Rheumatoid Arthritis: Jonsson R

Delaleu N, Jonsson R. · No affiliation provided · Arthritis Res Ther. · Pubmed #18710591 links to  free full text

Abstract: Sjögren's syndrome is a rheumatic disease in which the salivary and lacrimal glands are the principal targets of a pathological autoimmune reaction. Previous studies in mice indicated that delayed organogenesis and aberrant cell physiology followed by an increase in acinar cell apoptosis precede chronic focal inflammation in the salivary glands and the manifestation of impaired exocrine gland secretion. In a recent study by Wildenberg and colleagues, the authors report aberrant proteolytic activity in the salivary glands of non-obese diabetic mice and the generation of a unique organ-specific 17 kDa fragment of the chemokine and adhesion molecule fractalkine.

Jonsson R, Haga HJ, Gordon TP. · · Scand J Rheumatol. · Pubmed #11132201 No free full text.

Abstract: Sjögren's syndrome is a chronic autoimmune and rheumatic disorder. Most patients have mild to moderate complaints and this may explain the great discrepancy in prevalence found in population studies compared to studies performed in the clinic. However, there is no straightforward and simple diagnostic test for Sjögren's syndrome, although several classification criteria have been designed. Initiatives have been taken to propose a new set of classification criteria in a joint effort by research groups in Europe and USA. A large number of autoantibodies have been reported in Sjögren's syndrome where, in some cases, the antibodies are correlated with the extent and severity of disease. The finding of serum autoantibodies directed against the muscarinic M3 receptor is an important advance in understanding the pathogenesis of not only the impaired glandular function but also associated features of autonomic dysfunction in some patients. The treatment of primary Sjögren's syndrome is still mainly symptomatic.

Isaksen K, Jonsson R, Omdal R. · Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway. · Scand J Immunol. · Pubmed #19000095 No free full text.

Abstract: We performed a search for publications on rituximab (Rtx) in the treatment of primary Sjögren's syndrome (pSS), and assessed the reports for the efficacy of the drug on complaints like sicca symptoms, systemic manifestations and pSS associated lymphoma. We also reviewed the effects on laboratory parameters and potential adverse effects. From the published literature there is little evidence supporting Rtx to have an effect on sicca symptoms, and there is particularly lack of objective improvements in measures of oral and ocular dryness. Systemic manifestations such as fatigue, synovitis, arthralgia, cryoglobulinaemia-related vasculitis, neurological, renal and pulmonary involvement all seem to react favourably to Rtx treatment. The effect on pSS associated non-Hodgkin's lymphoma is also beneficial. Rheumatoid factor concentration is decreasing during Rtx treatment. The levels of anti-SSA and -SSB antibodies are, however, unaltered according to the majority of the studies. The most common complications to Rtx treatment are mild and transient infusion related reactions. Delayed moderate-to-severe reactions are less common, and occur mostly in patients who develop human anti-chimeric antibodies. In conclusion, Rtx is a promising treatment option for severe pSS with systemic complications, but more data from randomized controlled trials are warranted before conclusions on the drug's role can be made with more accuracy.

Delaleu N, Jonsson MV, Appel S, Jonsson R. · Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Haukelandsveien 28, Bergen 5021, Norway. · Rheum Dis Clin North Am. · Pubmed #18984407 No free full text.

Abstract: Sjögren's syndrome (SS) is a rheumatic disease in which the salivary and lacrimal glands are the principal targets of a pathologic autoimmune reaction. SS is manifested by xerostemia and keratoconjunctivitis sicca and marked by persistent focal mononuclear cell infiltration within the salivary glands, often accompanied by glandular atrophy and fibrosis. A challenge is to clarify the roles of genetic backgrounds and environmental trigger. Advanced bioanalytic platforms have enabled identification of potential biomarkers with the intent to improve diagnosis, promote development of prognostic tools, and identify processes for therapeutic treatment. Such approaches allow a glimpse at the apparent complexity of SS.

Szodoray P, Nakken B, Gaal J, Jonsson R, Szegedi A, Zold E, Szegedi G, Brun JG, Gesztelyi R, Zeher M, Bodolay E. · Division of Clinical Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. · Scand J Immunol. · Pubmed #18510590 No free full text.

Abstract: Vitamin D, besides having well-known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune-homeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune-regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases.

