bluuebunny/crossref_metadata_2025 huggingface dataset:
Ankylosing Spondylitis Susceptibility and Severity—Contribution of TNF Gene Promoter Polymorphisms at Positions –238 and –308
Authors: Sousa Elsa , Caetano‐Lopes Joana , Pinto Patrícia , Pimentel Fernando , Teles José , Canhão Helena , Rodrigues Ana , Resende Catarina , Mourão Ana Filipa , Ribeiro Célia , Pinto Teresa Laura , Rosa Carlos Miranda , Da Silva José Alberto Pereira , Branco Jaime , Ventura Francisco , Queiroz Mário Viana , Fonseca João Eurico
Published: September 2009

Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play a central role. The efficacy of TNF blockers has reoriented research in this field in order to explain the influence of TNF in AS pathogenesis. The objective of this study was to access the influence of single nucleotide polymorphisms (SNPs) at positions –308 and –238 of the promoter region of TNF gene on AS susceptibility and prognosis. SNPs were determined by restriction fragment length polymorphisms in patients and controls. AS patients exhibited a decreased frequency of the A allele at position –238 (10%) when compared with controls (18%), suggesting that this could be a protective factor for disease susceptibility. In addition, the –308 GA/AA genotypes were associated with later disease onset in AS patients. These results suggest that TNF gene promoter polymorphisms at positions –238 and –308 could have a small influence on AS susceptibility and prognosis.
Influenza and Autoimmunity
Authors: Toplak Nataša , Avčin Tadej
Published: September 2009

Influenza infection can cause mild to severe illness and can even lead to death. The best way to prevent infection is vaccination against influenza. Complications of influenza infection are not only a consequence of acute infection but can also present as late autoimmune response. Influenza is not frequently implicated as a trigger for autoimmune diseases, but case reports of autoimmune adverse events have been published even following influenza vaccination. In this article we review published data on autoimmune diseases following influenza infection and vaccination. We also discuss immunity of influenza infection in connection to pathogenesis of autoimmune response and autoimmune disease.
Sex Differences in a Murine Model of Sjögren's Syndrome
Authors: Čiháková Daniela , Talor Monica V. , Barin Jobert G. , Baldeviano G. Christian , Fairweather DeLisa , Rose Noel R. , Burek C. Lynne
Published: September 2009

Sex differences in a NOD.H2h4 murine model of Sjögren's syndrome were analyzed. Compared to males, female NOD.H2h4 mice have increased severity of sialoadenitis and have a significantly increased percentage of CD4+ T cells in salivary gland infiltrates. CD4+ T cells in female infiltrates produce more Th2 and Th17 cytokines than in males, while males have greater Th1 responses. Females also have enhanced B cell responses, with higher levels of SSA and SSB serum antibodies, and B cell activation factor F (BAFF). Thus, sex has a strong impact on the severity of murine Sjögren's syndrome by affecting the immune mechanisms driving the autoimmune inflammation.
Infection, Vaccination, and Autoantibodies in Chronic Fatigue Syndrome, Cause or Coincidence?
Authors: Ortega‐Hernandez Oscar‐Danilo , Shoenfeld Yehuda
Published: September 2009

Chronic fatigue syndrome (CFS) is a heterogeneous syndrome of unknown etiology and physiopathology. CFS patients complain about disabling fatigue, depression, difficulty with memory, and concomitant skeletal and muscular pain. Interestingly enough, there is certain overlap between CFS symptoms, autoimmune rheumatic disease, and infectious diseases. Certain neuroendocrine‐immune abnormalities have also been described, and autoantibodies commonly described in some autoimmune diseases have been found in CFS patients as well. An increasing number of autoantibodies, mainly directed against other nuclear cell components, have been illustrated. Likewise, an association between some infectious agents, antibody production, and later CFS onset has been reported. Similarly, vaccination is depicted as playing an important role in CFS onset. Recently, a case report pointed toward a causal association between silicone breast linkage, hepatitis B virus vaccination, and CFS onset in a previous healthy woman. Such findings suggest that there is a likely deregulation of the immune system influenced by specific agents (infections, vaccination, and products, such as silicone). Evidence suggests that CFS is a complex disease in which several risk factors might interact to cause its full expression. Thus, although different alterations have been found in CFS patients, undoubtedly the main feature is central nervous system involvement with immunological alterations. Therefore, a new term neuro‐psycho‐immunology must be quoted. New studies based on this concept are needed in order to investigate syndromes, such as CFS, in which immunological alterations are thought to be associated with concomitant psychological and health disturbances.
Immunizations in Adult Patients with Systemic Sclerosis
Authors: Launay Odile , Guillevin Loic , Mouthon Luc
Published: September 2009

Immunizations are among the most efficient interventions available to prevent infectious diseases. However, there are no specific recommendations regarding vaccination in patients with systemic sclerosis (SSc). The aim of this review is to propose guidelines concerning immunization for patients with SSc. For SSc patients routine vaccine coverage should be assessed, including live vaccines, which are contraindicated after immunosuppressive therapy initiation; immunization against influenza and pneumococcus should be given especially in patients with pulmonary involvement and those receiving immunosuppressive therapy. To limit the risk of vaccine‐preventable disease transmission to SSc patients, immunization of close contacts and healthcare professionals against influenza, measles‐mumps‐rubella, and varicella should be offered routinely. In conclusion, there is potential for serious illness and death in the underimmunization of high‐risk patients, including those with SSc, and every effort should be made to ensure adequate protection through immunization.
High Sensitive Detection of Double‐Stranded DNA Autoantibodies by a Modified Crithidia luciliae Immunofluorescence Test
Authors: Conrad Karsten , Ittenson Annelore , Reinhold Dirk , Fischer Richard , Roggenbuck Dirk , Büttner Thomas , Bosselmann Hans‐Peter , Steinbach Jörg , Schößler Werner
Published: September 2009

