Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

Kurien, Abraham; Prema, K.S. Jansi; Walker, Patrick D.; Caza, Tiffany

doi:10.1016/j.kint.2022.09.001

Cited by 28 publications

(32 citation statements)

References 10 publications

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“…A recent study found NELL1 positivity in 87.9% of MN associated with traditional indigenous medicines, many of which contained high amounts of mercury. In comparison, only 9.1% of MN associated with indigenous medicines were positive for PLA2R [ 20 ].…”

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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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“…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%

“…The RA-MN cohort also included NELL1-associated MN cases that were not treated with BUC (cases 18,19,20,25,26). These cases suggest that drugs other than BUC may be responsible for NELL1-associated MN or that RA itself may induce NELL1-associated MN.…”

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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“…NELL1-associated MN is associated with malignancy in one-third of patients [25 ▪ ] and has also been identified in association with lipoic acid and traditional indigenous medicine use [26 ▪ ,27,28 ▪ ]. Indigenous medicines inciting NELL1-positive MN contained high levels of mercury, suggesting that NELL1 may be the target antigen in mercury-associated MN [28 ▪ ]. Glomerular deposits in NELL1-associated MN tend to be segmental [9 ▪ ,29].…”

Section: Antigen and Clinicopathologic Characteristics In Non-lupus M...mentioning

confidence: 99%

“…NELL1 is the second most prevalent MN autoantigen, comprising up to 16% of PLA2R-negative cases [6 ▪▪ ]. NELL1-associated MN is associated with malignancy in one-third of patients [25 ▪ ] and has also been identified in association with lipoic acid and traditional indigenous medicine use [26 ▪ ,27,28 ▪ ]. Indigenous medicines inciting NELL1-positive MN contained high levels of mercury, suggesting that NELL1 may be the target antigen in mercury-associated MN [28 ▪ ].…”

Section: Antigen and Clinicopathologic Characteristics In Non-lupus M...mentioning

confidence: 99%

The expanding spectrum and utility of antigens in membranous nephropathy

Miller

Caza

2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewMultiple antigenic targets were discovered in membranous nephropathy, representing distinct autoimmune diseases with a similar morphologic pattern of injury. An overview of recent developments, including antigen types, clinical associations, serologic monitoring, and advancements in understanding disease pathogenesis are provided. Recent findingsSeveral new antigenic targets have defined subtypes of membranous nephropathy, including Neural epidermal growth factor-like 1, protocadherin 7, HTRA1, FAT1, SEMA3B, NTNG1, NCAM1, exostosin 1/2, transforming growth factor beta receptor 3, CNTN1, proprotein convertase subtilisin/kexin type 6, and neuron-derived neurotrophic factor. Autoantigens in membranous nephropathy may demonstrate unique clinical associations, assisting the nephrologist to identify potential disease etiologies and triggers, such as autoimmune disease, cancer, medications, and infections.

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Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

Cited by 28 publications

References 10 publications

The Many Faces of NELL1 MN

The Many Faces of NELL1 MN

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

The expanding spectrum and utility of antigens in membranous nephropathy

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