Jonsson MV, Delaleu N, Jonsson R. · Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Armauer Hansen Building, 5021, Bergen, Norway. · Clin Rev Allergy Immunol. · Pubmed #17992588 No free full text.

Abstract: Sjögren's syndrome is an autoimmune, chronic inflammatory disease characterized by focal mononuclear cell infiltration of exocrine tissues, accompanied by loss of secretory function. The pathogenesis of autoimmune diseases is complex and, therefore, difficult to study in vitro. As of today, the role of initiating factors remains obscure, clinical symptoms develop late, and there are no tests for early diagnosis of SS. Hence, the disease is difficult to detect and treat. Animal models may provide insights into the identification of target antigens, narrowing the relevant pathological immune mechanisms, and to study the evolution of tissue pathology. This review summarizes current knowledge on murine strains, both spontaneous and induced models, used to study Sjögren's syndrome. Special attention is paid to the characteristics of different strains regarding their properties to mimic specific aspects or stages of the disease.

Haldorsen K, Moen K, Jacobsen H, Jonsson R, Brun JG. · Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Armauer Hansen Building, Haukelandsveien 28, N-5021 Bergen, Norway. · Ann Rheum Dis. · Pubmed #17962240 No free full text.

Abstract: OBJECTIVES: Few studies have addressed the natural course of, or prognostic factors for the salivary and lacrimal function in primary Sjögren syndrome (SS). Except for the early stages, glandular function has been seemingly stable, and SS A antigen (SSA) seropositivity and hypocomplementemia may predict a decline in the van Bijsterveld score. The aim of the present study was to assess the natural course of the exocrine function in a larger cohort based on the American-European consensus criteria for SS, and to address possible predictive factors for a declining exocrine function. METHODS: We performed a retrospective cohort study. A total of 141 patients were investigated with the Schirmer I test and unstimulated whole saliva (UWS). Historical data regarding these tests and focus score were collected from the files of 111 patients. Median time from diagnosis to follow-up investigation was 5.0 years. RESULTS: Median UWS was unchanged during follow-up. Median Schirmer I test improved from 5.0 to 7.0 mm/5 min (p<0.05). Present Schirmer I test was associated with historical high IgG and IgA, positive SSA and SS B antigen (SSB) tests and high focus score, and present UWS with historical low C3/C4. Logistic regression identified high focus scores (odds ratio (OR) = 1.343), and low UWS (OR = 0.692) as factors predicting a 30% or more worsening of the Schirmer I test. High focus scores (OR = 1.488) predicted a 30% or more worsening of the UWS. CONCLUSION: We confirmed previous studies showing a stable or slightly improved exocrine function over time. High focus scores and low UWS were identified as independent predictors of a worsened exocrine function.

Jonsson R, Bolstad AI, Brokstad KA, Brun JG. · Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway. · Ann N Y Acad Sci. · Pubmed #17894008 No free full text.

Abstract: Primary Sjögren's syndrome is a complex autoimmune disorder, considered to represent an ideal disease with which to study the mechanisms underlying autoimmunity because its manifestations are both organ specific and systemic in nature. The characteristic histologic finding in target organs is a progressive focal infiltration of mononuclear lymphoid cells, replacing glandular epithelium (lymphoepithelial lesion). This involvement has been re-emphasized in the 2002 revised EU criteria for Sjögren's syndrome. Moreover, ectopic secondary lymphoid follicles in Sjögren's syndrome contain all elements of relevance for driving an autoimmune response. A number of cytokines and chemokines are involved and particularly B cell activating factor seems to direct the lifespan of infiltrating B cells by enhancing their proliferation and maturation. The recent discovery of clinical benefit after B cell depletion also highlights the pivotal role of B cells in Sjögren's syndrome. A major challenge in Sjögren's syndrome will be to stratify the disease process including genetic and environmental triggers. Identification of novel genetic and molecular markers may lead to the development of better diagnostic and prognostic tools in Sjögren's syndrome including its systemic complications. This minor review will cover the current knowledge on classification, pathogenesis, multiplex findings, potential candidate genes, gene profiling results, and novel therapy approaches. New hypotheses behind the complexity of Sjögren's syndrome are expected to follow.

von Bültzingslöwen I, Sollecito TP, Fox PC, Daniels T, Jonsson R, Lockhart PB, Wray D, Brennan MT, Carrozzo M, Gandera B, Fujibayashi T, Navazesh M, Rhodus NL, Schiødt M. · Department of Oral Medicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. <> · Oral Surg Oral Med Oral Pathol Oral Radiol Endod. · Pubmed #17379156 No free full text.