Anti‐double‐stranded (ds)DNA antibodies are serological markers of systemic lupus erythematosus (SLE). Of all anti‐dsDNA antibody detection methods, the Crithidia luciliae immunofluorescence test (CLIFT) is thought to have the highest specificity for SLE. However, the clinical application is hampered by the low diagnostic sensitivity. A CLIFT with modified assay buffer (mCLIFT) was developed and compared with conventional CLIFT, using sera from 110 patients with SLE, 89 anti‐dsDNA ELISA‐positive patients with other diseases (non‐SLE group A), 157 non‐SLE patients with undetectable anti‐dsDNA antibodies by ELISA (non‐SLE group B), 77 disease controls (non‐SLE group C), and 50 healthy blood donors. Out of the 110 anti‐dsDNA antibody ELISA‐positive SLE patients, 84 (76.4%) demonstrated a positive kinetoplast staining, using the mCLIFT, compared to only 42.3%, using the conventional CLIFT. The diagnostic specificity of mCLIFT was 100% with healthy blood donors and 98.1% with the non‐SLE group C (anti‐nuclear antibodies negative; no signs or symptoms of an autoimmune disease) included. In the non‐SLE groups A and B with various other autoimmune diseases or symptoms of a possible autoimmune disease, positive mCLIFT results were obtained in 33.7% and 3.2%, respectively. In conclusion, by modification of the assay buffer, a significant increase in sensitivity of the CLIFT could be observed while retaining the high specificity for SLE. Further investigation is required to check whether the CLIFT‐positive non‐SLE patients develop SLE and whether anti‐dsDNA antibodies detected by the mCLIFT represent a pathogenetic and diagnostic subgroup of autoantibodies that may improve the early diagnosis of SLE or SLE‐overlap syndromes.
Rituximab Use in Pediatric Autoimmune Diseases
Authors: Polido‐Pereira Joaquim , Ferreira Daniel , Rodrigues Ana Maria , Nascimento Catarina , Costa Paula , Almeida Margarida , Da Silva José Eduardo Esteves , Simão Carla , Stone Rosário , Ramos Filipa , Neto Adriano , Da Costa José Carlos Teixeira , Melo‐Gomes José , Gomes‐Pedro João , Viana‐Queiroz Mário , Canhão Helena , Fonseca João Eurico
Published: September 2009

Rituximab (RTX) is currently used in many diseases, but its efficacy and safety in juvenile systemic lupus erythematosus (SLEj) is still unknown. In this chapter we present four case reports of children treated with RTX: three SLE and one immune thrombocytopenic purpura (ITP). Two of the three SLEj patients had class IV lupus nephritis (LN) and hematologic manifestations (pancytopenia), both reaching complete recovery of blood counts and improvement of LN with RTX treatment. Our third SLE patient had a severe onset with generalized microangiopathic manifestations in association with antiphospholipid antibodies and has been in remission for almost 1 year after RTX. However, our fourth case, a patient with ITP and renal failure, was treated with RTX without either hematologic or renal response.
Seronegative Autoimmune Diseases
Authors: Alessandri Cristiano , Conti Fabrizio , Conigliaro Paola , Mancini Riccardo , Massaro Laura , Valesini Guido
Published: September 2009

A close relationship exists between autoimmunity and autoantibodies; despite this, some patients are persistently negative for disease‐specific autoantibodies. These conditions have been defined as seronegative autoimmune diseases. Although the prevalence of seronegative autoimmune diseases is low, they may represent a practical problem because they are often difficult cases. There are also situations in which autoantibodies are positive in healthy subjects. In particular, three different conditions can be described: latent autoimmunity, preclinical autoimmunity, and postclinical autoimmunity. Here, we analyze briefly the meaning of autoantibody negativity in the seronegative autoimmune diseases, focusing in particular on the specificities associated with systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis.
Pneumatosis Intestinalis Presenting in Autoimmune Diseases
Authors: Dovrish Zamir , Arnson Yoav , Amital Howard , Zissin Rivka
Published: September 2009

Pneumatosis intestinalis (PI) is an uncommon condition characterized by the presence of gas within the wall of the gastrointestinal tract. PI is a physical or imaging finding that is the result of an underlying pathological process or a disease. This finding may present in diverse conditions, such as obstructive pulmonary disease and intestinal disease, including obstruction, inflammation, or ischemia. PI has also been reported in different autoimmune conditions, especially in systemic sclerosis and rarely with systemic lupus erythematosus. In this report we present PI occurring in three patients with different autoimmune conditions and review the literature.
Autoimmune Thyroid Disease and Autoimmune Rheumatic Disorders
Authors: Lazúrová Ivica , Benhatchi Karim , Rovenský Jozef , Kozáková Darina , Wagnerová Hedviga , Tajtáková Mária , Shoenfeld Yehuda , Macejova Z.
Published: September 2009

