New Insights into Rheumatoid Arthritis, An Issue of Rheumatic Disease Clinics

David A. Fox

Description

There are numerous monographs devoted to rheumatoid arthritis. What sets this issue apart is that it keeps an eye to the future. Topics explored include measurement of RA disease activity today and in the future; epidemiology of RA – implications for prevention and risk assessment; genes that predispose to RA – relevance to current and future therapeutic strategies; multiple kinases – assessment of the best targets in treating RA; assessment, prevention and treatment of cardiovascular morbidity in RA; mechanistic insights and approaches to prevention of bone damage in RA; cell-cell interactions in RA synovium as potential new targets for treatment; alternative strategies for modulating the function of B lymphocytes in RA; innate immunity in RA; ascertainment and management of preclinical RA.

Sujets

• Medical
• Médecine
• Rheumatology

Informations

• Publié par: Saunders
• Date de parution: 29 juin 2010
• Nombre de lectures: 0
• EAN13: 9781455700646
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Rheumatic Disease Clinics of NA , Vol. 36, No. 2, May 2010
ISSN: 0889-857X
doi: 10.1016/S0889-857X(10)00030-X

Contributors
Rheumatic Disease Clinics of NA
New Insights into Rheumatoid Arthritis
David A. Fox
Division of Rheumatology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
ISSN  0889-857X
Volume 36 • Number 2 • May 2010

Contents
Cover
Contributors
Forthcoming Issues
Preface
Preclinical Rheumatoid Arthritis: Identification, Evaluation, and Future Directions for Investigation
How Should Rheumatoid Arthritis Disease Activity Be Measured Today and in the Future in Clinical Care?
Leveraging Human Genetics to Develop Future Therapeutic Strategies in Rheumatoid Arthritis
Innate Immunity and Rheumatoid Arthritis
Immune Aging and Rheumatoid Arthritis
Cell-cell Interactions in Rheumatoid Arthritis Synovium
B Cell Therapies for Rheumatoid Arthritis: Beyond B cell Depletion
Targeting IL-17 and Th17 Cells in Rheumatoid Arthritis
A Multitude of Kinases—Which are the Best Targets in Treating Rheumatoid Arthritis?
Bone Damage in Rheumatoid Arthritis: Mechanistic Insights and Approaches to Prevention
Cardiovascular Complications of Rheumatoid Arthritis: Assessment, Prevention, and Treatment
Index
Rheumatic Disease Clinics of NA , Vol. 36, No. 2, May 2010
ISSN: 0889-857X
doi: 10.1016/S0889-857X(10)00032-3

Forthcoming Issues
Rheumatic Disease Clinics of NA , Vol. 36, No. 2, May 2010
ISSN: 0889-857X
doi: 10.1016/j.rdc.2010.03.005

Preface
Rheumatoid Arthritis—Halfway There

David A. Fox, MD
Division of Rheumatology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
E-mail address: [e-mail]


David A. Fox, MD Guest Editor
Progress in the understanding and treatment of rheumatoid arthritis (RA) over the past three decades has been spectacular. Immunologic and molecular insights have directly led to a transformation of the treatment of RA, and the impact of these advances has resonated well beyond the field of rheumatology.
Despite these accomplishments, most of which are relevant specifically to the articular manifestations of RA, many challenges remain. We still do not know the cause of RA and lack a cure or well-validated prevention strategies. Thus, the three critical goals for any disease—cause, cure, and prevention—remain unattained. Even more unsettling, it seems that the undeniably impressive leaps forward in the treatment of RA may not yet be mitigating the survival disadvantage that this complex disease confers on its victims.
It is with these considerations in mind—remarkable progress as well as daunting challenges—that this issue of Rheumatic Disease Clinics of North America has been constructed. The authors of each article have been asked not only to consider the current state of the art but also to assess how the latest advances might affect treatment in the future. It is our hope that these links will prove interesting and compelling for clinical rheumatologists.
The article topics cover a wide range of subjects that reflect the spectrum of important issues in understanding, assessing, and managing RA. An article on preclinical RA integrates epidemiology, biomarkers, and aspects of pathogenesis to provide a conceptual basis for prevention strategies. An article on measurement of disease activity addresses issues that are critical to clinical research and patient care. The article on RA genetics updates and clarifies recent and rapid progress in this field. Articles that tie the pathophysiology of RA to current and future approaches to treatment focus on innate immunity, cellular senescence, Th17 cells, bone biology, and synovial cell interactions. Additional targets for therapeutics are considered in the articles on B cells and on kinases. The increasingly important topic of cardiovascular complications of RA is addressed in a separate article. Important topics have been omitted due to space constraints, but most of these are well reviewed in other recent publications.
No attempt has been made to reconcile or homogenize the diverse perspectives that individual authors have brought to their assigned topics. Instead, contrasting and well-supported points of view are presented that reflect the knowledge and judgment of the experts who have generously agreed to contribute to this issue. At a point in time when we are arguably approximately halfway towards what needs to be accomplished for patients with RA, it is my hope that this volume will help clarify an agenda of questions that need to be asked and answered in the years ahead.
Rheumatic Disease Clinics of NA , Vol. 36, No. 2, May 2010
ISSN: 0889-857X
doi: 10.1016/j.rdc.2010.02.001