Abstract: OBJECTIVES: The objective of this study was to identify systemic diseases associated with hyposalivation and xerostomia and develop evidence-based management recommendations for hyposalivation/xerostomia. STUDY DESIGN: Literature searches covered the English language medical literature from 1966 to 2005. An evidence-based review process was applied to management studies published from 2002 to 2005. RESULTS: Several systemic diseases were identified. From studies published 2002 to 2005, 15 were identified as high-quality studies and were used to support management recommendations: pilocarpine and cevimeline are recommended for treating hyposalivation and xerostomia in primary and secondary Sjögren's syndrome (SS). IFN-alpha lozenges may enhance saliva flow in primary SS patients. Anti-TNF-alpha agents, such as infliximab or etanercept, are not recommended to treat hyposalivation in SS. Dehydroepiandrosterone is not recommended to relieve hyposalivation or xerostomia in primary SS. There was not enough evidence to support any recommendations for the use of local stimulants, lubricants, and protectants for hyposalivation/xerostomia. However, professional judgment and patient preferences may support the use of a specific product for an individual patient. CONCLUSIONS: These evidence-based management recommendations should guide the clinician's management decisions for patients with salivary dysfunction related to systemic disease. Future treatment strategies may include new formulations of existing drugs, e.g., local application of pilocarpine. Recent discoveries on gene expression and a better understanding of the etiopathogenesis of SS may open new treatment options in the future.

Jonsson R, Nginamau E, Szyszko E, Brokstad KA. · Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway. · Front Biosci. · Pubmed #17127453 No free full text.

Abstract: The classical view of B cell biology is that these cells respond to foreign and self antigens and in this way promote protection, primarily by production of antibodies. However, recent studies suggest that B cells have diverse functions within the immune system other than antibody production, which could contribute to autoimmunity. This involves organization of lymphoid tissue, regulation of dendritic cells, antigen presentation, activation of T cells and production of cytokines. Both abnormalities in the distribution of B cell subsets, and recent discovery of clinical benefit after B cell depletion highlight the pivotal role of B cells in autoimmunity. This change in view of the role of B cells will be exemplified in one autoimmune disease namely Sjögren's syndrome.

Centola M, Frank MB, Bolstad AI, Alex P, Szanto A, Zeher M, Hjelmervik TO, Jonsson R, Nakken B, Szegedi G, Szodoray P. · Oklahoma Medical Research Foundation, Arthritis and Immunology Program, Oklahoma City, OK, USA. · Scand J Immunol. · Pubmed #16918692 No free full text.

Abstract: Systemic autoimmune rheumatic diseases are of complex aetiology, characterized by an intricate interplay of various factors. A myriad of genes lies behind the heterogeneous manifestations of these diseases, and the overexpression and repression of particular genes form a specific gene-expression profile (genetic fingerprints) that is characteristic to the given disease phenotype. Besides the description of various cell types by using gene-expression profiling, the data should be directly applicable to the design of individual therapeutic protocols for patients suffering from various autoimmune diseases. In this review, we summarize the gene-expression profile, various genetic signatures of different autoimmune diseases and give an overview on the possible interpretations of the data. The application of recent breakthroughs in high-throughput molecular profiling technologies, such as microarray technology has been the basis for a revolution in biomedical research, as well as diagnostics and pharmaceutical development. It is easy to envision a day when personalized medicine, which is the diagnosis and treatment of a given patient with agents and procedures tailored to that patient's genetics, physiology and pathology, will become the standard of care.

Szodoray P, Jonsson R. · Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway. · Scand J Immunol. · Pubmed #16305638 No free full text.

Abstract: Systemic autoimmune diseases, such as Sjögren's syndrome (SS), are characterized by a complex aetiology with multiple pathogenic factors. In SS, disturbed B-cell biology and humoral immunity including B-cell-activating factor (BAFF)-mediated processes have been described. Dysregulated BAFF expression has been described to lead to disease progression and perpetuation of humoral autoimmunity. Moreover, BAFF has been proposed to contribute to the development of B-cell malignancies. In this review, we summarize the current knowledge on BAFF with regard to SS pathology and discuss special features such as germinal centre (GC) formation and lymphomagenesis. Locally, in SS salivary glands, the reduced level of apoptosis among BAFF-expressing cells might lead to longer-existing BAFF expression and thereby maintain signalling for tissue-infiltrating B cells to proliferate and supposedly to become autoantibody-producing plasma cells. We assume that prolonged BAFF signalization may contribute to GC formation and/or lymphoma development in the disease. Finally, we discuss possibilities of novel treatments targeting the BAFF-system in SS.