Chronic autoimmune thyroiditis (ATD) frequently overlaps with autoimmune rheumatic diseases. The aim of this study was to evaluate the prevalence of various non‐organ‐specific autoantibodies in patients with ATD, as well as the presence of ATD in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Subjects and Methods: Group 1 comprised 80 patients with ATD, and group 2 contained 80 patients with SLE or RA. A control group consisted of 34 healthy subjects. Group 1 was examined for the presence of non‐organ‐specific autoantibodies. Serum fT3, fT4, TSH, and antibodies against thyroglobulin, thyroperoxidase, as well as ultrasound of thyroid gland, were determined in group 2. Results: Patients with ATD had a significantly higher prevalence of antinuclear antibodies (ANA) than control subjects (45% vs. 14.7%, P < 0.001). There were no significant differences in the prevalence of other antibodies between the groups. ANA‐positive patients were younger than ANA‐negative ones and had significantly higher anti‐TG values (P < 0.05). The prevalence of ATD in group 2 was significantly higher than in the control subjects (24% vs. 8%, P < 0.05). No significant differences in the prevalence of ATD were detected between SLE and RA. Conclusion: The authors conclude that ANA is the most frequent non‐organ‐specific antibody associated with ATD, while the other antibodies occur rarely. The prevalence of ATD in SLE and RA patients was 24%. These results indicate that it is clinically important to screen patients with SLE and RA for the coexistence of thyroid autoimmune disease.
An Open‐label Study Adding Creatine Monohydrate to Ongoing Medical Regimens in Patients with the Fibromyalgia Syndrome
Authors: Leader Avi , Amital Daniella , Rubinow Alan , Amital Howard
Published: September 2009

Fibromyalgia is an ill‐defined condition that causes pain and disability but still lacks effective treatment. The aim of this open‐label study was to assess the efficacy of administering a food supplement, creatine monohydrate, in an “add on” to existing therapies in patients with fibromyalgia. This study included 30 patients with fibromyalgia. After 8 weeks of receiving creatine, we witnessed a significant improvement in parameters reflecting severity of fibromyalgia, quality of life and sleep, disability, and pain. These results deteriorated 4 weeks after stopping creatine therapy. The findings of this study are preliminary and limited due to the small sample and relatively high rate of dropouts.
A Dual Role for HSP90 and HSP70 in the Inflammatory Myopathies
Authors: De Paepe Boel , Creus Kim K. , Martin Jean‐Jacques , Weis Joachim , De Bleecker Jan L.
Published: September 2009

Chaperones assist the metamorphosis of polypeptides to fully functional proteins. The family of heat shock proteins 70 (HSP70) bind at an early stage, while the HSP90 bind to proteins near their active conformation. We studied HSP90 and HSP70 in muscle biopsies from controls and patients diagnosed with the three main idiopathic inflammatory myopathies (IIM), namely dermatomyositis (DM), sporadic inclusion body myositis (IBM), and polymyositis (PM). Human skeletal muscle displayed constitutive levels of protein, but in IIM both HSP90 and HSP70 were upregulated. Regenerating muscle fibers of IIM and muscular dystrophy patients showed increased expression of HSP90 and HSP70, as did atrophic perifascicular muscle fibers of DM and vacuolated fibers of IBM. The infiltrates of IIM displayed weak homogeneous HSP70 staining. HSP90 were specifically upregulated in the CD68+ cells, actively invading non‐necrotic muscle fibers of IBM/PM and co‐localized with inducible NO synthase. HSP90:HSP70 ratios were increased in IBM and PM tissues displaying high inflammation grade. Our results point to a multifaceted role for chaperones in muscle tissue: a general protective role for both HSP90 and HSP70 families in damaged muscle fibers, and a specific cytotoxic role for HSP90 in muscle fiber invasion typically associated with IBM and PM.
CXCR3, Inflammation, and Autoimmune Diseases
Authors: Lacotte Stéphanie , Brun Susana , Muller Sylviane , Dumortier Hélène
Published: September 2009

CXCR3 is a G protein–coupled, seven‐transmembrane receptor that binds and is activated by the three IFN‐γ‐inducible chemokines of the CXC family named CXCL9, CXCL10, and CXCL11. These chemokines are not constitutively expressed but are up‐regulated in a proinflammatory cytokine milieu. Consequently, their major function is to selectively recruit immune cells at inflammation sites, but they also play a role in angiogenesis mechanisms. In the last few years, strong experimental and clinical evidence has been obtained supporting the idea that the CXCR3 pathway is involved in the development of autoimmune diseases, especially by creating local amplification loops of inflammation in target organs, thereby inducing worsening of clinical manifestations. This article briefly reviews what we know today about the nature and functions of CXCR3, with special emphasis on its involvement in two main rheumatic systemic autoimmune diseases, namely rheumatoid arthritis and systemic lupus erythematosus.
Statins for the Treatment of Antiphospholipid Syndrome?
Authors: Jajoria Praveen , Murthy Vijaya , Papalardo Elizabeth , Romay‐Penabad Zurina , Gleason Caroline , Pierangeli Silvia S.
Published: September 2009

