The effect of B-cell depletion therapy on serological evidence of B-cell and plasmablast activation in patients with rheumatoid arthritis over multiple cycles of rituximab treatment

Cambridge, G; Perry, Hayley; Nogueira, Léonor; Serre, Guy; Parsons, HM; Torre, Inmaculada de la; Dickson, Marion C.; Leandro, Maria; Edwards, J. C. W.

doi:10.1016/j.jaut.2013.12.002

Cited by 74 publications

(69 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Differences in patterns of fluctuations in anti‐dsDNA antibodies between patients implied a variable contribution from anti‐dsDNA committed B cell clones (CD20+) sensitive to B cell depletion, as well as from long‐lived (IgG) plasma cells (CD20−) 53. Autoantibody‐committed B cells are often preferentially removed by rituximab, as has also been shown in patients with RA 39, 54. A significant proportion of patients lost seropositivity to dsDNA at long‐term followup; however, there was little overall decrease in anti‐dsDNA antibodies in those patients with the highest baseline levels, suggesting the presence of a more entrenched autoreactive plasma cell pool.…”

Section: Discussionmentioning

confidence: 77%

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Reddy

Martinez

Isenberg

et al. 2017

Arthritis Care & Research

View full text Add to dashboard Cite

ObjectiveB cell–depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with systemic lupus erythematosus (SLE). The aim of this observational study was to document long‐term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice.MethodsWe included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti‐dsDNA antibodies, over a median of 48 months most recent followup. Flow cytometry was used prospectively to assess B cell phenotypes in 17 of 57 patients.ResultsTwelve patients (21%) had persistent IgM hypogammaglobulinemia (<0.4 gm/liter), and 4 of 57 (5%) had low IgG (<7 gm/liter) at the most recent followup (range 12–144 months). This was not associated with serious adverse events or high anti–double‐stranded DNA (anti‐dsDNA) antibodies (>1,000 IU/ml; normal <50 IU/ml). Factors predictive of low serum IgM included baseline serum IgM ≤0.8 gm/liter (receiver operator curve analysis) and subsequent therapy with mycophenolate mofetil (MMF; odds ratio 6.8, compared with other immunosuppressants). In patients maintaining normal IgM levels (9 of 17), the frequency of circulating IgD+CD27+ B cells was significantly higher (P = 0.05). At 12 months after rituximab, 7 of 30 SLE patients with baseline anti‐dsDNA ≤1,000 IU/ml had lost seropositivity.ConclusionLower baseline serum IgM levels and sequential therapy with MMF were predictive of IgM hypogammaglobulinemia after rituximab in SLE, but this was not associated with higher levels of anti‐dsDNA antibodies or an increased risk of infections. This provides useful directions for clinicians regarding rituximab and sequential immunosuppressive treatment for patients with SLE.

show abstract

Section: Discussionmentioning

confidence: 77%

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Reddy

Martinez

Isenberg

et al. 2017

Arthritis Care & Research

View full text Add to dashboard Cite

show abstract

“…Thymic B cells present peptides derived from autoantigens captured by their B-cell receptors (BCRs) and potentially eliminate auto-reactive thymocytes [19]. This view is exemplified by the finding that MOG [35][36][37][38][39][40][41][42][43][44][45] peptide presenting thymic B cells have been shown to induce the deletion of MOG-specific T cells in the thymus of B MOG /2D2 mice [20]. These data demonstrate that thymic B cells contribute to the negative selection of self-reactive thymocytes.…”

Section: Discussionmentioning

confidence: 94%

Thymic B cells promote thymus-derived regulatory T cell development and proliferation

Yang

Wang

et al. 2015

Journal of Autoimmunity

View full text Add to dashboard Cite

“…8 Although total IgG may decline, stability of preexisting antigen-specific IgG following rituximabinduced B-cell depletion has been demonstrated. [29][30][31][32][33] However, several studies have shown that rituximab therapy effectively eliminates B cells from the peripheral blood but fails to effectively deplete all B cells within secondary lymphoid tissues. [34][35][36][37][38][39] Thus, whether PCs remaining in this setting are long-lived or dependent on replenishment by the residual B cells is unknown.…”

Section: Discussionmentioning

confidence: 99%

Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy

Bhoj

Arhontoulis

Wertheim

et al. 2016

Blood

212

160

View full text Add to dashboard Cite

• CD19-targeted T-cell immunotherapy reveals that a population of PCs lacking CD19 expression survives long-term, independent of B cells.• Preexisting humoral immunity to vaccine-related antigens can persist in patients despite marked B-cell aplasia after CTL019 immunotherapy.The mechanisms underlying the maintenance of long-lasting humoral immunity are not well understood. Studies in mice indicate that plasma cells (PCs) can survive up to a lifetime, even in the absence of regeneration by B cells, implying the presence of longlived PCs as a mechanism for long-lasting immunity. Evidence from humans treated with anti-CD20, which depletes circulating B cells, also suggests B-cell-independent longterm survival of some PCs. On the other hand, antibody responses may be sustained solely by short-lived PCs with repopulation from clonally related memory B cells. To explore PC longevity and humoral immunity in humans, we investigated the fate of PCs and their antibodies in adult and pediatric patients who received chimeric antigen receptor-based adoptive T-cell immunotherapy targeting CD19 to treat B-cell lineage malignancies (CTL019). Treatment with CTL019 is frequently associated with B-cell aplasia that can persist for years. Serum antibody titers to vaccine-related antigens were measured, and quantitative assessment of B cells and PCs in blood and bone marrow was performed at various time points before and after CTL019 therapy. While total serum immunoglobulin concentrations decline following CTL019-induced B-cell aplasia, several vaccine/pathogen-specific serum immunoglobulin G and A (IgG and IgA) titers remain relatively stable for at least 6 and 12 months posttreatment, respectively. Analysis of bone marrow biopsies after CTL019 revealed 8 patients with persistence of antibody-secreting PCs at least 25 months post-CTL019 infusion despite absence of CD19 1 CD20 1 B cells. These results provide strong evidence for the existence of memory B-cell-independent, long-lived PCs in humans that contribute to long-lasting humoral immunity. (Blood. 2016;128(3):360-370)

show abstract

The effect of B-cell depletion therapy on serological evidence of B-cell and plasmablast activation in patients with rheumatoid arthritis over multiple cycles of rituximab treatment

Cited by 74 publications

References 49 publications

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Thymic B cells promote thymus-derived regulatory T cell development and proliferation

Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy

Contact Info

Product

Resources

About