- •Preface
- •Contents
- •Contributors
- •1 Introduction
- •1.1 Historical Background
- •1.2 Pitfalls in Diagnosis and Methodology
- •1.3 Methods to Assess Disease Activity
- •1.4 Summary
- •References
- •2.1 Introduction
- •2.4 Pearls of Wisdom
- •References
- •3.1 Background: Overall Approach to Patient Care
- •3.1.1 Pearl
- •3.1.2 Pearl
- •3.2 Diagnosis Criteria and Laboratory Tests
- •3.2.1 Myth
- •3.2.2 Pearl
- •3.2.3 Myth
- •3.2.4 Myth
- •3.2.5 Pearl
- •3.2.6 Pearl
- •3.2.7 Pearl
- •3.3 Myths and Pearls About Clinical Presentations
- •3.3.1 Pearl
- •3.3.2 Myth
- •3.3.3 Pearl
- •3.3.4 Pearl
- •3.3.5 Pearl
- •3.3.6 Pearl
- •3.3.7 Pearl
- •3.3.8 Pearl
- •3.3.9 Pearl
- •3.3.10 Pearl
- •3.3.11 Pearl
- •3.3.12 Pearl
- •3.3.13 Myth
- •3.3.14 Pearl
- •3.3.15 Pearl
- •3.3.16 Myth
- •3.4 Myths and Pearls About Pathogenesis
- •3.4.1 Myth
- •3.4.2 Pearl
- •3.4.3 Pearl
- •3.4.4 Myth
- •3.4.5 Pearl
- •3.5 Myths and Pearls About Treatment
- •3.5.1 Myth
- •3.5.2 Pearl
- •3.5.3 Pearl
- •3.5.4 Pearl
- •3.5.5 Pearl
- •3.5.6 Pearl
- •3.5.7 Pearl
- •References
- •4.1 Background and Overview
- •4.1.1 Need for Written Information
- •4.1.2 Use of Internet as a Method to Provide Information
- •4.1.3 Patient Access to Computers
- •4.1.4 Types of Information Supplied to Patients and Referring Physicians
- •4.2.1 Background: The Confusion Surrounding Criteria for Autoimmune Disorders
- •4.2.5 Criteria for Fibromyalgia
- •4.3 Laboratory Results for ANA Often Drive Clinical Diagnosis
- •4.5 Status of Biologic Drugs in SS Patients
- •4.6 Ocular Treatment
- •4.6.2 Blepharitis
- •4.7 Therapy of Oral Manifestations
- •4.7.1 Prevention of Dental Caries
- •4.7.2 Oral Candida Prevention and Treatment
- •4.8 Summary
- •References
- •5.1 Introduction
- •5.4 Outcome Measures in SS
- •5.4.1 Outcome Measures in SS: A Brief History
- •5.6 Outcome Measures in SS: The Italian Study
- •References
- •6.1 Introduction
- •6.2 Benign Lymphoepithelial Lesion in Salivary Glands
- •6.3.1.2 Ectopic Germinal Center Formation
- •6.3.1.3 Clinical Implications of Ectopic Germinal Center Formation
- •6.4 Late Breaking Update
- •References
- •7.1 Conventional Radiographs
- •7.1.1 Sialography
- •7.2 Computer Tomography
- •7.3 Ultrasound
- •7.4 Magnetic Resonance Imaging
- •7.5 Nuclear Medicine
- •7.5.1 Scintigraphy
- •7.6 Comparison of Nuclear Medicine, Ultrasound, and MRI
- •References
- •8.1 Introduction
- •8.2 Evidence Supporting a Genetic Component in SS
- •8.4 Lessons from SLE and Other Autoimmune Diseases
- •8.5 Genes Implicated in SS
- •8.7 Insights from Genomic and Proteomic Studies
- •8.8 Conclusion
- •References
- •9.1 Introduction
- •9.2.4 Antibodies to Nuclear Protein NA14
- •9.3.1 Initiation Phase
- •9.3.2 Recognition Phase
- •9.3.3 Establishment Phase: Autoreactive T and B Lymphocytes Dysregulation and Aberrant Cytokines Production
- •9.3.5 Effector Phase
- •References
- •10.1 Introduction
- •10.2.1 Ro/La RNP Particles
- •10.2.3 The Ro60 Autoantigen
- •10.2.4 The Ro52 Autoantigen
- •10.2.5 The Multifunctional Chaperone Calreticulin
- •10.4.2 Early Epitope Recognition in Autoimmune Diseases and Epitope Spreading
- •References
- •11.2 Acinar Cell
- •11.3 Neuropeptides
- •11.3.1 Acinotrophic Neurogenic Stimuli
- •11.4 Sex Steroids
- •11.4.1 Steroidogenesis in Adrenal Glands
- •11.4.2 Regulation of the Adrenal Steroidogenesis
- •11.4.4 Peripheral Intracrine Synthesis of Sex Steroids
- •11.4.5 Intracrine Sex Steroids Production in pSS and sSS
- •11.4.7 Putative Mechanism of Action of the Intracrine Processing Defect
- •11.5.1 General Histopathology
- •11.5.2 T Lymphocytes
- •11.5.3 B Lymphocytes
- •11.5.4 Chemokines
- •11.5.5 Adhesion Molecules
- •11.5.6 Cytokines
- •References
- •12.1 Background
- •12.2 Incidence, Symptomatic Presentation, and Impact on Quality of Life
- •12.3 Diagnostic Screening Examination
- •12.4 Overview of Dry Eye Management
- •12.4.1 Dry Eyes Deserve Respect and Careful Monitoring
- •12.4.2 Four Levels of Severity Differentiation
- •12.4.2.1 Level 1