Preclinical Rheumatoid Arthritis: Identification, Evaluation, and Future Directions for Investigation

Kevin D. Deane, MD a , * , Jill M. Norris, MPH, PhD b , V. Michael Holers, MD a
a Division of Rheumatology, University of Colorado School of Medicine, 1775 Aurora Court, Mail Stop B-115, Aurora, CO 80045, USA
b Department of Epidemiology, Colorado School of Public Health, University of Colorado, 13001 East 17th Place, Aurora, CO 80045, USA
* Corresponding author.
E-mail address: [e-mail]

Abstract
Rheumatoid arthritis (RA) likely develops in several phases, beginning with genetic risk, followed by asymptomatic autoimmunity, then finally, clinically apparent disease. Investigating the phases of disease that exist prior to the onset of symptoms (ie, the preclinical period of RA) will lead to understanding of the important relationships between genetic and environmental factors that may lead to disease, as well as allow for the development of predictive models for disease, and ultimately preventive strategies for RA.

Keywords
• Rheumatoid arthritis • Preclinical period • Anticyclic citrullinated peptide antibodies


“When the rheumatic poison is in the system, any disturbing circumstance, even of temporary duration, such as over fatigue, anxiety, grief or anger, by rendering the system more susceptible of its influence, may prove the accidental or exciting cause of the disease”


Henry William Fuller in “On Rheumatism, Rheumatic Gout, and Sciatica” Publishers: Samuel S & William Wood, New York, 1854.
The discovery of genetic and environmental factors associated with rheumatoid arthritis (RA), and elevations in autoantibodies and inflammatory markers prior to the onset of symptomatic disease, coupled with similar findings in other autoimmune diseases including type 1 diabetes mellitus (T1DM), has led to the creation of a shared model of autoimmune disease development. In this model, the development of RA follows a natural history divided into phases wherein genetic and environmental interactions initially lead to a period of asymptomatic autoimmunity, evidenced by the presence of RA-related autoantibodies, that later evolves into clinically apparent disease. It is the initial phases of risk and asymptomatic autoimmunity that encompass “preclinical” RA.
To understand the genetic and environmental influences that are important to the evolution of RA, as well as develop predictive models and preventive strategies for future symptomatic disease, this preclinical period must be investigated. Herein are discussed the following issues related to preclinical RA: (1) what is known about the preclinical development of autoimmunity and inflammation in RA as well as other autoimmune diseases that may follow a similar model of development as RA, (2) how RA development can be modeled based on studies in preclinical RA and other autoimmune diseases, (3) practical issues related to the challenge of defining for research studies “preclinical” RA, as compared with clinically apparent disease, and (4) what aspects of RA evolution including genetic and environmental influences, and predictive and preventive models, could be addressed in studies of the preclinical period. Finally, potential methodologies and areas of focus going forward for research into preclinical RA are discussed.

Part 1. Autoantibodies and inflammation in preclinical rheumatoid arthritis as well as other autoimmune diseases

Studies of Preclinical Rheumatoid Arthritis
Multiple studies have shown that RA-related autoantibodies are present years before the diagnosis of RA ( Table 1 ). 1 - 11 del Puente and colleagues, 1 who investigated RA in the Pima Indians in the Southwestern United States, showed that rheumatoid factor was present before the onset of clinically apparent RA. Aho and colleagues, 2, 12 - 14 who investigated preclinical RA in Finland using a biobank of stored prediagnosis samples, and Jonsson and colleagues, 15 who used Icelandic biobank samples, also demonstrated that rheumatoid factor (RF) (by various methodologies) was present prior to the onset of clinically apparent RA. Also, in a prospective study of initially healthy family members of patients with RA, Silman and colleagues 11 showed that the presence of RF preceded the onset of clinically apparent RA.

Table 1 Summary of selected studies of preclinical rheumatoid arthritis (RA)


Later studies also showed preclinical RA positivity for RF, as well as positivity for the highly RA-specific a ntibodies to c itrullinated p rotein a ntigens (ACPAs). Again using a Finnish biobank, Aho and colleagues 3, 4 demonstrated preclinical RA positivity of antikeratin (AKA) and antiperinuclear factor (APF) antibodies, and antifilla