Fluvastatin has been shown to revert proinflammatory/prothrombotic effects of antiphospholipid antibodies (aPL) in vitro and in mice. Here, we examined whether fluvastatin affects the levels of proinflammatory/prothrombotic markers in antiphospholipid syndrome (APS) patients. Vascular endothelial growth factor (VEGF), soluble tissue factor (sTF), tumor necrosis factor‐α (TNF‐α), soluble intercellular adhesion molecule‐1 (sICAM‐1), sE‐selectin (E‐sel), C‐reactive protein (CRP), and soluble vascular cell adhesion molecule (sVCAM‐1), were measured in the sera of 93 APS patients and 60 controls and in the sera of nine patients with APS before and after 30 days of treatment with fluvastatin. Elevated levels of VEGF, sTF, and TNF‐α were found in APS patients. Fluvastatin significantly reduced those markers in the majority of treated subjects. The data from this study show that statins may be beneficial in aPL‐positive patients and warrant larger clinical trials to confirm the efficacy of the drug for the treatment of APS clinical manifestations.
Celiac G+ Antibody Assay for the Detection of Autoantibodies in Celiac Disease
Authors: Bansal Anil K. , Lindemann Matthew J. , Ramsperger Vince , Kumar Vijay
Published: September 2009

Celiac disease (CD) affects approximately 1% of the population and may present with varied symptomatic as well as asymptomatic clinical manifestations. Simple methods of detecting CD such as serum antibody tests have helped in the early identification of the disease thus preventing serious complications of the disorder. Our objective is to develop specific and sensitive immunoassays that are reliable in the detection of CD. To this end, immunoassays were developed for the detection of IgG and IgA antibodies to gliadin using synthetic peptides. Over 200 serum samples were included in the study from individuals with CD submitted for endomysial (EMA) and tissue transglutaminase (tTG) antibody tests as well as from disease controls and healthy normals. To examine the reliability of the Celiac G+ antibody test in comparison with EMA, a test with higher sensitivity and specificity, samples with low and high EMA titers were included in the study. Comparative evaluations of the Celiac G+ antibody assay were made with EMA and another commercially available gliadin peptide assay along with tTG antibody assays. The data show that as the EMA levels increased the sensitivity of detection of antibodies to synthetic peptides on both systems increased, reaching 100% at EMA titers greater than 160. The diagnostic performance of the newly developed Celiac G+ synthetic gliadin peptide assay is significantly superior in comparison with another available gliadin peptide immunoassay. Overall, the diagnostic performance of the Celiac G+ assay for IgA and IgG reached a sensitivity of 80% and 90% respectively in comparison with EMA. Similar comparison of the EMA positivity to the other available synthetic peptide immunoassay yielded sensitivities of 59% (IgA) and 75% (IgG). The specificity of the Celiac G+ antibody assay for IgA and IgG was 90–95% as compared to the other similar assay with specificity of 88–90%. In conclusion, the performance of the recently developed Celiac G+ ELISA is superior in both its sensitivity and specificity in comparison with other available synthetic gliadin peptide immunoassays. Furthermore, the IgG Celiac G+ antibody test and IgA tTG antibody test used in combination is an excellent screening algorithm for suspected cases of celiac disease.
Distribution of the NF‐κB Complex in the Inflammatory Exudates Characterizing the Idiopathic Inflammatory Myopathies
Authors: Creus Kim K. , De Paepe Boel , Werbrouck Bart F. , Vervaet Veerle , Weis Joachim , De Bleecker Jan L.
Published: September 2009

The transcription factor nuclear factor‐κB (NF‐κB) is a ubiquitously expressed protein family that is considered crucial in autoimmunity. We describe NF‐κB p50 and p65, and the inhibitor I‐κBα in the inflammatory exudates characteristic for the different idiopathic inflammatory myopathies (IIM), that is, endomysial CD8+ cytotoxic T cells invading non‐necrotic fibers in polymyositis (PM) and sporadic inclusion body myositis (sIBM), and the perimysial/perivascular CD20+ B cells and CD4+ T cells in dermatomyositis (DM). We also analyzed other inflammatory cells in the vicinity of active inflammation sites. Strikingly, actively invading CD4+ cells in PM and sIBM contained both p65 and p50, whereas I‐κBα was absent. This could point to a high activation state in which these cells are capable of expressing a variety of inflammatory mediators, contributing to the degradation of non‐necrotic fibers. Secondly, CD68+ macrophages in the infiltrates in all three IIM subtypes showed strong nuclear p50 and I‐κBα staining. This may point to a role for p50 in counteracting inflammation, a reaction that could be enhanced by an upregulation of I‐κBα as we observed with immunofluorescence. These results shed further light on the immunopathology of PM, sIBM and DM. CD4+ and CD68+ mononuclear cells may play a more prominent role than previously assumed.
Vitamin D Metabolites as Clinical Markers in Autoimmune and Chronic Disease
Authors: Blaney Greg P. , Albert Paul J. , Proal Amy D.
Published: September 2009

Recent research has implicated vitamin D deficiency (serum levels of 25‐hydroxyvitamin D <50 nmol/L) with a number of chronic conditions, including autoimmune conditions such as multiple sclerosis, lupus, and psoriasis, and chronic conditions such as osteoporosis, osteoarthritis, metabolic syndrome, fibromyalgia and chronic fatigue syndrome. It has been assumed that low levels of 25‐hydroxyvitamin D (25‐D) accurately indicate vitamin D storage and vitamin D receptor (VDR)–mediated control of calcium metabolism and innate immunity. To evaluate this assumption, 25‐D and 1,25‐dihydroxyvitamin D3 (1,25‐D) levels were measured in 100 Canadian patients with these conditions. Additionally, other inflammatory markers (CK, CRP) were measured. Results showed a strong positive association between these autoimmune conditions and levels of 1,25‐D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25‐D are a sensitive measure of the autoimmune disease state. Rather, these findings support the use of 1,25‐D as a clinical marker in autoimmune conditions. High levels of 1,25‐D may result when dysregulation of the VDR by bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25‐D in a normal range.
A Fusion Protein Composed of IL‐2 and Caspase‐3 Ameliorates the Outcome of Experimental Inflammatory Colitis
Authors: Sagiv Yuval , Kaminitz Ayelet , Lorberboum‐Galski Haya , Askenasy Nadir , Yarkoni Shai
Published: September 2009