- •12.4.2.2 Level 2
- •12.4.2.3 Level 3
- •12.4.2.4 Level 4
- •12.5.2 General Guidelines for the Dry Eye Patient
- •12.6 Additional Types of Therapy
- •12.7 Moisture Preservation and Oral Medications
- •12.7.2 Punctal Plugs
- •12.8 Oral Medications and Supplements
- •12.8.1 Dietary Fatty acids (Flaxseed Oil) and Dry Eyes
- •12.8.2 Oral Medications
- •12.9 Complications Associated with Ophthalmologic Cosmetic Procedures
- •12.10 Summary
- •References
- •13.1 Introduction
- •13.2 The Lacrimal Functional Unit (LFU)
- •13.3 The General Role of the LFU in Normal and Pathological Situation
- •13.4 Innervation of the Lacrimal Functional Unit
- •13.5 Efferent Structures
- •13.5.1 Lacrimal Glands
- •13.5.2 Goblet Cells
- •13.5.3 Meibomian Glands
- •13.6 Maintenance of the Lacrimal Functional Unit
- •13.6.1 Hormonal
- •13.6.2 Immunological
- •13.8 The Normal Ocular Surface Environment
- •13.9 The Makeup of the Tear Film
- •13.9.1 Hydrated Mucin Gel
- •13.9.3 Aqueous Components
- •13.10 The Pathophysiology of Dry Eye
- •13.10.1 Loss of Hormonal Support
- •13.10.2.1 Afferent Arm
- •13.10.2.2 Efferent Arm
- •13.11 Loss of Ocular Surface Homeostasis
- •13.11.1 Alterations of the Mucin, Lipid, and Aqueous Composition
- •13.11.2 Mucins
- •13.11.3 Lipids
- •13.12 The Ocular Surface Immunosuppressive Environment
- •13.14 Late-Breaking Additions
- •References
- •14.1 Saliva in Oral Health and Disease
- •14.1.1 Saliva in Dental and Mucosal Defense
- •14.1.2 Assessment of Oral Dryness
- •14.1.2.2 Objective Measurements of Hyposalivation
- •14.2 Saliva as a Diagnostic Fluid
- •14.2.1 Biomarker Analyses in Saliva
- •14.3 Complications of Oral Dryness
- •14.3.1 Management of Xerostomia
- •14.3.2 Caries Preventive Measures
- •14.3.2.3 Dietary Advice
- •14.3.2.4 The Time Factor
- •References
- •15.1.1 Endothelial Cells
- •15.1.2 Epithelial Cells
- •15.1.3 T cells
- •15.1.4 B cells
- •15.2 Mechanisms Mediating Salivary Gland Dysfunction
- •15.2.1 Acinar Cell Innervation and Humoral Immunity
- •15.2.3 Fluid Movement in the Salivary Glands and Aquaporins
- •15.3.1 Environmental Factors
- •15.3.2 Secondary Signals
- •15.3.3 Apoptosis, Autoantigens, and Potential Danger Signals in the Salivary Glands
- •15.3.4 Immunoregulation
- •15.3.5 B-cell-Activating Factor
- •15.3.6 Hormones
- •15.3.7 Microchimerism
- •References
- •16.1 Introduction
- •16.2 Diagnosis
- •16.3 Head and Neck Manifestations
- •16.3.1 Ophthalmic
- •16.3.2 Oral
- •16.3.3 Otologic
- •16.3.4 Rhinologic
- •16.3.5 Laryngeal
- •16.3.6 Esophageal
- •16.3.7 Thyroid
- •16.3.8 Neurological
- •16.4 Treatment
- •16.5 Conclusion
- •16.6 Patient Handout
- •References
- •17.1 Introduction
- •17.2 Cutaneous/Dermatologic Manifestations
- •17.4 Endocrinopathic/Pancreatic Manifestations
- •17.4.1 Hypothyroidism
- •17.4.2 Adrenal
- •17.4.3 Pancreas
- •17.5 Pulmonary Manifestations
- •17.5.1 Interstitial Pneumonitis
- •17.6.1 Pericarditis
- •17.6.2 Autonomic Manifestations
- •17.6.3 Congenital Heart Block
- •17.6.4 Accelerated Atherosclerosis
- •17.7 Gastrointestinal Manifestations
- •17.8 Hepatic and Pancreatic Manifestations
- •17.9 Renal/Urological Manifestations
- •17.10 Hematologic Manifestations
- •17.11 Obstetrical/Gynecological Manifestations
- •17.12 Vasculitis
- •17.12.1 CNS Arteritis in the SS Patient
- •17.13 Differential Diagnosis of Extraglandular Manifestations of SS
- •17.13.1 Medications and Other Metabolic Disorders
- •17.14 Manifestations and Differential Diagnosis in the Pediatric Population
- •17.15 Summary
- •17.16 Late-Breaking Updates
- •References
- •18.1 Introduction
- •18.2 Treatment and Management of Cutaneous Manifestations
- •18.2.1 Treatment of Dry Skin
- •18.3 Arthralgia/Arthritis
- •18.4.1 Chronic Cough
- •18.5 Renal Manifestations
- •18.5.1 Interstitial Nephritis
- •18.5.1.1 Glomerular Disease
- •18.6 Gastrointestinal Manifestations
- •18.6.1 Mesenteric Vasculitis
- •18.6.2 Primary Biliary Cirrhosis
- •18.7 Urologic
- •18.8 Therapeutic Management of Obstetrical/Gynecological Manifestations
