer registry.
20854696 Does suprascapular nerve block reduce shoulder pain following stroke: a double-blind rando 2010 Sep 21 BACKGROUND: Shoulder pain is a common complication of a stroke which can impede participation in rehabilitation programs and has been associated with poorer outcomes. The evidence base for current medical and therapeutic management options of hemiplegic shoulder pain is limited. This study will evaluate the use of suprascapular nerve block injection as part of an interdisciplinary approach to the treatment of shoulder pain following stroke. The technique has previously been proven safe and effective in the treatment of shoulder pain associated with rheumatoid arthritis and degenerative shoulder conditions but its usefulness in a stroke population is unclear. METHODS/DESIGN: A double blind randomised placebo controlled trial will assess the effect of a suprascapular nerve block compared with placebo in a population of 66 stroke patients. The trial will measure effect of injection on the primary outcome of pain, and secondary outcomes of function and quality of life. Measurements will take place at baseline, and 1, 4 and 12 weeks post intervention. Both groups will continue to receive routine physiotherapy and standard ward care. DISCUSSION: The results of this study could reduce pain symptoms in persons with mechanical shoulder pain post stroke and provide improvement in upper limb function. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12609000621213.
20832998 Regulatory B cells in skin and connective tissue diseases. 2010 Oct While B cells are generally considered to be positive regulators of humoral immune responses due to their ability to differentiate into plasmablasts/plasma cells and produce antibodies, B cells also modulate immune responses through antigen presentation and cytokine secretion. Moreover, "regulatory B cells" that suppress immune responses have been recognized as an important new component of the immune system. In mice, the function of regulatory B cells is almost exclusively dependent on IL-10. The cell-surface phenotype of murine IL-10-producing regulatory B cells is reported to be CD1d(hi)CD5(+) or CD1d(hi)CD21(hi)CD23(+)IgM(hi), and thus their phenotype overlaps with that of CD5(+) B-1a cells, CD1d(hi)CD21(hi)CD23(lo)IgM(hi) marginal zone (MZ) B cells, and CD1d(hi)CD21(hi)CD23(hi)IgM(hi) T2-MZ precursor B cells. Contrary to earlier work that suggested a minor role for B cells in contact hypersensitivity, regulatory B cells are now known to have a critical inhibitory functions in this type of immune response. Furthermore, studies using murine disease models have demonstrated that regulatory B cells play a significant role in autoimmune connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus, as well as organ-specific autoimmune diseases including experimental autoimmune encephalomyelitis and inflammatory bowel disease. In comparison to mouse regulatory B cells, little is known regarding their human counterparts. One recent study demonstrates that human CD19(+)CD24(hi)CD38(hi) B cells possess regulatory capacity. Clarifying the molecular mechanisms by which regulatory B cells suppress immune responses will be of great benefit in the development of new B cell-targeted therapeutic strategies.
20798913 The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neog 2010 Nov Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses.
20711828 [Muscular torticollis]. 2010 May OBJECTIVE: Correction of malalignment of the cervical spine with the head tilted to the side of the shortened muscle and rotation to the opposite side due to a contract sternocleidomastoid muscle. Attainment of an increased range of motion of the cervical spine and a better cosmetic appearance. Regression of a facial asymmetry. INDICATIONS: Contract sternocleidomastoid muscle with deformity intolerable by the patients and their parents. CONTRAINDICATIONS: Bony anomalies with consecutive torticollis. Torticollis caused by other muscular contractures (trapezoid muscle). Torticollis due to acute rheumatoid arthritis or other inflammation around the neck. Other forms of torticollis (psychogenic, ocular, vestibular or spasmodic torticollis). SURGICAL TECHNIQUE: In younger children, subcutaneous tenotomy of the distal part of the sternocleidomastoid muscle. At preschool age, additional incision of the deep cervical fascial layer with an open tenotomy. In delayed operations, open distal and proximal tenotomy together with incision of the deep fascial layer or complete excision of the sternocleidomastoid muscle. POSTOPERATIVE MANAGEMENT: Until the age of 6 years, application of a Minerva cast after surgery for 6 weeks. Subsequently, physical therapy for 6 months. In children of school age and older people, application of a soft cervical bandage for 6 weeks with functional physiotherapy. RESULTS: In 83 reexamined patients with muscular torticollis, 76 biterminal and seven distal tenotomies had been performed. Regarding the age at the time of operation and the interval to follow-up, an improvement of facial symmetry could be achieved. At the control, 25 patients showed complete recovery of facial asymmetry, 43 had a slight and 15 a severe asymmetry. The complication rate was low with one injury to the external jugular vein and one transient facial nerve paresis. In two patients, passive overcorrection in the cast resulted in transient paresis. Two patients developed a recurrence of muscular torticollis.
20695882 The versatility of HDL: a crucial anti-inflammatory regulator. 2010 Dec BACKGROUND: Low levels of plasma high-density lipoprotein (HDL) represent a major cardiovascular risk factor and therefore raising HDL has been proposed to positively affect patients with atherosclerotic heart disease. However, the current evidence that raising HDL per se will reduce atherosclerosis and thereby cardiovascular events still remains controversial. AIMS: In this review, we discuss the diverse anti-atherogenic and anti-inflammatory properties of HDL in the light of recent findings indicating that the quality rather than the mere quantity of HDL determines its beneficial effects against atherosclerosis. More specifically, we will focus on the conspicuous anti-inflammatory properties of HDL as this might contribute to the overall beneficial effects of HDL in diseased patients such as modulation of costimulatory/adhesion molecule expression, cytokine production and inhibition of the prototypical proinflammatory transcription factor NF-κB. RESULTS: A range of clinical disorders share permanent inflammation as a characteristic hallmark including coronary artery disease, chronic kidney disease, diabetes mellitus or rheumatoid arthritis and also display distinct qualitative changes in the HDL compartment. Loss of anti-inflammatory functions of HDL is emerging as an important risk factor for disease progression and survival in these clinical entities. CONCLUSIONS: It will be important to define the anti-inflammatory effects of HDL at the molecular level and to dissect the manifold functional implications to develop both novel functional assays that enable meaningful outcome studies and foster new therapeutic concepts in patients with altered HDL function.
20634382 Vimentin/cardiolipin complex as a new antigenic target of the antiphospholipid syndrome. 2010 Oct 21 Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial and venous thrombosis, recurrent abortions, and antiphospholipid antibodies (aPL). However, it is possible to find patients with clinical signs of APS who persistently test negative for aPL (seronegative APS, or SN-APS). The aim of this study was to identify new antigenic target(s) of autoantibodies in APS patients, which may also be recognized in SN-APS. We tested sera from patients with SN-APS with a proteomic approach by analyzing endothelial cell-surface membrane proteins. Sera from SN-APS patients revealed 2 reactive spots corresponding to vimentin, a protein that is shown to bind cardiolipin in vitro. Antivimentin/cardiolipin antibodies were tested in 29 SN-APS patients, 40 APS patients, 30 patients with systemic lupus erythematosus, 30 with rheumatoid arthritis, 30 with venous or arterial thrombosis, and 32 healthy control patients. We observed that not only a large proportion of SN-APS patients but also almost all the APS patients displayed the presence of antivimentin/cardiolipin antibodies. To verify the possible pathogenic role of these autoantibodies, we demonstrated that affinity-purified antivimentin/cardiolipin antibodies induced interleukin receptor-associated kinase phosphorylation and nuclear factor-κB activation in endothelial cells. Our results prompt to identify vimentin as a "new" cofactor for aPL, which may represent a useful tool mainly in SN-APS patients.