Targeted depletion of immune cells expressing the interleukin‐2 (IL‐2) receptor can exacerbate inflammatory bowel disease (IBD) through elimination of regulatory T (Treg) cells, or ameliorate its course by depletion of cytotoxic cells. To answer this question we used a fusion protein composed of IL‐2 and caspase‐3 (IL2‐cas) in an experimental model of DSS‐induced toxic colitis. In a preventive setting, co‐administration of DSS with a daily therapeutic dose of IL2‐cas for seven days improved all disease parameters. Although CD4+CD25+ T cells were depleted in the mesenteric lymph nodes, a fractional increase in CD4+FoxP3+ T cells was observed in the spleen. Likewise, IL2‐cas therapy improved the outcome of established disease in a chronic model of colitis. These data demonstrate that therapies that use IL‐2 as a targeting moiety exert a protective effect over the colon under conditions of inflammation. The efficacy of IL‐2–targeted therapy is attributed to reduced activity of reactive T cells, which ameliorates the secondary inflammatory infiltration. IL2‐cas evolves as a potential therapeutic tool in IBD.
A New Year in Autoimmunity
Authors: Selmi Carlo
Published: September 2009

Over the past year there have been several new developments in our understanding of autoimmunity, as well represented by several lines of evidence obtained from basic, translational, and clinical research alike. To summarize novel findings reported in 2008 this article will review selected publications from the most prominent scientific journals and ultimately suggest some links in the field of autoimmune diseases from leading journals dedicated to autoimmunity. The take‐home message from these readings is that autoimmunity ultimately becomes a uniform scenario in which similarities between conditions significantly outnumber differences in terms of pathogenesis and mechanisms.
Microparticles and the Hygiene Hypothesis
Authors: Martín Pablo I. , Sánchez Pablo Alejandro , Rewald Enrique
Published: September 2009

Departing from the functional parallelism that undoubtedly exists between the nervous and immune system, we suggest that the latter also counts with means for information exchange that may result in a mutual influence of immune processes between nearby individuals. Our concept relies on a molecular interface that is composed and, at the same time, interfered or modulated by the vast number of environmental agents from the surrounding milieu. We highlight the possibility that microparticles, previously shown to act as mediators of the transfer of receptors and other relevant immune molecules between distant cells, may represent a minor immune medium. In line with this argument, we envisage a potential role for the suggested interindividual immune link particularly in marginal conditions, such as those that shaped life in historical population centers or even in currently undeveloped countries. We speculate that overcrowding and unhygienic habits as dominant conditions may provide a suitable framework for the interconnection of individuals by means of their respective body wrapping microenvironments. As a corollary, we propose that collective means of defense may belong to the toolbox with which the immune system faces exceptional challenges. In the context, it seems highly suggestive to establish a link with the hygiene hypothesis. In this scenario, modern lifestyle appears as an interfering factor by dismantling the necessary conditions for the emergence of the immunological interface. Therefore, it is not implausible to confer to this modern ‘immunological miscommunication’ a role in current trends concerning the incidence of autoimmunity, allergy and chronic inflammation.
Prevention of corneal graft rejection
Authors: PLEYER U
Published: September 2009

Abstract not provided
Interferon‐alpha for uveitis
Authors: BODAGHI B , DICK AD
Published: September 2009

Abstract not provided
Final results of European Remicade? RESCU study
Authors: DE SMET M
Published: September 2009

Abstract not provided
Adalimumab (Humira®) therapy for uveitis
Authors: NERI P
Published: September 2009

Purpose To review the current Literature and to describe the experience of a tertiary referral centre on Adalimumab (Humira®) therapy for uveitis.

Methods The current literature is reviewed and the experience of a tertiary referral centre is reported.

Results Chronic non‐infectious uveitis (NU) remains one of the most challenging problems in ophthalmology. Often, early and aggressive treatment is needed for a good visual acuity outcome. Local and oral corticosteroids remain the first line of treatment, even though side effects, such as glaucoma, cataract and Cushing Syndrome, can be serious and not tolerable. Therefore, a variety of immunosuppressive agents are in use, such as Cyclophosphamide, Methotrexate, Cyclosporin A, Azathioprine and Mycophenolate mofetil. Recently, new types of drugs, called “biologic agents”, are available. In the model of experimental autoimmuneuveitis (EAU) it has been demonstrated that tumor necrosis factor‐alpha (TNF‐α) may play a key role in uveitis. Beside other anti‐ TNF‐α drugs, Adalimumab (Humira®) is the newest biologic drug available. Adalimumab is a recombinant human IgG1 monoclonal antibody to TNF‐α that blocks the TNF‐α biologic activity. Adalimumab seems to control uveitis unresponsive to the traditional immunosuppressive agents and, moreover, its subcutaneous administration makes the procedure easier.