- •18.9 Special Precautions at the Time of Surgery
- •18.10 Vaccinations in the SS Patient
- •18.11 Summary
- •18.12 Late-Breaking Updates
- •References
- •19.1 Introduction
- •19.3.1 Fatigue
- •19.3.2 Musculoskeletal
- •19.3.4 Gastrointestinal Manifestations
- •19.3.5 Liver Involvement
- •19.3.6 Lung Involvement
- •19.3.7 Kidney Involvement
- •19.3.8 Neurologic Involvement
- •19.3.9 Hematologic Involvement
- •19.4 Conclusions
- •References
- •20.1 Introduction
- •20.2 Diagnosis
- •20.3 Staging and Evaluation of Treatment Response
- •20.4 Treatment
- •20.5 Summary/Pearls
- •References
- •21.1 Introduction
- •21.2 What Is Fatigue?
- •21.3 Potential Causes of Fatigue in pSS
- •21.3.1 Biological
- •21.3.1.1 Cytokines
- •21.3.1.2 Neuroendocrine
- •21.3.1.3 Sleep
- •21.3.2 Psychosocial
- •21.3.2.1 Depression
- •21.3.2.2 Fibromyalgia
- •21.4 Measurement of Fatigue and Other Extraglandular Symptoms
- •21.6 Potential Approaches to Treatment of Fatigue and Other Extraglandular Symptoms
- •21.7 Measurement of Dryness (Sicca) Symptoms
- •21.8 Data from Existing Clinical Studies Addressing Dryness in pSS
- •21.9 Conclusion: Clinical Trial Outcomes
- •References
- •22.1 Introduction
- •22.2 Clinical Evaluation of Neurological Findings in SS
- •22.3.1 Role of Cell-Mediated Immunity
- •22.3.2 The Role of Antibodies Associated with Neurological Manifestations of SS
- •22.4 Investigations
- •22.4.1 Neurophysiology
- •22.4.2 Autonomic Studies
- •22.4.3 MR Imaging of the Spinal Cord
- •22.5 Peripheral Clinical Manifestations
- •22.6 Painful Sensory Neuropathies
- •22.6.1 Differential Diagnosis
- •22.7 Sensory Ataxic Neuropathy
- •22.7.1 Differential Diagnosis
- •22.8 Neuromuscular Weakness
- •22.8.1 Differential Diagnosis
- •22.9 Neuromuscular Pain
- •22.9.1 Differential Diagnosis
- •22.10 Autonomic Neuropathy
- •22.10.1 Differential Diagnosis
- •22.11 Trigeminal Neuropathy and Other Cranial Neuropathies
- •22.12 Central Nervous System Manifestations
- •22.12.2 Cognitive Impairment
- •22.12.3 Movement Disorders
- •22.12.4 Aseptic meningitis and Meningoencephalitis
- •22.12.5 Other Neurological Disorders
- •22.13 Investigations of Central Nervous System Manifestations
- •22.13.1 Serology
- •22.13.2 Spinal Fluid
- •22.13.4 Nuclear Brain Imaging Studies
- •22.13.5 Cerebral Angiography
- •22.14 The Puzzling Neurological Manifestations of Fibromyalgia
- •22.15 Interpretation of ANA in the Patient with Neurological Symptoms
- •22.16 Treatment
- •22.16.1 Peripheral Nervous System Treatment: Overview
- •22.16.2 Painful Sensory Neuropathies
- •22.16.3 Ataxic Neuropathy
- •22.16.4 Motor and Sensory Neuropathies
- •22.16.5 Central Nervous System Treatment
- •22.16.6 Side Effects of Immunosuppressive Therapy
- •22.17 Summary of Special Points to Neurologists
- •22.17.3 Relationship of Neurological Symptoms to Sicca Manifestations
- •22.18 Summary for Rheumatologists
- •References
- •23.1 Introduction
- •23.3.1 Labial Minor Salivary Gland Biopsy
- •23.3.2 Sialography
- •23.4 The Application of a Bite Guard
- •References
- •24.1 Introduction
- •24.2 How to Provide the Essential Tear Components to the Ocular Surface
- •24.3 Use of Autologous Serum Eye Drops for the Treatment of Dry Eye
- •24.4 Ongoing Research with Autologous Serum Eye Drops
- •24.5 Preparation of Autologous Serum Eye Drops
- •24.8 Conclusion
- •References
- •References
- •27.1 A Disease of Antiquity in Ancient China
- •References
- •References
- •References
- •30.1 Introduction
- •30.2 Evaluation of Systemic Features of Primary SS
- •30.2.4 Comparisons of Systemic Disease Activity Scores
- •30.3.1 The SSI: Sicca Symptoms Inventory
- •30.4 Conclusion
- •References
- •31.1 Clinical Practice Guidelines
- •31.2 Clinical Trials Consortium
- •31.3 Professional Education and Awareness
- •31.4.1 Rheumatology Working Group
- •31.4.2 Ocular Working Group
- •31.4.3 Oral Working Group
- •31.4.5 Facilitator for Both Initiatives
- •32.1 Introduction
- •32.2 For Which Patients Should Biological Therapy Be Considered?
