Objective. To investigate whether the incidence of secondary hypogammaglobulinaemia in patients with RA following rituximab was related to patterns of B-cell return and relapse. Methods. CD19 + B-cell and serum immunoglobulin (sIg) determinations were done every 2 or 3 months in 137 consecutive patients treated with one or more courses of rituximab-based B-cell depletion therapy. The pattern of B-cell return, either concordant or discordant with relapse, was also recorded. Results. There were 119 responders. Before treatment, three patients had low IgM and four had low IgG. After the first cycle, low IgM or IgG was present in 9.2% (11/119) and 11.8% (14/119) of the patients, respectively, increasing to 38.8% (8/18) and 22.2% (4/18) after five cycles. The mean percent maximum sIg decrease/cycle was relatively constant. The CD19 + B-cell count at repopulation was not correlated with immunoglobulin (Ig) levels after each cycle. Patients discordant for B-cell return and relapse developed significantly lower serum IgM and more low IgM episodes than concordant patients (P < 0.05). Conclusion. Patients with lower baseline sIg levels tended to develop persistent IgM and IgG hypogammaglobulinaemia, resulting from an accumulation of incremental decreases after repeat cycles. This was not due to lower numbers of returning B cells in those developing low sIgs. The association of low IgM in patients with a discordant pattern of relapse suggests that underlying defects in B cells relating to survival and maturation into Ig-secreting cells, as well as attrition of IgG plasma cells may be contributing to low sIg levels in some patients.
Immunological memory is a cornerstone of the defence against pathogens, ensuring that repeated exposures to an antigen produce faster, more robust responses. Might chronic autoimmune diseases likewise owe their persistence and reactivation to an equivalent cellular memory? In this Review, the authors summarize the current understanding of long-lived autoreactive plasma cells, including how they are generated and where they reside, and explore their implications for the treatment of autoimmune di...
Objectives To examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab. Patients and Methods BAFF-R expression on B-cell subsets was determined in normal controls (NC; n=11), active patients with RA pre-rituximab (pre-RX; n=15), relapsing patients either concordant for B-cell repopulation (C-R, n=13) or discordant, with relapse m...
Summary: The advent of therapies that specifically target the B-lymphocyte lineage in human disease has rejuvenated interest in the mechanistic biology by which B cells mediate autoimmunity. B cells have a multitude of effector functions including production of self-reactive antibodies, ability to present antigen to T lymphocytes in the context of costimulation, involvement in generation and maintenance of neo-organogenesis at sites of disease, and opposing function through production of both im...
Objective. To evaluate the longterm safety of rituximab in clinical trials in patients with rheumatoid arthritis (RA). Methods. Pooled analysis of safety data, including adverse events (AE) and infections, from patients treated with rituximab in combination with methotrexate in a global clinical trial program. Results. A total of 2578 patients with RA received at least 1 course of rituximab. Safety analyses were based on 5013 patient-years of rituximab exposure. The most frequent AE was infusion...
Rituximab, an anti-CD20 chimeric antibody, is the first monoclonal agent to be used in the therapy of cancer. It has been hailed as one of the most important therapeutic developments of the decade. While transient peripheral B cell depletion is common after rituximab therapy, immunoglobulin levels are generally not affected. This is because CD20 is expressed on pre-B and mature B lymphocytes but not on stem cells or plasma cells. Two adult patients with pre-existing primary antibody deficiency w...
Objectives: To analyse whether persistence of synovial B lineage cells and lack of clinical response to rituximab treatment in patients with rheumatoid arthritis (RA) are associated with low rituximab serum levels and anti-rituximab antibody (ARA) formation. Methods: Fifty-eight patients with RA were treated with rituximab. The clinical response was determined 24 weeks after each treatment course using the Disease Activity Score evaluated in 28 joints (DAS28) and EULAR response criteria. Rituxim...
Introduction Reconstitution of peripheral blood (PB) B cells after therapeutic depletion with the chimeric anti-CD20 antibody rituximab (RTX) mimics lymphatic ontogeny. In this situation, the repletion kinetics and migratory properties of distinct developmental B-cell stages and their correlation to disease activity might facilitate our understanding of innate and adaptive B-cell functions in rheumatoid arthritis (RA).
Objective In rheumatoid arthritis (RA), B cell depletion occurs in all patients treated with rituximab, but the clinical responses to rituximab are variable. A highly sensitive assay was used to test the hypothesis that B cell depletion is variable, and that incomplete depletion leads to a poorer outcome. Methods Sixty patients with active RA unresponsive to anti–tumor necrosis factor agents received two 1-gram infusions of rituximab. B cell numbers were measured by highly sensitive flow cytomet...
