Abstract
Before the use of rituximab, the strongest accepted evidence for an association between B-cells and rheumatoid arthritis (RA) was that clinical disease was associated with serum autoantibodies. The ability to remove B-cells with rituximab has also revealed the relative importance of the different immunological parameters that underlie the clinical symptoms of RA. First, seropositive patients have a significantly more predictable and favorable clinical response to rituximab than seronegative patients. Second, the kinetics of the clinical response, with a delay of weeks or months after depletion, suggest that it is a B-cell product (autoantibody) and not B-cells per se that need to be reduced for remission to occur. Third, removal of B-cells from joints may not be closely associated with clinical improvement, although maintenance of plasma cell counts in joints has been associated with poorer responses. The requirement of ‘new’ B-cells generated from the bone marrow for relapse to occur suggests that selection of autoreactive B-cell clones in the periphery may also be necessary for their survival and differentiation into autoantibody-producing cells. The initial hypothesis suggested that the autoimmune response underlying the pathogenesis of RA was self-sustaining. This would seem to be confirmed, as relapse inevitably follows a variable period of reduced clinical symptoms induced by rituximab. In addition, a dominant role for autoantibodies seems to have strong support from clinical practice. In addition to their possible role in the pathogenesis of RA in the form of immune complexes, further investigation is necessary to determine whether autoantibodies contribute to perpetuation of changes in central B-cell tolerance in these patients.
Keywords: Rheumatoid arthritis, b-cells. Rituximab.
Current Pharmaceutical Design
Title:Response to Rituximab: Has the Original Hypothesis Been Confirmed?
Volume: 21 Issue: 2
Author(s): Geraldine Cambridge and Inmaculada De La Torre
Affiliation:
Keywords: Rheumatoid arthritis, b-cells. Rituximab.
Abstract: Before the use of rituximab, the strongest accepted evidence for an association between B-cells and rheumatoid arthritis (RA) was that clinical disease was associated with serum autoantibodies. The ability to remove B-cells with rituximab has also revealed the relative importance of the different immunological parameters that underlie the clinical symptoms of RA. First, seropositive patients have a significantly more predictable and favorable clinical response to rituximab than seronegative patients. Second, the kinetics of the clinical response, with a delay of weeks or months after depletion, suggest that it is a B-cell product (autoantibody) and not B-cells per se that need to be reduced for remission to occur. Third, removal of B-cells from joints may not be closely associated with clinical improvement, although maintenance of plasma cell counts in joints has been associated with poorer responses. The requirement of ‘new’ B-cells generated from the bone marrow for relapse to occur suggests that selection of autoreactive B-cell clones in the periphery may also be necessary for their survival and differentiation into autoantibody-producing cells. The initial hypothesis suggested that the autoimmune response underlying the pathogenesis of RA was self-sustaining. This would seem to be confirmed, as relapse inevitably follows a variable period of reduced clinical symptoms induced by rituximab. In addition, a dominant role for autoantibodies seems to have strong support from clinical practice. In addition to their possible role in the pathogenesis of RA in the form of immune complexes, further investigation is necessary to determine whether autoantibodies contribute to perpetuation of changes in central B-cell tolerance in these patients.
Export Options
About this article
Cite this article as:
Cambridge Geraldine and De La Torre Inmaculada, Response to Rituximab: Has the Original Hypothesis Been Confirmed?, Current Pharmaceutical Design 2015; 21 (2) . https://dx.doi.org/10.2174/1381612820666140825123950
DOI https://dx.doi.org/10.2174/1381612820666140825123950 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Ectopic Thyroid Gland: Description of a Case and Review of the Literature
Endocrine, Metabolic & Immune Disorders - Drug Targets Integrase Strand Transfer Inhibitors and the Emergence of Immune Reconstitution Inflammatory Syndrome (IRIS)
Current HIV Research Antitumor and Antiviral Activity of Pentacyclic Triterpenes
Mini-Reviews in Organic Chemistry Electroporation in DNA Vaccination Protocols Against Cancer
Current Drug Metabolism Crucial Parameters Responsible for Carbon Nanotubes Toxicity
Current Nanoscience Protease Inhibitors with Antileishmanial Activity
Current Enzyme Inhibition Anti-Inflammatory and Antioxidant Properties of Piper Species: A Perspective from Screening to Molecular Mechanisms
Current Topics in Medicinal Chemistry Engineered Biosynthesis of Medicinally Important Plant Natural Products in Microorganisms
Current Topics in Medicinal Chemistry Anti-Tumour Activity of Glycodendrimer Nanoparticles in a Subcutaneous MEC-1 Xenograft Model of Human Chronic Lymphocytic Leukemia
Anti-Cancer Agents in Medicinal Chemistry Histone Deacetylase Inhibitors: Therapeutic Agents and Research Tools for Deciphering Motor Neuron Diseases
Current Medicinal Chemistry Brutons Tyrosine Kinase as a New Therapeutic Target
Anti-Cancer Agents in Medicinal Chemistry Dietary and Plant Polyphenols Exert Neuroprotective Effects and Improve Cognitive Function in Cerebral Ischemia
Recent Patents on Food, Nutrition & Agriculture Protein Interaction Domains: Structural Features and Drug Discovery Applications (Part 2)
Current Medicinal Chemistry Drug Discovery in Ovarian Cancer
Recent Patents on Anti-Cancer Drug Discovery New Opportunities to Treat the T315I-Bcr-Abl Mutant in Chronic Myeloid Leukaemia: Tyrosine Kinase Inhibitors and Molecules that Act by Alternative Mechanisms
Current Medicinal Chemistry Regulation of the Immune Response by Natural IgM: Lessons from Warm Autoimmune Hemolytic Anemia
Current Pharmaceutical Design Novel and Emerging Drugs for Acute Myeloid Leukemia
Current Cancer Drug Targets Enhanced Activity of pSTAT-3 Ser-727 in Functional Endothelial Cells Under Calcifying Conditions
Current Chemical Biology Hybrid PET/MRI for In Vivo Imaging of Cancer: Current Clinical Experiences and Recent Advances
Current Medical Imaging Antibodies As Promising Novel Neuroprotective Agents in the Central Nervous System Injuries
Central Nervous System Agents in Medicinal Chemistry