- •32.7 BAFF Inhibition
- •32.8 Interferon Inhibition
- •32.9 Gene Therapy
- •32.10 Other Targets for Biologic Therapy
- •32.11 Conclusions and Future Directions
- •References
- •33.1 Overview of the Pathogenesis of pSS
- •33.1.1 Initial Steps
- •33.1.1.1 Breach of Self-tolerance
- •33.1.1.2 Activation of Innate Immunity and Interferon Pathways
- •33.1.1.4 Regulation of BAFF Secretion
- •33.1.1.6 Other Cytokines, Chemokines, and Adhesion Molecules Are Involved in the Pathogenesis of the Disease
- •33.1.3 Glandular Hypofunction Rather Than Glandular Destruction
- •33.2 Emerging Therapies
- •33.2.1 Prerequisite for the Development of New Drugs in pSS
- •33.2.1.1 Disease Activity Score
- •33.2.1.2 Selection of Patients
- •33.2.3.1 Inhibition of the Triggering Factors of IFN Activation
- •33.2.3.2 IFN Blockade
- •33.2.3.3 Antagonists of BAFF and APRIL
- •33.2.3.4 B-cell Depletion
- •33.2.3.5 Other B-cell-Targeted Therapy: Other Anti-CD20 and Anti-CD22
- •33.3 Other Therapeutic Perspectives
- •33.3.1 Inhibition of Other Cytokines and Chemokines
- •33.3.3 Gene Therapy
- •33.4 Conclusion
- •References
- •34.1 Introduction
- •34.5 Conclusion
- •References
- •Index
33 Looking into the Future—Emerging Therapies Based on Pathogenesis |
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Of note, approximately 10% of treated patients of the different studies (case reports, open, and controlled studies) presented serum sickness-like disease 3Ð7 days after rituximab infusion (fever, arthralgia, and purpura). This complication, usually benign, must be differentiated from immediate infusion reactions which are probably due to cytokines release and which will not recur after the next infusions. Serum sickness disease may occur after treatment with chimeric antibodies. Curiously, it is exceptional after treatment of lymphoma with rituximab and has not been described in the randomized control trials of rituximab in RA. Cases of serum sickness diseases have also been described in open studies of rituximab in lupus. The higher frequency of serum sickness disease in SS may be due to hypergammaglobulinemia, which is much more common in SS and SLE than in RA.
33.2.3.5 Other B-cell-Targeted Therapy: Other Anti-CD20 and Anti-CD22
With the development of humanized or human anti-CD20 monoclonal antibodies or small oral molecules against CD20, the interest of B-cell inhibition using other agents might be further evaluated in pSS.
An open study including 15 patients has been performed with epratuzumab, an anti-CD22 monoclonal antibody [58]. This anti-B-cell antibody leads to only partial B-cell depletion (50% in blood). The results of this open study are interesting with improvement of dryness, fatigue, and pain VAS. Moreover, salivary ßow seems to be improved in patients with early disease. A controlled trial is now necessary to conÞrm these data.
with BAFF, the formation of germinal center-like structures in salivary glands, also deserves to be evaluated. Indeed, baminercept, a lymphotoxin- β receptor immunoglobulin fusion protein, has a dramatic effect in reducing salivary B-cell inÞltrates of NOD mice. Moreover, salivary ßow was partially restored in the treated mice [59].
33.3.2Inhibition of T-cell Co-stimulation
Abatacept (CTLA-Ig), which has demonstrated its efÞcacy in RA, could be of therapeutic interest in pSS. Abatacept could also interact with the antigen-presenting cell properties of epithelial cells, which express CD80 and CD86.
33.3.3 Gene Therapy
For patients with glandular symptoms only, it could be speculated that progress in designing harmless vectors might make gene therapy become a true possibility in pSS [60, 61]. The good candidate genes for gene therapy remain to be determined. Of interest is the ongoing evaluation of the possibility of aquaporin 1 gene local livery in the salivary glands, currently evaluated in the NIH for radiotherapy-related dryness (phase I).