Hypogammaglobulinemia is a major adverse event after rituximab treatment; however, the precise incidence and risk factors are unclear in complicated steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) patients. This was a single-center, retrospective, observational study. Patients who received a single dose of rituximab for complicated SDNS or FRNS between February 2007 and May 2019 were enrolled. Serum IgG levels were plotted, and their trends were evaluated after rituximab...
Secondary hypogammaglobulinemia (SHG) is characterized by a decrease in total serum immunoglobulin (Ig) levels and can lead to immunodeficiency associated with recurrent and severe infections and is a common complication of chronic lymphocytic leukaemia (CLL). SHG also increases with the treatment of CLL. Ibrutinib is one of these treatments and acts by inhibiting bruton tyrosine kinase. Twenty-seven patients with relapsed/refractory (R/R) CLL who received ibrutinib monotherapy were included. Ig...
#2A. G. Vakrakou(UoA: National and Kapodistrian University of Athens)
Last. Panos Stathopoulos(UoA: National and Kapodistrian University of Athens)H-Index: 11
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As B cells differentiate into antibody-secreting cells (ASCs), short-lived plasmablasts (SLPBs) are produced by a primary extrafollicular response, followed by the generation of memory B cells and long-lived plasma cells (LLPCs) in germinal centers (GCs). Generation of IgG4 antibodies is T helper type 2 (Th2) and IL-4, -13, and -10-driven and can occur parallel to IgE, in response to chronic stimulation by allergens and helminths. Although IgG4 antibodies are non-crosslinking and have limited ab...
#2Ilker Ilhanli(OMU: Ondokuz Mayıs University)H-Index: 4
Abstract Aim of the work To evaluate the 6-month treatment responses to low dose rituximab (LDR) compared to standard dose rituximab (SDR) in rheumatoid arthritis (RA) patients whose treatments were disrupted due to the pandemic with increased disease activity and to examine the effect of LDR treatment on serum immunoglobulin (Ig) levels. Patients and methods Records were retrospectively analysed for 80 patients on SDR not admitted to the hospital due to fear of infection during pandemic, with i...
Objectives Rituximab (RTX) use in the treatment of RA can be complicated by decrease in IgG, IgM or IgA levels (hypogammaglobulinemia-HGG). The aim of this study was to define the frequency of HGG in RA patients treated with RTX and to identify associations between its occurrence and patients' characteristics, disease outcomes and serious infections rate. Methods RA patients treated with RTX in two rheumatology centers from January 2007 to January 2020 were retrospectively examined. Demographica...
Immunoglobulins and antibodies to immunoglobulins (autoimmunoglobulins) have been identified to be implicated in the pathogenesis of rheumatoid arthritis (RA). Immunoglobulin deficiencies have been suggested to account for the increased risk of infections in RA patients. This study was carried out to determine the prevalence of immunoglobulin deficiencies in patients with RA and the identification of putative contributing factors. Immunoglobulin levels in blood samples of patients with rheumatoi...
BACKGROUND Ocrelizumab safety outcomes have been well evaluated in clinical trials and open-label extension (OLE) studies. However, risk factors for infection in patients with multiple sclerosis (MS) receiving ocrelizumab have not been extensively studied in the real-world setting. OBJECTIVE The aim of this study was to examine factors determining risk of self-reported infections and antimicrobial use in patients receiving ocrelizumab for MS. METHODS A retrospective, observational cohort study w...
B-cell targeted therapies, such as rituximab (RTX), are used widely in autoimmune rheumatic diseases (AIRD). RTX can cause hypogammaglobulinemia and predispose patients to infections. Herein, we asked whether the underlying diagnosis influences the risk for hypogammaglobulinemia in patients treated with RTX. All patients who received RTX infusions and carried a diagnosis of rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), or connective tissue disease (CTD) were included in this singl...
Abstract Objectives Ocrelizumab (OCR) is a humanized monoclonal antibody targeting CD20 antigen exposed on B cells surface. Kinetic of B-cells repopulation after depletion therapy shows high intra and inter-individual variability. The aim of this study was to explore the influence of Body Mass Index (BMI) on kinetic of B-cell repopulation after treatment with OCR and on treatment response. Methods 108 Multiple Sclerosis (MS) patients were enrolled at the time of the first dose of OCR administrat...
