Correlation between B Lymphocyte Abnormality and Disease Activity in Patients with Idiopathic Membranous Nephropathy

Wang, B; K, Zuo; Wu, Yuzhang; Huang, Qipeng; Ws, Qin; Ch, Zeng; Ls, Li; Zh, Liu

doi:10.1177/147323001103900111

Cited by 24 publications

(25 citation statements)

References 28 publications

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“…Patients with a mutation in FOXP3, a transcription factor which programs the development and function of CD4 + CD25 + regulatory T-cells, occasionally develop MN 20,21 . Compared with healthy controls, the number of peripheral blood CD4 + CD25 + Foxp3 + regulatory T-cells was reduced in patients with PMN, while the amount of peripheral blood B-lymphocytes was higher, although no correlation was found with proteinuria 12,22 . At variance with these data, Fervenza et al, found that none of the Treg subsets showed quantitative differences, the only persistent change in lymphocyte subsets being a relative increase in natural killer cells 13 .…”

Section: Introductionmentioning

confidence: 69%

“…A panel of 27 cytokines and chemokines was assayed to investigate the Th1/Th2/Th17 12 and Italy 22 whereas a study from the Mayo Clinic found that none of the Treg subsets showed quantitative differences 13 . Roccatello et al 22 showed that in patients treated with rituximab, there was an increase in Treg at month 12, but there was no information on early time points before month 6.…”

Section: Cytokine Profile In Pmn Patients and Outcome With Niat-rituxmentioning

confidence: 99%

“…These data are consistent with previous reports in other autoimmune diseases like SLE and Sjogren's syndrome 28,29 . They indicate that the Bcell compartment undergoes alterations that are apparent in the distribution of the B-cell subsets present in the circulation, which suggests that B-cell tolerance checkpoints are impaired in these autoimmune diseases 29 .The lower rate of circulating memory B cells could be explained by over-expression of chemokines that guide them into tissues as suggested by immunochemistry studies showing B-cell infiltration in kidneys 12,[29][30][31] , and/or by an increased differentiation of self-reactive B cells into autoantibody producing plasmablasts under the control of T follicular helper (Tfh) cells 29,32 . Exploration of Tfh cells in PMN would be important in future studies.…”

Section: Cytokine Profile In Pmn Patients and Outcome With Niat-rituxmentioning

confidence: 99%

“…At variance with antibodies, circulating lymphocyte populations have been poorly investigated in PMN. Old studies have shown an increase of the CD4 + /CD8 + subset ratio in some patients with MN, with or without nephrotic syndrome [5][6][7][8][9][10][11][12] . In the subset of patients with MN and nephrotic syndrome, some patients had a marked increase in the CD4 + /CD8 + ratio due to a reduction in the CD8 cell subset compared to healthy subjects while others showed a ratio in the normal range 6 It was suggested that a high CD4 + /CD8 + ratio might predict clinical response to immunosuppressive treatment 9 although this was not confirmed by later studies in patients treated with rituximab 13 .…”

Section: Introductionmentioning

confidence: 99%

“…First, we wanted to take advantage of the progress achieved in the characterization of lymphocyte subpopulations in an attempt to solve out the discrepancies previously observed 12,13 . Second, our randomized controlled trial of rituximab plus supportive therapy versus supportive therapy alone made it possible to investigate whether dynamic changes in specific lymphocyte populations might predict response to rituximab in patients with severe PMN 23 .…”

Section: Introductionmentioning

confidence: 99%

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B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab

Rosenzwajg¹,

Languille²,

Dębiec³

et al. 2017

Kidney International

112

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Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56CD16 NK subset. There were a significantly decreased percentage of regulatory T cells, together with an increased plasma concentration of TNF-alpha, IL-5 and IL-2RA. We then investigated 16 patients at eight days and three and six months after treatment with rituximab added to supportive therapy compared to nine patients with supportive therapy alone. After rituximab, B-cell recovery was still incomplete at six months, with persistent alterations of B-cell subsets, a significant increase of both T-regulatory (Treg) cells and NK cells, and a significant decrease of both the CD56CD16 NK subset and TNF-alpha levels. The patients who clinically responded to rituximab had a significantly lower percentage of Tregs at baseline compared to non-responders and a significantly increased percentage at day eight. Tregs remained unchanged in non-responders and in patients treated with supportive therapy alone. Thus, evaluation of Tregs might be useful for predicting early response to rituximab.

