Posttransplant nephrotic syndrome resulting from NELL1-positive membranous nephropathy

Münch, Johannes; Krüger, Bastian M; Weimann, A.; Wiech, Thorsten; Reinhard, Linda; Hoxha, Elion; Pfister, Frederick; Halbritter, Jan

doi:10.1111/ajt.16610

Cited by 17 publications

(13 citation statements)

References 20 publications

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“…NELL1 MN associated with a transplant: NELL1 MN has been reported in transplants, both as a de novo MN in kidney transplant and as de novo MN following hematopoietic stem cell transplantation (HSCT) [ 21 , 22 ]. We have also detected NELL1 in one patient following HSCT for acute myelogenous leukemia (Fig.…”

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confidence: 99%

The Many Faces of NELL1 MN

Sethi

2022

Clinical Kidney Journal

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Neural tissue encoding protein with EGF-like repeats (NELL1) is a recently discovered target antigen in membranous nephropathy (MN). The initial study showed that most cases of NELL1-MN had no underlying disease associations, i.e. most cases of NELL1-MN were classified as primary MN. Subsequently, NELL1-MN has been found in the setting of various diseases. These include NELL1-MN associated with malignancy, drugs, infections, autoimmune disease, hematopoietic stem cell transplant, de novo MN in a kidney transplant and sarcoidosis. Thus, there is marked heterogeneity in the diseases associated with NELL1-MN. Evaluation of an underlying disease associated with MN will likely need to be more exhaustive in NELL1-MN.

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confidence: 99%

The Many Faces of NELL1 MN

Sethi

2022

Clinical Kidney Journal

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“…Approximately 50% of HIV-associated MN cases have tissue reactivity for PLA2R antigen [1,3], which is not always accompanied by detectable serum anti-PLA2R anti- bodies [3]. NELL1-positive MN has also been associated with malignancy [4], alpha-lipoic acid use [5][6][7], graft versus host disease after hematopoietic stem cell transplantation [8], and apparently primary MN [9,10]. Dual PLA2R and NELL1+ MN have been identified in 1 patient with detectable serum anti-PLA2R but not anti-NELL1 antibodies [10], and in one case based on mass spectrometry [11] but is considered rare.…”

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confidence: 99%

NELL1-Positive HIV-Associated Lupus-Like Membranous Nephropathy with Spontaneous Remission

Dinesh¹,

Charu

Troxell

et al. 2022

Glomerular Dis

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Introduction: Kidney biopsy findings in patients with human immunodeficiency virus (HIV) are diverse, and optimal therapy for the various immune complex diseases in the setting of HIV is unknown. Case Presentation: A man with well-controlled HIV developed nephrotic range proteinuria, and kidney biopsy revealed lupus-like glomerulonephritis with a predominantly membranous pattern of injury. He opted for conservative therapy and experienced spontaneous and sustained remission. Subsequent testing revealed neural epidermal growth factor-like 1 (NELL1)-positive glomerular immune deposits. NELL1-positive glomerular immune deposits were identified in a total of 2 of 5 tested HIV-associated membranous nephropathy (MN), which were morphologically dissimilar and one of which weakly co-expressed phospholipase A2 receptor (PLA2R). Discussion: This case suggests potentially different outcomes in patients with immune complex diseases in the setting of HIV based on disease etiology and histopathology. HIV-associated MN is occasionally NELL1-positive.

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“…The most well-known association is with malignancy, and up to 33% of NELL1-associated MN cases are thought to be related to malignancy 18 . Other known background conditions for NELL1-associated MN include associations with the intake of alpha lipoic acid 19 , intake of traditional indigenous medicine 20 , hematopoietic stem cell transplantation 21 , and post-kidney transplantation 22 . In our MN cohort, 2 of the 16 patients (12.5%) with NELL1-associated MN had colon cancer, supporting the previously reported association with malignancy.…”

Section: Discussionmentioning

confidence: 99%

Bucillamine use for rheumatoid arthritis and type 2 diabetes mellitus are associated with neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy

Tsuji

Iwasaki

Makita

et al. 2022

Preprint

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Membranous nephropathy (MN) is a disease characterized by deposition of immune complexes on the glomerular basement membrane. More than 10 specific antigens for MN including M-type phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A), exostosin 1/exostosin 2 (EXT1/EXT2) and neural epidermal growth factor-like 1 (NELL1) have so far been identified. Since the clinicopathologic characteristics of each type of MN in Japanese are not well understood, we first examined 107 cases of MN by immunohistochemistry for four antigens (PLA2R, THSD7A, EXT1, and NELL1) (MN-cohort). Of those 107 cases, 40% were PLA2R-positive, 13% were NELL1-positive, 11% were THSD7A-positive, 5% were EXT1-positive, 2% were PLA2R and NELL1-double-positive, and 29% were quadruple-negative. In one case of PLA2R and NELL1-double-positive, the first biopsy showed PLA2R-positive and the second biopsy showed PLA2R and NELL1-double-positive. Of the 16 cases of NELL1-positive, 12.5% had colon cancer, 18.8% had rheumatic diseases treated with bucillamine, and 63% had type 2 diabetes mellitus (T2DM). Next, 34 patients diagnosed with MN who had rheumatoid arthritis (RA) were examined (RA-MN cohort). Of those 34 patients, 79% were NELL1-positive, 6% were PLA2R-positive, and 15% were quadruple-negative. In the RA-MN cohort, 56% had a history of bucillamine use. In conclusion, NELL1-associated MN is a common MN in patients with RA using bucillamine and may also be associated with T2DM.

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Posttransplant nephrotic syndrome resulting from NELL1-positive membranous nephropathy

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 17 publications

References 20 publications

The Many Faces of NELL1 MN

The Many Faces of NELL1 MN

NELL1-Positive HIV-Associated Lupus-Like Membranous Nephropathy with Spontaneous Remission

Bucillamine use for rheumatoid arthritis and type 2 diabetes mellitus are associated with neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy

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