33.4Conclusion
Looking into the future for therapies of pSS, we can feel rather optimistic. pSS is a wonderful model of autoimmunity for translational research, with an easy access to target organs of autoimmu-
33.3Other Therapeutic Perspectives nity. Interestingly, recent genetic and pathogenic
33.3.1Inhibition of Other Cytokines and Chemokines
Inhibition of IL-6, which has a demonstrated efÞcacy in RA, or IL-21, other pivotal cytokines for B-cell activation, might be of interest in pSS. Inhibition of lymphotoxin-β, which allows, along
studies evidenced number of similarities between pSS and lupus, and pSS could be considered as a sort of lupus of mucosa. In pSS like in lupus, new pathogenic pathways have been and will be unraveled, resulting in the deÞnition of new targets. To convert our optimism into the improvement of patients in daily care, a consensual disease activity score must be validated and
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clinicians and pharmaceutical companies have to design new trials with adequate inclusion criteria. Indeed, pSS is not a lost battle for the development of efÞcient biotherapies!
References
1.Christodoulou MI, Kapsogeorgou EK, Moutsopoulos NM, Moutsopoulos HM. Foxp3+ T-regulatory cells in SjogrenÕs syndrome: correlation with the grade of the autoimmune lesion and certain adverse prognostic factors. Am J Pathol. 2008;173:1389Ð96.
2.Gottenberg JE, Lavie F, Abbed K, Gasnault J, Le Nevot E, Delfraissy JF, TaouÞk Y, Mariette X. CD4 CD25high regulatory T cells are not impaired in patients with primary SjogrenÕs syndrome. J Autoimmun. 2005;24:235Ð42.
3.Hjelmervik TO, Petersen K, Jonassen I, Jonsson R, Bolstad AI. Gene expression proÞling of minor salivary glands clearly distinguishes primary SjšgrenÕs syndrome patients from healthy controls. Arthritis Rheum. 2005;52:1534Ð44.
4.Gottenberg JE, Cagnard N, Lucchesi C, Letourneur F, Mistou S, Lazure T, Jacques S, Ba N, Ittah M, Lepajolec C, Labetoulle M, Ardizzone M, Sibilia J, Fournier C, Chiocchia G, Mariette X. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary SjogrenÕs syn-
drome. Proc Natl Acad Sci USA. 2006;103:2770Ð5. 5. Emamian ES, Leon JM, Lessard CJ, Grandits M, Baechler EC, Gaffney PM, Segal B, Rhodus NL, Moser KL. Peripheral blood gene expression proÞling in SjšgrenÕs syndrome. Genes Immun.
2009;10:285Ð96. Epub 2009 Apr 30.
6.Miceli-Richard C, Comets E, Loiseau P, Puechal X, Hachulla E, Mariette X. Association of an IRF5 gene functional polymorphism with SjogrenÕs syndrome. Arthritis Rheum. 2007;56:3989Ð94.
7.Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 2000;404:995Ð9.
8.Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T, Kimberly R. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human SjogrenÕs syndrome. Ann Rheum Dis. 2003;62: 168Ð71.
9.Sellam J, Miceli-Richard C, Gottenberg JE, Ittah M, Lavie F, Lacabaratz C, Gestermann N, Proust A, Lambotte O, Mariette X. Decreased BAFF-R on peripheral lymphocytes associated with increased disease activity in primary SjogrenÕs syndrome and systemic lupus erythematosus. Ann Rheum Dis. 2007 Jun;66:790Ð7.
10.Stein JV, L—pez-Fraga M, Elustondo FA, CarvalhoPinto CE, Rodr’guez D, G—mez-Caro R, De Jong J, Mart’nez-A C, Medema JP, Hahne M. APRIL modulates B and T cell immunity. J Clin Invest. 2002;109:1587Ð98.
11.Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. TACI is mutant in common variable immunodeÞciency and IgA deÞciency. Nat Genet. 2005;37:829Ð34.
12.Yan M, Wang H, Chan B, Roose-Girma M, Erickson S, Baker T, Tumas D, Grewal IS, Dixit
VM. Activation and accumulation of |
B cells |
in TACI-deÞcient mice. Nat Immunol. |
2001;2: |
638Ð43. |
|
13.Ittah M, Miceli-Richard C, Eric Gottenberg J, Lavie F, Lazure T, Ba N, Sellam J, Lepajolec C, Mariette X. B-cell activating factor of the TNF family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary SjšgrenÕs syndrome. Arthritis Res Ther. 2006 8;R51
14.Kapsogeorgou E, Manoussakis MN, The central role of epithelial cells in SjogrenÕs syndrome or autoimmune epithelitis. Autoimmun Rev. 2004;3(Suppl 1): S61Ð3.
15.Lavie F, Miceli-Richard C, Quillard J, Roux S, Leclerc P, Mariette X. Overexpression of BAFF in T cells inÞltrating labial salivary glands from patients with SjšgrenÕs syndrome. J Pathol. 2004;202: 496Ð502.