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Section: Introductionmentioning

confidence: 69%

Section: Cytokine Profile In Pmn Patients and Outcome With Niat-rituxmentioning

confidence: 99%

Section: Cytokine Profile In Pmn Patients and Outcome With Niat-rituxmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab

Rosenzwajg¹,

Languille²,

Dębiec³

et al. 2017

Kidney International

112

View full text Add to dashboard Cite

show abstract

Regulatory T cells in renal disease

et al. 2018

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The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen‐specific Tregs in HLA‐mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype. Experimentally, Tregs can protect the kidney from injury in a variety of renal diseases. Mechanisms of Treg recruitment to the kidney include via the chemokine receptors CCR6 and CXCR3 and potentially, at least in innate injury TLR9. The effects of Tregs may be context dependent, with evidence for roles for immunoregulatory roles both for endogenous Tbet‐expressing Tregs and STAT‐3‐expressing Tregs in experimental glomerulonephritis. Most experimental work and some of the ongoing human trials in renal transplantation have focussed on unfractionated thymically derived Tregs (tTregs). However, induced Tregs (iTregs), type 1 regulatory T (Tr1) cells and in particular antigen‐specific Tregs also have therapeutic potential not only in renal transplantation, but also in other kidney diseases.

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Regulatory B Cells Are Reduced and Correlate With Disease Activity in Primary Membranous Nephropathy

Ramachandran

Kaundal

Girimaji

et al. 2020

Kidney International Reports

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Introduction: Primary membranous nephropathy (PMN) is an autoimmune disease. Both T-regulatory cells (TREGs) and B-regulatory cells (BREGs) are decreased in patients with autoimmune disease. We evaluated the TREG and BREG population in patients of PMN treated with cyclical cyclophosphamide and steroid therapy (cCYC/GC).Methods: Twenty-four patients with PMN resistant to a restrictive strategy and treated with cCYC/GC therapy and 10 healthy controls were enrolled. The proteinuria, serum creatinine, and serum albumin were tested at monthly intervals and blood samples were collected before starting cCYC/GC and at 6 and 8 (2 months wash out) months of therapy. The peripheral blood mononuclear cells (PBMCs) after staining with fluorochrome-conjugated antibodies were then subjected to flow cytometric analysis for detection of TREGs (CD3þCD4þCD25hiCD127loFoxP3þ) and BREGs (CD19þCD5þCD1dhiIL10þ). TREGs and BREGs are presented as the percentage of T and B cells, respectively. Cases with remission at month 18 were classified as responders, and those without any remission as nonresponders.Results: Patients with PMN had a lower percentage of TREGs (P ¼ 0.07) and BREGs compared with healthy controls (P ¼ 0.0007). As compared with baseline, there was a significant increase in both BREGs (P ¼ 0.001) and TREGs (P ¼ 0.02) with the treatment (8 months). Patients who responded to therapy by 18 months had an increase in TREG (P ¼ 0.05) and BREG (P ¼ 0.0001) at month 8 compared with baseline. Conclusion:As compared with healthy controls, patients with PMN displayed a lower percentage of BREGs. Both TREGs and BREGs significantly improved with disease-specific therapy. BREGs had an association with clinical activity.

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Correlation between B Lymphocyte Abnormality and Disease Activity in Patients with Idiopathic Membranous Nephropathy

Cited by 24 publications

References 28 publications

B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab

B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab

Regulatory T cells in renal disease

Regulatory B Cells Are Reduced and Correlate With Disease Activity in Primary Membranous Nephropathy

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