B cell repopulation kinetics after rituximab treatment in ANCA-associated vasculitides compared to rheumatoid arthritis, and connective tissue diseases: a longitudinal observational study on 120 patients

Thiel, Jens; Rizzi, Marta; Engesser, Marie; Dufner, Ann-Kathrin; Troilo, Arianna; Lorenzetti, Raquel; Voll, Reinhard; Venhoff, Nils

doi:10.1186/s13075-017-1306-0

Cited by 91 publications

(70 citation statements)

References 22 publications

(19 reference statements)

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“…Hypogammaglobulinaemia following B cell depletion therapy or targeting of B cell growth factors is common, occurring in 30-56% of patients with AAV after rituximab treatment (173,174), and in up 2% of patients with SLE in the first year of belimumab therapy with levels falling by a median of 13% after 4 years of treatment (175). Total dose exposure of rituximab therapy may not predict hypogammaglobulinaemia, as this effect is more likely to be related to the duration of B cell depletion (174).…”

Section: [H2] Kidney Transplantationmentioning

confidence: 99%

Effector and regulatory B cells in immune-mediated kidney disease

2018

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B cells have a central role in many autoimmune diseases, including in those with renal involvement, as well as in the immunological response to kidney transplantation. The majority of studies of B cells have focused on their pathological role as antibody producers. However, these cells have broad functions in immune responses beyond immunoglobulin secretion, including antigen presentation to T cells and cytokine production. Importantly, not all B cell subsets enhance immune responses. Regulatory B (Breg) cells attenuate inflammation and contribute to the maintenance of immune tolerance. Breg cells are numerically deficient and/or dysfunctional in several autoimmune diseases that can affect the kidney, including systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis, as well as in some groups of renal transplant recipients with alloimmune graft damage. B cell-targeting biologics have been trialled with promising results in diverse immune-mediated renal conditions. These therapies can affect both pro-inflammatory B cells and Breg cells potentially limiting their long-term efficacy. Future strategies might involve the modulation of inflammatory B cells in combination with the stimulation of regulatory subsets. Additionally, the monitoring of individual B cell subsets in patients may lead to the discovery of novel biomarkers that could help to predict disease relapse or progression.

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Section: [H2] Kidney Transplantationmentioning

confidence: 99%

Effector and regulatory B cells in immune-mediated kidney disease

2018

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“…As AAV frequently relapses, repeated RTX infusions are used as maintenance treatment. However, as RTX induces a long-lasting depletion of B-cells, it has been associated with an altered B-cell maturation capacity (31). Furthermore, prolonged B-cell depletion may lead to decreased antibody production, as assessed by two retrospective studies in which severe infections and hypogammaglobulinemia were frequent adverse events (26,27).…”

Section: Discussionmentioning

confidence: 99%

Lower cranial nerve palsy during radiotherapy for glottic cancer in a patient with Wegener's granulomatosis: An interesting case report

et al. 2018

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The aim of the present study was to report an unusual case of multiple lower cranial nerve palsies in a patient with Wegener's granulomatosis (WG) during radiotherapy for glottic cancer. WG is an autoimmune disease characterized by necrotizing granulomas mainly in the upper and lower respiratory tract or kidneys; however, the involvement of cranial nerves is not uncommon. Prior to the use of cyclophosphamide (CYC) the 1-year mortality rate was ~82%; the introduction of rituximab (RTX) has revolutionized the course of the WG, with remission rates comparable to those of CYC and superior effectiveness in relapsing patients. Hypogammaglobulinemia and B-cell depletion are the best known monitored side effects affecting survival due to secondary infections. Immunodepression and relapse with lower cranial nerve palsy have a negative impact on prognosis. We herein present the case of a heavily pre-treated GPA patient with secondary immunosuppression, who underwent radiotherapy for glottic cancer and developed multiple low cranial nerve palsies during treatment, which was interrupted at 60 Gy. The possible related causes and the association between previous immunosuppressive treatments and radiotherapy were also analyzed to elucidate the cause of this complication.

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“…To test the potential use of CD3-(CD56 or CD16)+ NK cell percentages and counts as disease activity biomarker in ANCA-associated vasculitis, we retrospectively analyzed existing lymphocyte subset data from two German vasculitis centers [24]. Lymphocyte subpopulations phenotyping…”

Section: Methodsmentioning

confidence: 99%

CD3-(CD56 or 16)+ natural killer cell distribution in blood from healthy adults and patients with ANCA-associated vasculitis

Merkt¹,

Salzer²,

Thiel³

et al. 2020

Preprint

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BackgroundCytotoxic Natural Killer (NK) cells are an important target of new drugs entering the clinics, including checkpoint inhibitors and cell-depleting therapeutic antibodies. Still, basic blood NK cell parameters are poorly defined in healthy adults and in chronic inflammatory diseases like ANCA-associated vasculitis (AAV) which may alter the distribution of lymphocytes. The aims of this study were 1) to establish reference values of NK cell counts and percentages in healthy adults; 2) to describe these parameters in AAV; and 3) to investigate whether NK cell counts and percentages may be used as activity biomarker in the care of AAV patients, as suggested by a preceding study.MethodsCD3-(CD56 or 16)+ NK cell counts and percentages were determined in 120 healthy adults. Lymphocyte subset data from two German vasculitis centers were retrospectively analyzed (in total 407 measurements, including 201/49/157 measurements from 64/16/39 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), respectively).ResultsCD3-(CD56 or 16)+ NK cell counts and percentages in healthy adults were highly variable, not Gaussian distributed and independent of age and sex. NK cell percentages ranged from 1.9 to 37.9% of lymphocytes, and were significantly more dispersed in AAV (0.3 to 57.6%). We further found that NK cell counts and percentages were different between AAV entities. However, during active disease, NK cell counts were consistently low in each AAV entity compared to healthy donors. NK cells were especially low in inactive EGPA. In 18% of EGPA patients we observed percentages of 1% or below which may be interpreted as temporary NK cell deficiency. Findings on differences between active and inactive GPA were discrepant between vasculitis centers.ConclusionsNK cell counts and percentages in blood are highly variable. This variability is further enhanced in systemic inflammatory diseases, and includes patients with temporary NK cell deficiency, in particular in EGPA. NK cell counts and percentages can presently not be recommended as biomarker in clinical care of AAV patients.

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B cell repopulation kinetics after rituximab treatment in ANCA-associated vasculitides compared to rheumatoid arthritis, and connective tissue diseases: a longitudinal observational study on 120 patients

Cited by 91 publications

References 22 publications

Effector and regulatory B cells in immune-mediated kidney disease

Effector and regulatory B cells in immune-mediated kidney disease

Lower cranial nerve palsy during radiotherapy for glottic cancer in a patient with Wegener's granulomatosis: An interesting case report

CD3-(CD56 or 16)+ natural killer cell distribution in blood from healthy adults and patients with ANCA-associated vasculitis

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