Dataset Information

A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients.

ABSTRACT:

Introduction

Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited.

Methods

We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq).

Results

After adjusting for multiple testing, plasma cells and regulatory B cells (B_REG) were significantly higher (P < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 0.042) and were associated with disease activity. Ex vivo-expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN patients. Tumor necrosis factor-α (TNF-α) was the only significantly increased cytokine in MN patients (P < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire.

Conclusion

This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity.

SUBMITTER: Cantarelli C

PROVIDER: S-EPMC7569696 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients.

Cantarelli Chiara C Jarque Marta M Angeletti Andrea A Manrique Joaquin J Hartzell Susan S O'Donnell Timothy T Merritt Elliot E Laserson Uri U Perin Laura L Donadei Chiara C Anderson Lisa L Fischman Clara C Chan Emilie E Draibe Juliana J Fulladosa Xavier X Torras Joan J Riella Leonardo V LV La Manna Gaetano G Fiaccadori Enrico E Maggiore Umberto U Bestard Oriol O Cravedi Paolo P

Kidney international reports 20200801 10

<h4>Introduction</h4>Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited.<h4>Methods</h4>We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytoki ...[more]

PMID: 33102969

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Project description:BackgroundThe value of anti-phospholipase A2 receptor antibody (anti-PLA2R ab) monitoring at 3 months after diagnosis in membranous nephropathy (MN) remains uncertain.MethodsWe retrospectively examined the outcome on 1 August 2020 of 59 adult patients (age 54 (44, 68) years, 69% male, SCr 1.0 (0.9, 1.3) mg/dL) diagnosed with MN (kidney biopsy, positive serum anti-PLA2R ab). The outcomes were: kidney survival; partial and/or complete remission.ResultsMost of the studied patients (97%) received immunosuppression, cyclophosphamide regimens were the most frequent (87%), followed by cyclosporine (10%). The median time to remission was 12.0 months and the cumulative remission rates were 34% at 6, 54% at 12, and 73% at 24 months. Forty (69%) patients had negative anti-PLA2R ab at 3 months, they had similar age, serum creatinine, albumin, proteinuria, and treatment with the group with positive ab at 3 months. In the Cox proportional hazard model, three months anti-PLA2R ab negativization (HR 0.4 (95%CI 0.1, 0.9)) was an independent predictor for remission, while baseline hypoalbuminemia (HR 3.0 (95%CI 1.5, 5.7)) was associated with absence of remission. Six (10%) patients died, mostly due to cardiovascular disease and infections. A total of five (9%) patients started dialysis. Mean kidney survival time was 50.3 months and there was no survival difference in relation to baseline anti-PLA2R ab titer (p .09) or 3 months negativization (p .8).ConclusionsThree months anti-PLA2R ab negativization seems to be a late predictor of remission, and lower serum albumin at diagnosis is an early marker for remission absence. Abbreviations: anti-P LA2R ab, anti-phospholipase A2 receptor antibody; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; MN, membranous nephropathy; NELL-1, neural epidermal growth factor-like 1 protein; RAAS: renin-angiotensin-aldosterone system; RBC: red blood cells; RRT, renal replacement therapy; T HSD7A, thrombospondin type-1 domain containing 7A.

Dataset Information

A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients.

Introduction

Methods

Results

Conclusion

Publications

A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients.

Similar Datasets

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