16.Morimoto S, Nakano S, Watanabe T, Tamayama Y, Mitsuo A, Nakiri Y, Suzuki J, Nozawa K, Amano H, Tokano Y, Kobata T, Takasaki Y. Expression of B-cell activating factor of the tumour necrosis factor family (BAFF) in T cells in active systemic lupus erythematosus: the role of BAFF in T cell-dependent B cell pathogenic autoantibody production. Rheumatology (Oxford) 2007;46:1083Ð6.
17.Lavie F, Miceli-Richard C, Ittah M, Sellam J, Gottenberg JE, Mariette X. B-cell activating factor of the tumour necrosis factor family expression in blood monocytes and T cells from patients with primary SjšgrenÕs syndrome. Scand J Immunol. 2008;67:185Ð92.
18.Daridon C, Devauchelle V, Hutin P, Le Berre R, Martins-Carvalho C, Bendaoud B, Dueymes M, Saraux A, Youinou P, Pers JO. Aberrant expression of BAFF by B lymphocytes inÞltrating the salivary glands of patients with primary SjšgrenÕs syndrome. Arthritis Rheum. 2007 ;56:1134Ð44.
19.Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002;3:822Ð829.
20.Ittah M, Miceli-Richard C, Gottenberg JE, Sellam J, Eid P, Lebon P, Pallier C, Lepajolec C, Mariette X. Viruses induce high expression of B cell-activating factor by salivary gland epithelial cells through Toll-like receptorand type-I interferon-dependent
33 Looking into the Future—Emerging Therapies Based on Pathogenesis |
479 |
|
|
and -independent pathways. Eur J Immunol. 2008 Apr;38:1058Ð64.
21.Ittah M, Miceli-Richard C, Gottenberg JE, Sellam J, Lepajolec C, Mariette X. B-cell-activating factor expressions in salivary epithelial cells after dsRNA virus infection depends on RNA-activated protein kinase activation. Eur J Immunol. 2009;39:1271Ð9.
22.Gottenberg JE, Sellam J, Ittah M, Lavie F, Proust A, Zouali H, Sordet C, Sibilia J, Kimberly RP, Mariette
X, Miceli-Richard C. No evidence for an association between the −871 T/C promoter polymorphism in the B-cell-activating factor gene and primary SjšgrenÕs syndrome. Arthritis Res Ther. 2006;8:R30. Epub 2006 Jan 9. PubMed PMID: 16507129.
23.Salomonsson S, Jonsson MV, Skarstein K, Brokstad KA, Hjelmstršm P, Wahren-Herlenius M, Jonsson R. Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with SjšgrenÕs syndrome. Arthritis Rheum. 2003;48:3187Ð3201.
24.Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. Lymphoma and other malignancies in primary SjogrenÕs syndrome. A cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006;65:796Ð803.
25.Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165:2337Ð2344.
26.Novak AJ, Grote DM, Stenson M, Ziesmer SC, Witzig TE, Habermann TM, Harder B, Ristow KM, Bram RJ, Jelinek DF, Gross JA, Ansell SM. Expression of BLyS and its receptors in B-cell nonHodgkin lymphoma: correlation with disease activity and patient outcome. Blood 2004;104: 2247Ð53.
27.Ogawa N, Ping L, Zhenjun L, Takada Y, Sugai S. Involvement of the interferon-gamma-induced T cellattracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with SjogrenÕs syndrome. Arthritis Rheum. 2002;46:2730Ð41.
28.Barone F, Bombardieri M, Manzo A, Blades MC, Morgan PR, Challacombe SJ, Valesini G, Pitzalis C. Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in SjogrenÕs syndrome. Arthritis Rheum. 2005;52:1773Ð84.
29.Nguyen CQ, Hu MH, Li Y, Stewart C, Peck AB. Salivary gland tissue expression of interleukin-23 and interleukin-17 in SjšgrenÕs syndrome: Þndings in humans and mice. Arthritis Rheum. 2008;58: 734Ð43.
30.Gottenberg JE, Busson M, Loiseau P, Cohen-Solal J, Lepage V, Charron D, Sibilia J, Mariette X. In primary SjogrenÕs syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response. Arthritis Rheum. 2003;48:2240Ð5.
31.Kariuki SN, Kirou KA, MacDermott EJ, BarillasArias L, Crow MK, Niewold TB. Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo. J Immunol. 2009 Jan 1;182:34Ð8.
32.Dawson LJ, Fox PC, Smith PM. Sjogrens
syndromeÑthe non-apoptotic model |
of glan- |
dular hypofunction. Rheumatology |
(Oxford) |
2006;45:792Ð8. |
|
33.Ohlsson M, Skarstein K, Bolstad AI, Johannessen AC, Jonsson R. Fas-induced apoptosis is a rare event in SjogrenÕs syndrome. Lab Invest. 2001;81:95Ð105.
34.Zoukhri D, Kublin CL. Impaired neurotransmitter
release from lacrimal and salivary gland nerves of a murine model of SjogrenÕs syndrome. Invest Ophthalmol Vis Sci. 2001;42:925Ð32.
