Do autoantigens define autoimmunity or <i>vice versa</i>?

Eisenberg, Robert A.

doi:10.1002/eji.200425888

Cited by 8 publications

(3 citation statements)

References 26 publications

(24 reference statements)

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“…On the other hand, there exists the possibility that there simply is no single antigen or epitope that is specific for RA but a pattern of several autoantigens that is characteristic for the disease and might even be distinct in different individuals (reviewed in Refs. [21,22]). Even though it is the main function of B-cells, the production of antibodies is only one aspect of how B-cells can influence the course of an inflammatory reaction.…”

Section: Antibody Productionmentioning

confidence: 97%

B-cell involvement in the pathogenesis of RA–is there a contribution of the sympathetic nervous system?

Pongratz

Straub

2007

Immunol Res

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The pathogenesis of rheumatoid arthritis (RA), the most common rheumatic disease, is still an unsolved puzzle. For many years, T-cells were the main focus of research, but recently, the B-cell drew more and more attention not least, due to the observation in humans that the anti-CD20 antibody Retuximab, which selectively depletes subsets of B-cells, lessens disease symptoms. A second novel approach to understand pathomechanisms that contribute to the development and progression of arthritis focuses on the sympathetic nervous system, which is known to moderate the function of immune cells, e.g., the B-cell, and therefore, is tied into a complex neuroimmune network that influences the course of the disease. This review first discusses current research that shows the significance of B-cells in the pathogenesis of RA. It then gives a short review of knowledge regarding the role of the sympathetic nervous system (1) in RA pathogenesis and (2) in modulating B-cell responses. Finally, the hypothesis is introduced that the sympathetic nervous system via modulating B-cell function, e.g., antibody production, influences the development and progression of RA.

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Section: Antibody Productionmentioning

confidence: 97%

B-cell involvement in the pathogenesis of RA–is there a contribution of the sympathetic nervous system?

Pongratz

Straub

2007

Immunol Res

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“…Effective treatment with rituximab results in complete depletion of B cells from the peripheral blood. B cell depletion from the bone marrow, spleen, and lymph nodes is not well documented and is probably less complete than from the blood (9)(10)(11). Insufficient depletion of B cells from peripheral tissues has been observed in mice (12,13), whereas RA patients demonstrate thorough depletion, and a few SLE patients show incomplete depletion (14).…”

mentioning

confidence: 99%

“…B cell ontogeny is marked by CD20 surface expression on all B cell lineages, from the pre-B cell stage to the later stages of differentiation. Early pro-B cells and terminally differentiated plasma cells do not express CD20 on their surface and, thus, are not directly targeted by the therapy (11). Following rituximab therapy, undepleted pro-B cells further differentiate and gradually repopulate the periphery with newly formed B cells.…”

mentioning

confidence: 99%

Modulation of molecular imprints in the antigen‐experienced B cell repertoire by rituximab

Palanichamy¹,

Roll²,

Theiss³

et al. 2008

Arthritis & Rheumatism

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Objective. Transient B cell depletion by rituximab has recently gained more importance in the treatment of rheumatic disorders. Nevertheless, little is known about the reemerging B cells. We analyzed dynamic changes in the repopulating B cells, particularly the postswitch B cells, and studied the mutational patterns of Ig genes in antigen-experienced B cells.Methods. Five patients with active rheumatoid arthritis (RA) were treated with rituximab. In 3 patients, B cell receptor (BCR) gene analysis was performed before treatment and during B cell recovery using genomic DNA. In 2 patients, B cell subsets were studied during the early recovery phase using single-cell technology. For comparison, immunophenotyping of B cell subsets was performed.Results. Early B cell recovery was marked by a relatively expanded population of highly mutated B cells, which were correlated with B cells with a plasmablast phenotype on comparative immunophenotyping. Analysis of the mutational pattern in these cells revealed increased RGYW/WRCY (where R ‫؍‬ A/G, Y ‫؍‬ C/T, and W ‫؍‬ A/T) hotspot targeting (44% before rituximab versus 59% after) and elevated ratios of replacement to silent mutations within the complementarity-determining regions in Ig genes (1.87 before rituximab versus 2.67 after; P < 0.0025).Conclusion. Our findings show that rituximab leads to qualitative changes in the imprints of highly mutated, antigen-experienced BCRs, representing the result of selection, whereas molecular processes such as Ig V rearrangements are not affected by this treatment.

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Anti-cancer immune response mechanisms in neoadjuvant and targeted therapy

et al. 2011

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Several studies suggest that the progression of malignant tumors as well as the response to chemotherapy and targeted therapy is critically dependent on the immunological parameters that are derived from the host immune system as well as a modulation of the immune system by therapeutic antibodies. It has been shown for many tumor types that the presence of a lymphocytic infiltrate in different types of cancers is a positive factor for clinical outcome and that the response to neoadjuvant chemotherapy is increased in a tumor with a prominent pretherapeutic infiltrate. Furthermore, new targeted therapies in breast cancer, such as trastuzumab, as well as in hematological malignancies, such as rituximab and alemtuzumab, have been shown to interact with immunological pathways, and this interaction is critical for response and clinical outcome. In neoplasms of lymphoid and hematopoietic tissues, targeted therapies not only reduce toxic effects on normal tissues but also lead to modulations of the immune system depending on the target molecule, its physiological function and cellular distribution. This review gives an overview on clinical data on response to classical chemotherapy as well as molecular targeted therapy and its interaction with the immune system.

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Do autoantigens define autoimmunity or vice versa?

Cited by 8 publications

References 26 publications

B-cell involvement in the pathogenesis of RA–is there a contribution of the sympathetic nervous system?

B-cell involvement in the pathogenesis of RA–is there a contribution of the sympathetic nervous system?

Modulation of molecular imprints in the antigen‐experienced B cell repertoire by rituximab

Anti-cancer immune response mechanisms in neoadjuvant and targeted therapy

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