Bolstad AI, Jonsson R. · Department of Oral Sciences-Periodontics, Faculty of Dentistry, University of Bergen, Aarstadveien 17, N-5009 Bergen, Norway. · Expert Opin Biol Ther. · Pubmed #15952907 No free full text.

Abstract: Sjögren's syndrome (SS) is a complex autoimmune disorder, characterised by mononuclear cell infiltration of exocrine glands, principally the lacrimal and salivary glands. Both cellular, in the form of autoreactive immune cells, and humoral factors, such as autoantibodies, contribute to the expression of the disease. SS can also occur as a systemic disease affecting several organs, and approximately 5% of the patients develop malignant lymphoproliferation. Today SS is considered uncurable. The treatment available is only palliative, and the treatment goals are to manage symptoms and prevent or limit tissue damage. This may involve both local and systemic measures. However, the existing systemic treatment of chronic inflammatory autoimmune diseases has several limitations and unwanted side effects. In recent years the possibility to treat diseases with gene therapy has gained interest and has become a subject of investigation. Given the multitude of factors contributing to the pathogenesis of SS, gene therapy is a major challenge, but may elicit great benefits if successful. Keeping this in mind, the possibility for gene therapeutics in SS in general and potential targets for gene therapy are discussed.

Delaleu N, Jonsson R, Koller MM. · Clinic for Geriatric and Special Care Dentistry, University of Zürich, Zürich, Switzerland. · Eur J Oral Sci. · Pubmed #15819815 No free full text.

Abstract: Sjögren's syndrome (SS) is a chronic autoimmune disease affecting the exocrine glands, primarily the salivary and lacrimal glands. It has been suggested that exogenous agents may trigger SS in genetically predisposed individuals. However, at present, the etiology of SS is far from being understood, and no direct evidence for any of these triggers has been presented. The salivary and lacrimal glands from patients with SS harbor unique and highly selected T- and B-cell populations. Disturbance in glandular cell apoptosis may be one possible explanation for the sicca symptoms in SS. However, discrepancies between glandular destruction and salivary flow give rise to processes causing glandular dysfunction preceding or triggering glandular cell destruction. Recent reports suggested autoantibodies inhibiting neuronal innervation of acinar cells and defective water transport to be implicated in salivary secretion deficiency observed in SS. Several types of autoantibodies have been suggested to contribute to the pathogenesis of SS. However, how the tolerance to these structures is broken down is unknown at present. Studies on B-cell activating factor indicated that diminished apoptosis and disturbed B-cell maturation could be responsible for the occurrence of autoreactive B-cells and B-cell hyperreactivity. B-cell activation may also provide a basis for lymphoma development observed in up to 5% of the patients with SS.

Jonsson R, Gordon TP, Konttinen YT. · Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Armauer Hansen Building, NO-5021 Bergen, Norway. · Curr Rheumatol Rep. · Pubmed #14531959 No free full text.

Abstract: Sjögren's syndrome is a chronic autoimmune and rheumatic disorder of the mucous membranes caused by a lack of proper exocrine secretions, with prominent sicca complaints. The molecular mechanisms of the pathogenesis are virtually unknown, although progress has been made with regard to chemokines, B cell activating factor, and apoptosis. A large number of autoantibodies have been reported in Sjögren's syndrome, some of which relate to impairment of glandular function. Sjögren's syndrome is a female-dominant disease with a late age of onset; most patients contract the disease at the age of 40 to 50 years. Lately, attention has been drawn to the effects of adrenopause in Sjögren's syndrome and on dehydroepiandrosterone and its intracrine metabolism in target tissues. This can influence the maintenance and remodeling of exocrine glands and may explain, in part, another important disease symptom--fatigue.