Conclusion The data in the literature suggest that Adalimumab can be an effective and safe therapy for the uveitis, by controlling inflammation of the eye. The duration of treatment have still to be investigated in larger studies and further trials are mandatory to validate the preliminary data.
Age related macular degeneration
Authors: VOIGT M
Published: September 2009

Abstract not provided
Retinal dystrophies
Authors: HAWLINA M
Published: September 2009

Purpose Review of typical clinical pictures and gene defects associated with most prevalent retinal dystrophies such as retinitis pigmentosa, Stargardt's macular dystrophy, Best's macular dystrophy, cone dystrophy, congenital stationary night blindness, pattern dystrophy and some rarer types of dystrophies.

Methods Clinical methodology to diagnose retinal dystrophies is based on conventional perimetry, microperimetry, autofluorescence imaging, OCT and electrophysiology. The use of these methods will be outlined in characteristic cases. Genetic testing is necessary to characterise the genetic cause of these diseases as clinical heterogeneity is large.

Results Autofluorescence imaging and OCT non‐invasively reveal typical morphological patterns of different retinal dystrophies, for which fluorescein angiography is not necessary. Different electrophysiological methods (photopic/scotopic ERG, pattern ERG, multifocal ERG, visual evoked potentials) determine function of retinal layers and the macula. Residual retinal function and progression of the disease can thus be objectively assessed and followed‐up. In initial stages when retinal changes may not be visible, electrophysiological features can reveal the site of dysfunction and dissociate it form putative optic nerve disease.

Conclusion The residents should be aware of the differential diagnosis of retinal dystropies and be able to dissociate between them. Also, typical genetic transmission and genetic counseling is important for the information that is given to the patient. Residents should be aware of treatable associated features of retinal dystrophies such as cataract or cystoid macular edema or glaucoma.
Refraction and refractive surgery
Authors: COCHENER B
Published: September 2009

Abstract not provided
Fungal infections
Authors: KESTELYN P
Published: September 2009

Abstract not provided
Retinal detachment in phakic patients
Authors: CHIQUET C
Published: September 2009

Purpose this review aims to summarize risk factors, preoperative evaluation and principles of operative methods of retinal detachment of phakic eyes

Methods Preoperative evaluation includes detailed examination of the retina, the identification of retinal breaks and classification of proliferative retinopathy. Main operative methods will be presented with ab externo or ab interno techniques.

Results after a detailed characterization of the retinal detachment, the more appropriate surgical methods will be explained for the search, the treatment (laser or cryotherapy), closure (scleral buckling materials) of retinal breaks, management of subretinal fluid (drainage) and the choice of the intraocular tamponnade (gas or silicone).

Conclusion this review will discuss the main advantages of each surgical technique and examples of management will be presented (simple phakic detachment, associated cataract, giant tears, high myopia).
Primary vitrectomy in retinal detachment: is scleral buckling still indicated?
Authors: POURNARAS CJ
Published: September 2009

Purpose The surgical management of rhegmatogenous retinal detachment has evolved due to introduction of primary pars plana vitrectomy (PPV). The choice of primary vitrectomy has grown over recent years even for managment of simple retinal detachment.

Methods Review of reports on primary vitrectomy treatment for rhegmatogenous uncomplicated retinal detachment. Evaluation of optimal indications of vitreectomy for specific types of retinal detachments.

Results Comparaison of primary vitrectomy with scleral buckling had failed to demonstrate advantage of this method regarding anatomical and functional results. Vitrectomy avoids some of the complications associated with scleral buckling, such as diplopia, choroidal detachment, perforation of the sclera, abnormalities in the eyelid, but it carries higher risks of several other complications,including cataract formation in phakic eyes, glaucoma and other problems with tamponade, and new retinal breaks. Data from case series and randomized studies suggest that primary detachments in phakic eyes may be treated successfully with scleral buckling or vitrectomy, whereas vitrectomy appears to be preferable for corresponding detachments in pseudophakic eyes.

Conclusion The choice of primary PPV in new uncomplicated retinal detachment remains to the surgeon's discretion and skills due to lack of controlled randomized trials covering the large spectrum of the retinal detachment pathology.
Retinal detachment after ocular trauma
Authors: JONAS JB
Published: September 2009

Purpose To discuss the clinical characteristics and treatmentoptions for retinal detachment after ocular trauma

Methods The various types of ocular trauma and the different types of retinal detachments occurring as a complication of ocular trauma will be presented and comapred with each other

Results The surgical treatment options for retinal detachment after ocular trauma will be presented.

Conclusion Due to the high variability of ocular traumata and the reulting high high variability in the type and extent of retinal detachments after ocular traumata, the decision on the type of surgical treatment will usually be rather indivudual according to the special clincal situation.
Retinal detachment after uveitis
Authors: DE SMET M
Published: September 2009

Abstract not provided
Orbital tumours
Authors: PRAUSE JU
Published: September 2009

Purpose To give an overview of orbital tumours enabeling the course participants to deal with patients suffering from such tumours.

Methods Schematic demonstration of the flow of clinical symptoms and tests. Discussion of the result of the tests. At the end of the presentation a series of cases illustrate the key points of the lecture
Comparison of the corneal thickness measured by anterior segment optical coherence tomography and specular microscope versus ultrasound pachymetry
Authors: KRUKONYTE R , GALGAUSKAS S , JUODKAITE G , PAJAUJIS M , GARLAITE O , ASOKLIS R
Published: September 2009

Purpose To compare measurements of central corneal thickness (CCT) between the noncontact and contact ultrasound pachymetry and to define endothelial cells density in normal eyes.

