B cell homeostasis is disturbed by immunosuppressive therapies in patients with ANCA-associated vasculitides

Thiel, Jens; Salzer, Ulrich; Hässler, Fabian; Effelsberg, Nora M.; Hentze, Carolin; Sic, Heiko; Bartsch, M; Miehle, Nikolaus; Peter, Hans; Warnatz, Klaus; Schlesier, Michael; Voll, Reinhard; Venhoff, Nils

doi:10.3109/08916934.2013.798652

Cited by 16 publications

(11 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prednisolone treatment in our study mainly affected the B-cell numbers whereas the distributions of B-cell subsets were in general unaffected. An effect of immunosuppressive treatment on the numbers of MZ-like B-cells, and other B-cell subsets, has also been described before ( 43 ). While treatment can explain differences between patients in remission and HC in our study, this is not the case for patients with active disease.…”

Section: Discussionmentioning

confidence: 57%

Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis

et al. 2018

View full text Add to dashboard Cite

In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and B1-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro, MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA. TNF and IL-10 were produced by both MZ-like and switched memory B-cells. Neither antibody nor TNF/IL-10 production by the B-cell subsets differed between patients and HC. Patients with autoimmune vasculitis, irrespective of disease activity, had lower percentage and absolute numbers of circulating MZ-like B-cells, and lower absolute numbers of B1-like B-cells. The percentage of B1-like B-cells was reduced during active disease. These findings remained significant when the analysis was confined to active treatment-naïve patients (disease onset).Our results suggest that human innate-like B-cells might have a physiological role in prevention of autoimmunity.

show abstract

Section: Discussionmentioning

confidence: 57%

Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Reduced transitional and mature B cells at baseline were probably caused by the concomitant immunosuppressive therapy [26][27][28] needed to maintain a persistent remission of NS. After complete depletion induced by RTX, total CD19 + B cells significantly increased at around 6 months as previously shown for RTX-treated patients with INS.…”

Section: Discussionmentioning

confidence: 99%

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

Colucci¹,

Carsetti²,

Cascioli

et al. 2015

JASN

172

165

View full text Add to dashboard Cite

The pathogenesis of nephrotic syndrome is unclear. However, the efficacy of rituximab, a B cell-depleting antibody, in nephrotic syndrome suggests a pathogenic role of B cells. In this retrospective study, we determined by flow cytometry levels of B and T cell subpopulations before and after rituximab infusion in 28 pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome. At baseline, patients had lower median percentages of transitional and mature B cells than age-matched healthy controls (P,0.001). Rituximab induced full depletion of B cells (,1% of lymphocytes). At 1 year, most patients exhibited complete total and mature B cell recovery, whereas memory B cell subsets remained significantly depleted. Total T cell concentration did not change with rituximab, whereas the CD4 + /CD8 + T cell ratio tended to increase. Fourteen patients relapsed within 24 months, with a median follow-up of 11.2 months (interquartile range, 8-17.7 months). We observed no difference at baseline between nonrelapsing and relapsing patients in several clinical parameters and cell subset concentrations. Reconstitution of all memory B cell subpopulations, number of immunosuppressive drugs, and dose of tacrolimus during the last 4 months of follow-up were predictive of relapse in univariate Cox regression analysis. However, only delayed reconstitution of switched memory B cells, independent of immunosuppressive treatment, was protective against relapse in multivariate (P,0.01) and receiver operator characteristic (P,0.01 for percentage of lymphocytes; P=0.02 for absolute count) analyses. Evaluation of switched memory B cell recovery after rituximab may be useful for predicting relapse in patients with nephrotic syndrome.

show abstract

“…Induction therapy with CYC was associated with a preferential depletion of naïve, double negative (CD27 − IgD − ) and pre-switched memory B cells, whereas treatment with MMF was not accompanied by a depletion of transitional or naïve B cells. Hence, especially naïve B cells seem to be more susceptible to CYC, a phenomenon also seen in patients with ANCA associated vasculitis receiving CYC for induction therapy [ 44 ] and in another SLE cohort [ 8 ]. Numbers of transitional B cells increased significantly after MMF was started, while they decreased after CYC was initiated, suggesting that MMF, in contrast to other immunosuppressants, spares transitional B cells.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus

Fassbinder¹,

Saunders²,

Mickholz³

et al. 2015

Arthritis Res Ther

View full text Add to dashboard Cite

IntroductionDisease activity and therapy show an impact on cellular and serological parameters in patients with systemic lupus erythematosus (SLE). This study was performed to compare the influence of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) therapy on these parameters in patients with flaring, organ-threatening disease.MethodsSLE patients currently receiving CYC (n = 20), MMF (n = 25) or no immunosuppressive drugs (n = 22) were compared using a cross-sectional design. Median disease activity and daily corticosteroid dose were similar in these treatment groups. Concurrent medication, organ manifestations, and disease activity were recorded, and cellular and serological parameters were determined by routine diagnostic tests or flow cytometric analysis. In addition follow-up data were obtained from different sets of patients (CYC n = 24; MMF n = 23).ResultsAlthough both drugs showed a significant effect on disease activity and circulating B cell subsets, only MMF reduced circulating plasmablasts and plasma cells as well as circulating free light chains within three months of induction therapy. Neither MMF nor CYC were able to reduce circulating memory B cells. MMF lowered IgA levels more markedly than CYC. We did not observe a significant difference in the reduction of IgG levels or anti-dsDNA antibodies comparing patients receiving MMF or CYC. In contrast to MMF, induction therapy with CYC was associated with a significant increase of circulating CD8+ effector T cells and plasmacytoid dendritic cells (PDCs) after three months.ConclusionsThe results indicate differences between MMF and CYC with regard to the mechanism of action. MMF, but not CYC, treatment leads to a fast and enduring reduction of surrogate markers of B cell activation, such as circulating plasmablasts, plasma cells and free light chains but a comparable rate of hypogammaglobulinemia.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0603-8) contains supplementary material, which is available to authorized users.

show abstract

B cell homeostasis is disturbed by immunosuppressive therapies in patients with ANCA-associated vasculitides

Cited by 16 publications

References 46 publications

Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis

Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus

Contact Info

Product

Resources

About