Bolstad AI, Jonsson R. · Broegelmann Research Laboratory, Department of Microbiology and Immunology, The Gade Institute, University of Bergen, Norway. · Arthritis Res. · Pubmed #12453311 links to  free full text

Abstract: Sjögren's syndrome is a multisystem inflammatory rheumatic disease that is classified into primary and secondary forms, with cardinal features in the eye (keratoconjunctivitis sicca) and mouth (xerostomia). The aetiology behind this autoimmune exocrinopathy is probably multifactorial and influenced by genetic as well as by environmental factors that are as yet unknown. A genetic predisposition to Sjögren's syndrome has been suggested on the basis of familial aggregation, animal models and candidate gene association studies. Recent advances in molecular and genetic methodologies should further our understanding of this complex disease. The present review synthesizes the current state of genetics in Sjögren's syndrome.

Jonsson R, Moen K, Vestrheim D, Szodoray P. · Broegelmann Research Laboratory, University of Bergen, Norway. · Oral Dis. · Pubmed #12108757 No free full text.

Abstract: Sjögren's syndrome is a chronic autoimmune and rheumatic disorder with prominent sicca complaints from the mucous membranes because of lack of proper exocrine secretions. There is no straightforward and simple diagnostic test for Sjögren's syndrome, although several classification criteria have been designed including several oral diagnostic tests. A new set of classification criteria in a joint effort by research groups in Europe and USA has recently been presented. A large number of autoantibodies have been reported in Sjögren's syndrome where, in some cases, the antibodies are correlated with the extent and severity of disease. The finding of serum autoantibodies directed against the muscarinic M3 receptor is an important advance in understanding the pathogenesis of not only the impaired glandular function but also associated features of autonomic dysfunction in some patients. The treatment of primary Sjögren's syndrome is still mainly symptomatic.

Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, Anonymous00126. · Department of Internal Medicine and Rheumatology, Ospedale Villamaria, Piombino, LI, Italy. · Ann Rheum Dis. · Pubmed #12006334 links to  free full text

Abstract: Classification criteria for Sjögren's syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.

Gordon TP, Bolstad AI, Rischmueller M, Jonsson R, Waterman SA. · Department of Immunology, Allergy & Arthritis, Flinders Medical Centre, Bedford Park, South Australia. · Autoimmunity. · Pubmed #11905842 No free full text.

Abstract: Characterisation of autoantibodies and their target autoantigens in primary Sjögren's syndrome (SS) is an important entry point for studying this common systemic autoimmune disease. Diversification of anti-Ro/La responses is believed to occur by a process of determinant spreading following initiation of an autoimmune response to one component, possibly 52-kD Ro (Ro52). Recent evidence supports the ER-resident chaperone Grp78 as a potential candidate in the initiation of an autoimmune response against Ro52, by binding to a Grp78 binding motif in the COOH-terminal region of Ro52. The subsequent diversification of the anti-Ro/La response is influenced by distinct HLA class II alleles. Anti-salivary duct autoantibodies have been revisited and shown to be mimicked by cross-reactive isoantibodies to AB blood group antigens. Identification of autoantibodies that act as antagonists at M3-muscarinic receptors represents an important advance. As well as contributing to the sicca symptoms, the functional effects of these autoantibodies may explain associated features of autonomic dysfunction in patients with SS. Anti-M3 receptor autoantibodies occur in both primary and secondary SS and allow Sjögren's syndrome to be viewed as a disorder of anti-receptor autoimmunity.

Bowman SJ, Pillemer S, Jonsson R, Asmussen K, Vitali C, Manthorpe R, Sutcliffe N, Anonymous00266. · Rheumatology Department, Division of Immunity and Infection, The Medical School, University of Birmingham, UK. · Rheumatology (Oxford). · Pubmed #11600750 links to  free full text

This publication has no abstract.

Jonsson R, Nakken B, Halse AK, Skarstein K, Brokstad K, Haga HJ. · Broegelmanns Forskningslaboratorium Armauer Hansens hus Haukeland Sykehus, Bergen. · Tidsskr Nor Laegeforen. · Pubmed #10806905 No free full text.

Abstract: BACKGROUND: Over the next 3-5 years, the rapid progress in genomic research will enable the discovery of many genes associated with the more common diseases. An example of such a common disease is the rheumatic disorder Sjögren's syndrome, an autoimmune disease. A more precise genetic explanation of the mechanism leading to Sjögren's syndrome remains to be given. MATERIAL AND METHODS: One way of investigating the disease related genes in such complex polygenic diseases is to perform linkage studies in families with two or more affected. Another possibility is to conduct association studies on trios (parents and affected child), case control studies, or other experimental designs. In association studies one is testing if an allele is significantly elevated among patients compared to controls, while in linkage analyses one finds subchromosomal regions that are significantly more often inherited by patients than by healthy family members. RESULTS: The most well defined genetic association in Sjögren's syndrome is currently related to different HLA alleles and their association with anti-Ro/SSA and anti-La/SSB autoantibodies. Additional genetic studies focusing on non-HLA regions are under way. INTERPRETATION: Increased genetic knowledge would allow optimisation of the diagnostic criteria as well as development of new and more effective treatment for Sjögren's syndrome, which causes substantial suffering for a large group of patients.