Methods 60 eyes of 30 clinically healthy persons – 20 women and 10 men, whose age ranged from 22 to 26 years, were studied. Measurements were performed by specular microscope, anterior segment optical coherence tomography and ultrasound pachymetry. Results obtained with these devices were compared. For statistical analysis of Pearson correlation coefficient and Bland‐Altman plot was used MedCalc software, version 8.1.

Results The mean central corneal thickness (CCT) as measured by CP was 544.9 ± 43.2µm of the right eye and 544.7 ± 41.1µm of the left eye. The mean CCT as measured by OCT was 544.2± 42.1µm of the right eye and 549.50 ± 44.5µm of the left eye. The mean CCT as measured by SM was 558.87± 45.8µm of the right eye and 556.93 ± 45.6µm of the left eye. Pearson correlation coefficient was statistically significant (0.919 ‐ 0.964) for all compared groups. By Bland‐Altman plot method statistically significant deviation was not found for any set of groups. The mean endothelial cell density was 2917.3 ± 532.1 cell/mm² for the right and 2947.6 ± 331.5 cell/mm² for the left eye respectively.

Conclusion 1.The results of central corneal thickness measurements obtained using all three methods are in linear dependence. 2. The intrasession variation of central corneal thickness measured by specular microscope was higher than that of contact method and Visante OCT.
Trabecular meshwork contribution to the uveoscleral outflow
Authors: KARLOVA E , ZOLOTARYOV A , NIKOLAYEVA G
Published: September 2009

Purpose To specify the anterior chamber source of uveoscleral outflow pathway.

Methods We performed perfusion of human cadaver eyes with India ink suspension through clear corneal tunnel. Lamellar scleral dissection revealed the ciliary muscle surface. We observed the character and volume of suprachoroidal fluid. After formaldehyde fixation we performed further dissection of trabecular meshwork and ciliary muscle with subsequent preparation of flat specimens of different layers of trabecular meshwork as well as histological sections for light microscopy.

Results Voluminous flow of India inc‐stained fluid was observed after the ciliary muscle exposure. No unintended damage of the anterior chamber structures or choroid was found. Histological research revealed numerous ink particles in the trabecular meshwork and between the ciliary muscle bundles. The ink particles go from the anterior chamber to the Schlemm’s canal and particularly retain at the scleral spur. The main stream goes along the trabecular beams of uveal layers (2‐nd and 3‐rd of 4 trabecular meshwork layers), bypass the scleral spur and flows into the ciliary muscle. No inc particles were found in the iris root.

Conclusion As the uveal trabeculae continue directly into the clilary muscle bundles, the intertrabecular slits naturally continue into the spaces between the bundles of ciliary muscle. These slits may represent sufficient pathway for uveoscleral outflow. In the sclero‐uveal layer aqueous humor can flow towards the ciliary muscle down to the scleral spur but not beyond. In the uveal layer the fluid can freely pass into radial portion of ciliary muscle. The other structures of the anterior segment appear to play no substantial role in the aqueous outflow.
Assessing macular edema‐ prognostic parameters by OCT
Authors: DE SMET M
Published: September 2009

Abstract not provided
Retinal ganglion cells in culture induced to die by insults of hydrogen peroxide (H2O2), rotenone and glutamate/buthionine sulfoximine (GB) are differentially protected by the flavonoids, epicatechin gallate (EG) epigallocatechin gallate (EGCG) and g
Authors: TENGKU KAMALDEN TA , OSBORNE NN
Published: September 2009

Purpose To investigate the neuroprotective properties of three different flavonoids.

Methods : Immortalized retinal ganglion cells (RGC‐5 cells) in culture were exposed H2O2, rotenone or GB in the presence or absence of EG, EGCG or genistein and cultures analysed by viability assays, immunocytochemistry, western blot, stimulation of reactive oxygen species (ROS) and for histological evidence for apoptosis.

Results Insults of H2O2, rotenone and GB resulted in a time and dose‐dependent stimulation of ROS associated with an apoptotic type of cell death of RGC‐5 cells. Importantly, EG blunted these effects significantly but genistein was ineffective. In contrast, EGCG attenuated these affects only for insults induced by H2O2 and rotenone and not by GB.

Conclusion The results suggest the idea that defined insults can be attenuated by specific flavonoids.
Regulation of retinal ganglion cell gene expression by bHLH transcription factors in the developing and ischemic retinas
Authors: MATTER JM , CHIODINI F , DELAFOSSE L , MATTER‐SADZINSKI L , POURNARAS CJ
Published: September 2009

Purpose The loss of retinal ganglion cells (RGC) in the glaucomatous retina exhibits similarities to the pattern of neuronal degeneration detected after experimental ischemia. However, a short episode of retinal ischemia does not provoke damage but rather triggers an endogenous form of neuroprotection. HIFs are bHLH proteins that regulate hypoxic response in ischemic retinas and they are involved in neuroprotection. Hypoxic environments also occur in the developing embryo and create specific niches controlling cell differentiation. Genetic analyses of HIF functions have revealed the importance of oxygen as a key regulator of ontogeny. We have compared the transcriptomes of RGCs in ischemic versus developing retinas.

Methods Genome‐wide screens were conducted to identify genes which are expressed in newborn RGCs and growing optic nerve axons and which are up‐ or down‐regulated after venal occlusion by photodynamic thrombosis in the rat retinas.