35.Dawson LJ, CaulÞeld VL, Stanbury JB, Field AE, Christmas SE, Smith PM. Hydroxychloroquine therapy in patients with primary SjogrenÕs syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase. Rheumatology (Oxford) 2005;44:449Ð55.
36.Waterman SA, Gordon TP, Rischmueller M. Inhibitory effects of muscarinic receptor autoan-
tibodies on |
parasympathetic |
neurotransmission |
||
in |
SjogrenÕs |
syndrome. |
Arthritis |
Rheum. |
2000;43:1647Ð54. |
|
|
||
37.Beroukas D, Hiscock J, Jonsson R, Waterman SA, Gordon TP. Subcellular distribution of aquaporin 5 in salivary glands in primary SjšgrenÕs syndrome. Lancet 2001;358:1875Ð76.
38.Vitali C, Palombi G, Baldini C, Benucci M, Bombardieri S, Covelli M, Del Papa N, De Vita S, Epis O, Franceschini F, Gerli R, Govoni M, Bongi SM, Maglione W, Migliaresi S, Montecucco C, OreÞce M, Priori R, Tavoni A, Valesini G. SjšgrenÕs syndrome disease damage index and disease activity index: scoring systems for the assessment of disease damage and disease activity in SjšgrenÕs syndrome, derived from an analysis of a cohort of Italian patients. Arthritis Rheum. 2007;56:2223Ð31.
39.Bowman SJ, Sutcliffe N, Isenberg DA, Goldblatt F, Adler M, Price E, Canavan A, Hamburger J, Richards A, Rauz S, Regan M, Gadsby K, Rigby S, Jones A, Mathew R, Mulherin D, Stevenson A, Nightingale P. SjšgrenÕs systemic clinical activity index (SCAI)Ña systemic disease activity measure for use in clinical trials in primary SjšgrenÕs syndrome. Rheumatology (Oxford) 2007;46:1845Ð51.
40.Seror R, Ravaud P, Bowman S, Baron G, Tzioufas A, Theander E, Gottenberg JE, Bootsma H, Mariette X, Vitali C. EULAR SjogrenÕs syndrome disease activity index (ESSDAI): development of a consensus systemic disease activity index in primary SjogrenÕs syndrome. Ann Rheum Dis. 2009 Jun 28; Epub ahead of print.
41.Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, Combe B, PuŽchal X, Pennec Y, Sauvezie B, Perdriger A, Hayem G, Janin A, Sibilia
480 |
J.-E. Gottenberg and X. Mariette |
|
|
J. InefÞcacy of inßiximab in primary SjšgrenÕs syndrome. Results of the randomized controlled Trial of Remicade In Primary SjšgrenÕs Syndrome (TRIPSS). Arthritis Rheum. 2004;50:1270Ð6.
42.Sankar V, Brennan MT, Kok MR, Leakan RA, Smith JA, Manny J, Baum BJ, Pillemer SR. Etanercept in SjogrenÕs syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum. 2004;50:2240Ð5.
43.Mavragani CP, Niewold TB, Moutsopoulos NM, Pillemer SR, Wahl SM, Crow MK. Augmented interferon-alpha pathway activation in patients with SjšgrenÕs syndrome treated with etanercept. Arthritis Rheum. 2007;56:3995Ð4004.
44.Wallace DJ, Petri M, Olsen N, et al. MEDI-545, an anti-interferon alpha monoclonal antibody, shows evidence of clinical activity in systemic lupus erythematosus. Arthritis Rheum. 2007;56:S526.
45.Stohl W, Chatham W, Weisman M, et al. Belimumab (BmAb), a novel fully human monoclonal antibody to B-lymphocyte stimulator (BLyS), selectively modulates B-cell sub-populations and immunoglobulins in a heterogeneous rheumatoid arthritis subject population. Arthritis Rheum. 2005;52:S444
46.Petri M, Furie R, Ginzler E, et al. Novel combined response endpoint and systemic lupus erythematosus (SLE) ßare index (SFI) demonstrate belimumab (fully human monoclonal antibody to BLyS) improves or stabilizes SLE disease activity and reduces ßare rate over 2.5 years of therapy. Arthritis Rheum. 2007;56:S527 (abstract 316).
47.Toubi E, Kessel A, Slobodin G, Boulman N, Pavlotzky E, Zisman D, Rozenbaum M, Rosner I. Changes in macrophage function after rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66:818Ð20. Epub 2006 Dec 5.
48.Cambridge G, Stohl W, Leandro MJ, Migone TS,
Hilbert DM, Edwards JC. Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum. 2006;54: 723Ð32.
49.Pers JO, Devauchelle V, Daridon C, Bendaoud B, Le Berre R, Bordron A, Hutin P, Renaudineau Y, Dueymes M, Loisel S, Berthou C, Saraux A, Youinou P. BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with SjšgrenÕs syndrome. Arthritis Rheum. 2007;56:1464Ð77.
50.Lavie F, Miceli-Richard C, Ittah M, Sellam J, Gottenberg JE, Mariette X. Increase of B-cell activating factor of the TNF family (BAFF) after rituximab: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007;66:700Ð3.