Humphreys-Beher MG, Brayer J, Yamachika S, Peck AB, Jonsson R. · Department of Oral Biology, The Center for Orphaned Autoimmune Diseases, University of Florida, Gainesville 32610, USA. · Scand J Immunol. · Pubmed #10023850 No free full text.

Abstract: Sjögren's syndrome is characterized by dryness of the eyes and the mouth due to mononuclear cell infiltration of the lacrimal and salivary glands. The aetiology is unknown but autoimmunity is considered to play a significant role in the pathogenesis. Recent studies have focused on the fact that tear and salivary flow involves an entire functional system that includes the mucosal surfaces with adnexes (the site of inflammation), efferent nerve signals sent to the midbrain (lacrimal and salivary response region), and afferent neural signals from the brain to the acinar/ductal epithelial structures in the gland. Mononuclear cell infiltration in exocrine glands can lead to glandular destruction, suggested to be mediated through apoptosis. However, the functional impairment of exocrine glands could be regulated by cytokines and/or antibodies against the muscarinic M3 receptor by inhibiting the neural stimulation of the residual glands. This review discusses the possibility that the pathogenesis of Sjögren's syndrome comprises aberrant immune-mediated neuro-hormonal events.

Iakimtchouk K, Myrmel H, Jonsson R. · No affiliation provided · J Rheumatol. · Pubmed #10493697 No free full text.

This publication has no abstract.

Nordmark G, Kristjansdottir G, Theander E, Eriksson P, Brun JG, Wang C, Padyukov L, Truedsson L, Alm G, Eloranta ML, Jonsson R, Rönnblom L, Syvänen AC. · Section of Rheumatology, Uppsala University, Uppsala, Sweden. · Genes Immun. · Pubmed #19092842 No free full text.

Abstract: Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P=2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.

Delaleu N, Madureira AC, Immervoll H, Jonsson R. · The Gade Institute, University of Bergen, Bergen, Norway. · Arthritis Rheum. · Pubmed #18668586 links to  free full text

Abstract: OBJECTIVE: To investigate a potential immunomodulatory effect of the 60-kd heat-shock protein (Hsp60) on experimental spontaneous Sjögren's syndrome (SS). METHODS: Seven-week-old nonobese diabetic (NOD) mice were immunized with eukaryotic Hsp60 or an Hsp60-derived peptide (amino acid residue [aa] 437-460). At 21 weeks of age, nondiabetic mice were investigated for salivary gland inflammation, exocrine function, and extraglandular disease manifestations. In addition, biomarker profiles comprising 87 analytes in serum and 75 in saliva were analyzed. RESULTS: In mice immunized with Hsp60 and aa 437-460, SS-related histopathologic features were significantly reduced compared with NOD controls. In addition, 50% of Hsp60-injected mice and 33% of aa 437-460-injected mice retained normal exocrine function. Both treatments induced similar changes in biomarker profiles. Notably, levels of circulating interferon-gamma-inducible 10-kd protein (IP-10) and eotaxin were decreased significantly after treatment. Anti-type 3 muscarinic acetylcholine receptor (anti-M3R) IgG1, interleukin-10, and leptin discriminated best between the different treatment groups. Successful prevention of hyposalivation was accompanied by quantitative alterations in 36 biomarkers, of which 19 mediators of inflammation declined to levels comparable with those found in BALB/c mice. Low secreted vascular endothelial growth factor A was the most accurate predictor of successful prevention of hyposalivation. Low salivary granulocyte chemotactic protein 2 was identified as the best predictor of normal secretory function across the strains. CONCLUSION: Immunization with Hsp60 and its peptide aa 437-460 led to inhibition of SS in NOD mice. Comprehensive analyses revealed specific biomarker signatures capable of predicting treatment group and treatment outcome. Molecules involved in inflammatory chemotaxis, neovascularization, and regulatory pathways caused the differences displayed by the biomarker profiles.