Results Atoh7 is a bHLH protein which is central to the transcriptional network regulating the production of RGCs. Among the targets of Atoh7 there are genes involved in the general metabolism and energy supply – e.g., alpha‐enolase (ENO1), glucose‐6 ‐phosphate isomerase (GPI). These glycolytic enzymes are also targets of HIFs and they are upregulated during hypoxia. To investigate the linkage of glycolysis and mitochondrial activity in RGCs, we monitored by confocal time‐lapse imaging the dynamic distribution of mitochondria in the cell bodies and axons of RGCs that express HIF/Atoh7 targets in developing and ischemic retinas.

Conclusion Some gene expression programs involved in differentiating RGCs might be reinitiated in neuroprotection.
Gene therapy mediates cone rescue and rejuvenation in the R91W mutant form of Rpe65‐deficiency mice
Authors: ARSENIJEVIC Y , CRIPPA S , PIGNAT V , SAMARDZIJA M , KOSTIC C
Published: September 2009

Purpose Given the advances of gene therapy studies to cure RPE65‐derived Leber Congenital Amaurosis (LCA) (clinical trials phase I), it is of prime importance to examine how cones can be rescued in different mutant contexts. Consequently, we evaluated the effect on retinal activity and cone survival of lentivirus‐mediated gene therapy in the R91W knock‐in mouse model expressing the mutant Rpe65R91W gene.

Methods An HIV‐1‐derived lentiviral vector (LV) expressing either the GFP or the mouse Rpe65 cDNA under the control of a 0.8 kb fragment of the human Rpe65 promoter (R0.8) was produced. LV‐R0.8‐RPE65 or GFP was injected into 5‐days‐old (P5) or 1 month‐old R91W mice. Functional and morphological retinal rescues were investigated at 4 months of age.

Results Increased light sensitivity was detected by ERG and pupillary light responses in animals injected with LV‐R0.8‐RPE65 at both P5 and 1 month compared to controls. Histological analysis showed improved expression of cone markers and cone outersegment morphology. Furthermore, the density of cones in the region of RPE65 delivery after treatment at P5 reached the wild type level. However, before injection at 1 month of age, only a fraction of the cones (40% of the number found in WT animals) in the Rpe65R91W/R91W mice expressed cone transducin, this fraction increased to 64% after treatment. Moreover, these cones appeared normal.

Conclusion We show that lentivirus‐mediated Rpe65 gene transfer is very efficacious in early treatments and still efficient during the course of cone degeneration. Moreover, the treatment at 1 month shows a rejuvenation process of the diseased cones. Thus patient suffering from R91W mutation might benefit from a prolonged therapeutic window.
LOC387715/ARMS2 studies – gene sequencing as a procedure of choice
Authors: WYLEGALA E , TEPER S , NOWINSKA A
Published: September 2009

Purpose To search for important mutations in LOC387715/ARMS2 gene.

Methods 80 patients with choroidal neovascularization subsequent to age‐related macular degeneration undergoing anti‐VEGF treatment were screened for LOC387715/ARMS2 mutations. PCR followed by gene sequencing was performed. If polymorphism A69S coexisted with R38STOP gene cloning with pGEM‐T vector was done.

Results R38STOP mutation was found in 5 patients, A69S in 59 patients, in 3 cases R38STOP coexisted with A69S on the other allele. Due to substantial shortening of the R38STOP translation product, the protein is probably not effective. In patients with A69S polymorphism coexisting with R38STOP there is only A69S effective allele – so patients should be treated as A69S homozygous.

Conclusion There is increasing number of studies with A69S variant of ARMS2 but only gene sequencing provide reliable date in these cases. If R38STOP is taken into account, A69S is even more important AMD risk factor. Gene sequencing is advisable in studies with LOC387715/ARMS2.
HSP70 and p62/SQSTM 1 regulate differently autophagy clearance in ARPE‐19 cells
Authors: VIIRI J , HYTTINEN J , RYHäNEN T , SALMINEN A , KAARNIRANTA K
Published: September 2009

Purpose Prior to proteolysis, heat shock proteins (HSPs) attempt to refold misfolded proteins. If this process is not successful proteins are degradated in proteasomes or in lysosomes. In the present study, the roles of the HSP70 and the p62/SQSTM 1 in autophagy clearance were evaluated in ARPE‐19 cells after proteasome inhibitor treatment.

Methods The HSP70, p62/SQSTM 1 and ubiquitin localization were analyzed by immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to analyze the morphological changes. HSP70 and p62/SQSTM 1 levels were modulated using RNA interference techniques. Cell viability was measured by colorimetric assay.

Results The proteasome inhibitor MG‐132 evoked the accumulation of perinuclear aggregates positive for HSP70, p62/SQSTM 1 and ubiquitin‐protein conjugates. We observed that the aggregation was reversible: a cessation of proteasome inhibition led to clearance of the deposits via autophagy. Interestingly, p62/SQSTM 1 mRNA depletion delayed autophagy clearance and significantly increased cell death in conjunction with proteasome inhibition. The hsp70 RNA interference did not change autophagy clearance, but increased cell death in response to proteasome inhibition.

Conclusion The HSP70 and p62/SQSTM 1 regulate differently autophagy clearance in RPE cells. Autophagy seems to be an important mechanism to clean proteasome inhibitor –induced protein aggregates.