Dataset Information

A Diverse Spectrum of Immune Complex- and Complement-Mediated Kidney Diseases Is Associated With Mantle Cell Lymphoma.

ABSTRACT:

Introduction

There are limited reports on kidney biopsy findings in patients with mantle cell lymphoma (MCL).

Methods

We initiated a multi-institutional, retrospective review of kidney biopsy findings in patients with active and treated MCL.

Results

A total of 30 patients with MCL and kidney biopsies were identified, with a median age of 67 (range 48-87) years, 73% of whom were men. A total of 20 patients had active MCL at the time of biopsy, of whom 14 (70%) presented with acute kidney injury (AKI), proteinuria and/or hematuria, and biopsy findings potentially attributable to lymphoma. Of the 14, 11 had immune complex (IC) or complement-mediated (C3) disease including proliferative glomerulonephritis (GN) with monotypic Ig deposits (PGNMID [2]), C3GN, (2), secondary membranous nephropathy (MN [3]), tubular basement membrane (TBM) deposits (2), and modest lupus-like GN (2). Lymphomatous infiltration was present in 8 of the 20 patients, 5 with coincident IC or C3 lesions. A total of 6 patients with available follow-up were treated for MCL, all with clinical remission of GN (2 PGNMID, 2 C3GN, and 2 MN).

Conclusion

MCL is associated with diverse monoclonal and polyclonal glomerular and extra-glomerular IC and C3 disease. For patients with active MCL and kidney dysfunction requiring biopsy, 70% had findings due or potentially due to lymphoma, including 55% with IC or C3 disease and 40% had lymphomatous kidney infiltration. IC and C3GN in the setting of active MCL was responsive to lymphoma-directed therapy.

SUBMITTER: Andeen NK

PROVIDER: S-EPMC8897291 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

A Diverse Spectrum of Immune Complex- and Complement-Mediated Kidney Diseases Is Associated With Mantle Cell Lymphoma.

Andeen Nicole K NK Abdulameer Shahad S Charu Vivek V Zuckerman Jonathan E JE Troxell Megan M Kambham Neeraja N Alpers Charles E CE Najafian Behzad B Nicosia Roberto F RF Smith Kelly D KD Kung Vanderlene L VL Avasare Rupali S RS Vallurupalli Anusha A Jefferson J Ashley JA Hecox Douglas D Swetnam Leah L Yamashita Michifumi M Lin Mercury M Bissonnette Mei Lin ML Akilesh Shreeram S Hou Jean J

Kidney international reports 20211227 3

<h4>Introduction</h4>There are limited reports on kidney biopsy findings in patients with mantle cell lymphoma (MCL).<h4>Methods</h4>We initiated a multi-institutional, retrospective review of kidney biopsy findings in patients with active and treated MCL.<h4>Results</h4>A total of 30 patients with MCL and kidney biopsies were identified, with a median age of 67 (range 48-87) years, 73% of whom were men. A total of 20 patients had active MCL at the time of biopsy, of whom 14 (70%) presented with ...[more]

PMID: 35257069

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Project description:C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) are two rare diseases caused by dysregulated activity of the alternative pathway of complement secondary to the presence of genetic and/or acquired factors. Complement factor I (FI) is a serine protease that downregulates complement activity in the fluid phase and/or on cell surfaces in conjunction with one of its cofactors, factor H (FH), complement receptor 1 (CR1/CD35), C4 binding protein (C4BP) or membrane cofactor protein (MCP/CD46). Because altered FI activity is causally related to the pathogenesis of C3G and aHUS, we sought to test functional activity of select CFI missense variants in these two patient cohorts. We identified 65 patients (16, C3G; 48, aHUS; 1 with both) with at least one rare variant in CFI (defined as a MAF < 0.1%). Eight C3G and eleven aHUS patients also carried rare variants in either another complement gene, ADAMTS13 or THBD. We performed comprehensive complement analyses including biomarker profiling, pathway activity and autoantibody testing, and developed a novel FI functional assay, which we completed on 40 patients. Seventy-eight percent of rare CFI variants (31/40) were associated with FI protein levels below the 25th percentile; in 22 cases, FI levels were below the lower limit of normal (type 1 variants). Of the remaining nine variants, which associated with normal FI levels, two variants reduced FI activity (type 2 variants). No patients carried currently known autoantibodies (including FH autoantibodies and nephritic factors). We noted that while rare variants in CFI predispose to complement-mediated diseases, phenotypes are strongly contingent on the associated genetic background. As a general rule, in isolation, a rare CFI variant most frequently leads to aHUS, with the co-inheritance of a CD46 loss-of-function variant driving the onset of aHUS to the younger age group. In comparison, co-inheritance of a gain-of-function variant in C3 alters the phenotype to C3G. Defects in CFH (variants or fusion genes) are seen with both C3G and aHUS. This variability underscores the complexity and multifactorial nature of these two complement-mediated renal diseases.

Dataset Information

A Diverse Spectrum of Immune Complex- and Complement-Mediated Kidney Diseases Is Associated With Mantle Cell Lymphoma.

Introduction

Methods

Results

Conclusion

Publications

A Diverse Spectrum of Immune Complex- and Complement-Mediated Kidney Diseases Is Associated With Mantle Cell Lymphoma.

Similar Datasets

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