51.Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary SjogrenÕs syndrome: an open-label phase II study. Arthritis Rheum. 2005;52:2740Ð50.
52.Devauchelle-Pensec V, Pennec Y, Morvan J, et al. Improvement of SjšgrenÕs syndrome after two infusions of rituximab (anti-CD20). Arthritis Rheum. 2007;57:310Ð7.
53.Somer BG, Tsai DE, Downs L, et al. Improvement in SjogrenÕs syndrome following therapy with rituximab for marginal zone lymphoma. Arthritis Rheum. 2003;49:394Ð8.
54.Voulgarelis M, Giannouli S, Tzioufas AG, et al. Long term remission of SjogrenÕs syndrome associated aggressive B cell non-HodgkinÕs lymphomas following combined B cell depletion therapy and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Ann Rheum Dis. 2006;65: 1033Ð7.
55.Seror R, Sordet C, Guillevin L, Hachulla E, Masson C, Ittah M, Candon S, Le Guern V, Aouba A, Sibilia J, Gottenberg JE, Mariette X. Tolerance and efÞcacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary SjogrenÕs syndrome. Ann Rheum Dis. 2007;66: 351Ð7.
56.Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, Richards A, Rauz S, Emery P. Reduction of fatigue in SjogrenÕs syndrome with rituximab: results of a randomised, double-blind, placebo controlled pilot study. Ann Rheum Dis. 2008 Nov;67:1541Ð4.
57.Meijer J, Vissink A, Meiners PM, Spijkervet FKL, Kallenberg CGM, Bootsma H. Rituximab treatment in primary SjšgrenÕs syndrome: a doubleblind placebo controlled trial. Arthritis Rheum. 2008;56:S430 (abstract 713).
58.Steinfeld SD, Tant L, Burmester GR, et al. Epratuzumab (humanised anti-CD22 antibody) in primary SjšgrenÕs syndrome: an open-label phase I/II study. Arthritis Res Ther. 2006;8(4):R129.
59.Gatumu MK, Skarstein K, Papandile A, Browning JL, Fava RA, Bolstad AI. Blockade of lymphotoxinbeta receptor signaling reduces aspects of SjšgrenÕs syndrome in salivary glands of non-obese diabetic mice. Arthritis Res Ther. 2009;11:R24. Epub 2009 Feb 18.
60.Kok MR, Yamano S, Lodde BM, Wang J, Couwenhoven RI, Yakar S, Voutetakis A, Leroith D, Schmidt M, AÞone S, Pillemer SR, Tsutsui MT, Tak PP, Chiorini JA, Baum BJ. Local adenoassociated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of SjšgrenÕs syndrome. Hum Gene Ther. 2003;14: 1605Ð18.
61.Lodde BM, Mineshiba F, Wang J, Cotrim AP, AÞone S, Tak PP, Baum BJ. Effect of human vasoactive intestinal peptide gene transfer in a murine model of SjogrenÕs syndrome. Ann Rheum Dis. 2006 Feb;65:195Ð200.
62.Harner KC, Jackson LW, Drabick JJ. Normalization of anticardiolipin antibodies following rituximab therapy for marginal zone lymphoma in a patient
33 Looking into the Future—Emerging Therapies Based on Pathogenesis |
481 |
|
|
with SjogrenÕs syndrome. Rheumatology. 2004;43: 1309Ð10.
63.Ramos-Casals M, L—pez-Guillermo A, Brito-Zer—n P, Cervera R, Font J, SS-HCV Study Group. Treatment of B-cell lymphoma with rituximab in two patients with SjšgrenÕs syndrome associated with hepatitis C virus infection. Lupus 2004;13:969Ð71.
64.Gottenberg JE, Guillevin L, Lambotte O, Combe B, Allanore Y, Cantagrel A, Larroche C, Soubrier M, Bouillet L, Dougados M, Fain O, Farge D, Kyndt X, Lortholary O, Masson C, Moura B, Remy P, Thomas T, Wendling D, Anaya JM, Sibilia J, Mariette X, Club Rheumatismes et Inßammation (CRI). Tolerance and short term efÞcacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis. 2005;64:913Ð20.
65. Ahmadi-Simab K, Lamprecht P, Nšlle B, Ai M, Gross WL. Successful treatment of refractory anterior scleritis in primary SjogrenÕs syndrome with rituximab. Ann Rheum Dis. 2005;64: 1087Ð8.
66.Ring T, Kallenbach M, Praetorius J, Nielsen S, Melgaard B. Successful treatment of a patient with primary SjšgrenÕs syndrome with rituximab. Clin Rheumatol. 2006 Nov;25(6):891Ð4. Epub 2005 Nov 8.
67.St. Clair E, Levesque MC, Luning Prak N, Vivino FB, Alappatt C, Wallace D, Wedgwood J, Cohen P. Rituximab therapy for primary SjšgrenÕs syndrome (pSS): an open-label trial. Arthritis Rheum. 2007;56:S449 (abstract 1102).