Decreased CD5+ B Cells in Active ANCA Vasculitis and Relapse after Rituximab

Bunch, Donna O.; G., McGregor, JulieAnne; Khandoobhai, Nirmal B.; Aybar, Lydia T.; Burkart, Madelyn; Hu, Yichun; Hogan, Susan L.; Poulton, Caroline J.; Berg, Elisabeth A.; Falk, Ronald J.; Nachman, Patrick H.

doi:10.2215/cjn.03950412

Cited by 84 publications

(70 citation statements)

References 39 publications

(41 reference statements)

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“…In humans, B-lymphocyte clusters have been observed in rapidly progressive GN kidneys, similar to those described in lupus nephritis (170). Aberrations in circulating B cells have been described in patients with active disease in AAV with increased BCR signaling, altered proportions of CD51 B cells, and decreased Breg numbers or function (105)(106)(107)171). Not surprisingly, therefore, rituximab in combination with corticosteroids is an effective (and Food and Drug Administrationapproved) therapy for inducing remission in patients with AAV, but its efficacy in treating patients with advanced renal disease has not been established yet (172).…”

Section: Role In Gnmentioning

confidence: 75%

“…Bregs have also been identified in humans, specifically in the CD24 high CD38 high transitional and CD24 high CD27 1 memory B-cell subsets, and their numbers correlate with better renal transplant outcomes (102)(103)(104). Altered numbers and/ or function of Bregs have been described in SLE and AAV, contributing to disease pathogenesis and/or relapse (102,(105)(106)(107). The presence of potent Bregs could explain why pan-depletion of B cells in humans using anti-CD20 (rituximab) has led to paradoxical or unsatisfactory clinical results in renal transplantation, as well as autoimmune renal disease (108,109).…”

Section: Bregsmentioning

confidence: 99%

See 1 more Smart Citation

B Cells, Antibodies, and More

Hoffman¹,

Lakkis

Chalasani

2016

Clinical Journal of the American Society of Nephrology

368

268

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B cells play a central role in the immunopathogenesis of glomerulonephritides and transplant rejection. B cells secrete antibodies that contribute to tissue injury via multiple mechanisms. In addition, B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and/or progression. B cell-targeted approaches for treating immune diseases of the kidney and other organs have gained significant momentum. However, much remains to be understood about B-cell biology in order to determine the timing, duration, and context of optimal therapeutic response to B cell-targeted approaches. In this review, we discuss the multifaceted roles of B cells as enhancers and regulators of immunity with relevance to kidney disease and transplantation.

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Section: Role In Gnmentioning

confidence: 75%

Section: Bregsmentioning

confidence: 99%

B Cells, Antibodies, and More

Hoffman¹,

Lakkis

Chalasani

2016

Clinical Journal of the American Society of Nephrology

368

268

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“…There must also be additional investigation into determining predictive markers for individuals who need fixed versus intermittent dosing. It seems that higher relative percentages of peripheral regulatory B cells at the time of B-cell repopulation after rituximab may be associated with more prolonged remission (20,21). This finding could imply an increased risk of relapse at the time of rituximab cessation.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

Pendergraft

Cortazar

Wenger³

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission.Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined.Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase-ANCA) treated from Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted.

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“…Bunch et al (43) have observed that the percentage of peripheral blood CD5-positive regulatory B cells is a useful indicator of disease activity, remission, and future relapse after rituximab therapy, and thus may help measure the effectiveness of induction therapy and guide maintenance therapy vigilance for relapse. To our knowledge, assays for CD5-positive B cells are not routinely available in clinical laboratories, although this test could be added to current flow cytometry lymphocyte phenotyping assays as a locally validated laboratory-developed test.…”

Section: Induction Of Remissionmentioning

confidence: 99%

ANCA Glomerulonephritis and Vasculitis

Jennette¹,

Nachman²

2017

CJASN

Self Cite

269

214

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ANCA vasculitis has an associated autoimmune response that produces ANCAs that induce distinct pathologic lesions. Pauci-immune necrotizing and crescentic GN is a frequent component of ANCA vasculitis. ANCA vasculitis is associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). A diagnosis of ANCA vasculitis should always specify the serotype as MPO-ANCA positive, PR3-ANCA positive, or ANCAnegative. To fully characterize a patient, the serotype also should be accompanied by the clinicopathologic variant if this can be determined: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener), eosinophilic granulomatosis with polyangiitis (Churg-Strauss), or renal-limited vasculitis. ANCA vasculitis is most prevalent in individuals >50 years old. There are racial/ethnic and geographic influences on the prevalence, serotype frequencies, and clinicopathologic phenotypes. There is clinical, in vitro, and animal model evidence that ANCAs cause disease by activating neutrophils to attack small vessels. Immunomodulatory and immunosuppressive therapies are used to induce remission, maintain remission, and treat relapses. Over recent years, there have been major advances in optimizing treatment by minimizing toxic therapy and utilizing more targeted therapy.

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Decreased CD5+ B Cells in Active ANCA Vasculitis and Relapse after Rituximab

Cited by 84 publications

References 39 publications

B Cells, Antibodies, and More

B Cells, Antibodies, and More

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

ANCA Glomerulonephritis and Vasculitis

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