Current perspective on rituximab in rheumatic diseases

Schioppo, Tommaso; Ingegnoli, Francesca

doi:10.2147/dddt.s139248

Cited by 85 publications

(57 citation statements)

References 113 publications

(82 reference statements)

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“…The B‐cell depletion approach is an approved therapy for lymphoma patients and for some autoimmune diseases (Salles et al, ; Schioppo & Ingegnoli, ). A recent article has shown that B‐cell depletion in systemic sclerosis patients not only promotes remission but also temporarily reverses the disease‐restricted B‐cell repertoire due to new B‐cell generation (Bourcy, Dekker, Davis, & Nicolls, ).…”

Section: Discussionmentioning

confidence: 99%

Depletion of B cells rejuvenates the peripheral B‐cell compartment but is insufficient to restore immune competence in aging

et al. 2019

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Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B‐cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B‐cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B‐cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B‐cell compartments. B‐cell depletion in old mice resulted in rejuvenated B‐cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a "young"‐like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B‐cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in "dirty" environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a "young"‐like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B‐cell compartment in aging, through B‐cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population.

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Section: Discussionmentioning

confidence: 99%

Depletion of B cells rejuvenates the peripheral B‐cell compartment but is insufficient to restore immune competence in aging

et al. 2019

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“…Because of the suspected causal role of B lymphocytes in the pathogenesis of SS, rituximab (a monoclonal antibody that depletes B cells) has been used, with anecdotal responses. 305,306 Data on the effect of rituximab in pSS are mixed. Gottenberg et al prospectively followed up 78 patients with systemic involvement of pSS in the AutoImmune and Rituximab (AIR) registry who were treated with rituximab.…”

Section: Rituximabmentioning

confidence: 99%

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

Chung

Wilgus

Fishbein

et al. 2019

Semin Respir Crit Care Med

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Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by mononuclear cells (principally lymphocytes) infiltrating exocrine glands (e.g., salivary and lacrimal glands), leading to destruction of exocrine epithelial cells and dryness of mucosal surfaces. Cardinal symptoms are dry eyes (xerophthalmia) and dry mouth (xerostomia). Extraglandular sites are affected in 30 to 40% of cases of SS (particularly neurological, kidneys, skin, and lungs). B cell hyperactivity, autoantibody production, and hypergammaglobulinemia are cardinal features of SS. Primary SS is not associated with other autoimmune diseases. However, SS can complicate diverse autoimmune disorders (particularly systemic lupus erythematosus, rheumatoid arthritis, and scleroderma); this form is termed “secondary SS.” Pulmonary involvement is usually not a dominant feature of SS, but may be severe in some cases. In this review, we discuss specific tracheal, bronchiolar, and pulmonary complications of SS including xerotrachea, bronchiolitis, bronchiectasis, interstitial lung disease, nonspecific interstitial pneumonia, usual interstitial pneumonia, lymphoid interstitial pneumonia, organizing pneumonia, acute fibrinous and organizing pneumonia, pulmonary cysts, pleural effusions, pulmonary amyloidosis, and bronchus- or lung-associated lymphomas.

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“…RTX is combined with several chemotherapies for treating B cell lymphoma and is used alone to treat autoimmune diseases such as rheumatism. Clinical trials have already provided evidence on the safety of RTX [1][2][3][4] .…”

Section: Introductionmentioning

confidence: 99%

A Synergistic Antitumor Effect of Rituximab and Gamma Interferon Combined Therapy on Human CD20＋ B-Cell Lymphoma Cells

Kamijo¹,

Tsuchiya

Gocho³

et al. 2018

Showa Univ J Med Sci

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Rituximab RTX is an anti-CD20 human-mouse chimeric monoclonal antibody that exhibits antibody-dependent, cell-mediated cytotoxicity and complementdependent cytotoxicity, resulting in an antitumor effect with immune cells or complement. RTX is approved for the treatment of many diseases including B cell lymphoma and rheumatoid arthritis. We examined whether combined RTX and gamma interferon IFN therapy provides a higher antitumor effect than RTX single therapy using B-cell lymphoma cells. In addition, we investigated the mechanisms underlying the antitumor effect. We treated tumor-derived cell lines with RTX alone, IFN alone, or a combination of RTX and IFN RTX-IFN. Untreated cells served as controls. We experimentally examined in vitro cell proliferation, conducted apoptosis and cell cycle assays, performed Western blotting to identify changes in the levels of proteins related to the cell cycle, and investigated tumor growth in a mouse xenograft experiment. Cell proliferation experiments indicated that RTX or IFN alone did not signi cantly suppress cell growth compared with the control, whereas treatment with RTX-IFN signi cantly suppressed cell proliferation. In vivo mouse experiments also showed that the administration of RTX-IFN signi cantly suppressed tumor growth compared to the single therapies. Some tumors in mice treated with RTX-IFN were completely resolved. The cell cycle assays revealed a signi cantly increased rate of cells in the G0/G1 phase following treatment with RTX-IFN compared with the other groups, and the levels of p27 kip1 increased and the levels of cyclin E and Cdk 2 decreased in cells treated with RTX-IFN. Our ndings suggested that RTX-IFN combined therapy directly affects cells by arresting the cell cycle at the G1/S checkpoint and had a synergistic antitumor effect compared to RTX single treatment of B-cell lymphomas. This combined therapy may change the mortality rate for B-cell lymphomas.

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Current perspective on rituximab in rheumatic diseases

Cited by 85 publications

References 113 publications

Depletion of B cells rejuvenates the peripheral B‐cell compartment but is insufficient to restore immune competence in aging

Depletion of B cells rejuvenates the peripheral B‐cell compartment but is insufficient to restore immune competence in aging

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

A Synergistic Antitumor Effect of Rituximab and Gamma Interferon Combined Therapy on Human CD20＋ B-Cell Lymphoma Cells

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