The Many Faces of NELL1 MN

Abstract

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.

Neural epidermal growth factor-like 1 protein (NELL1)-associated membranous nephropathy with heterogeneous underlying diseases: A case report

“…This nding is consistent with the data from the Human Protein Atlas 17 and supports the previously reported possibility of breast cancer as a source of NELL1 antigen. 6 Our case depicts the di culty in interpreting NELL1-MN, reinforcing the ndings reported in the recent review by Sethi et al 5 NELL1-MN is associated with almost all causes of secondary MN. Therefore, we cannot conclude which underlying diseases have affected MN development in our case, even after establishing the diagnosis of NELL1-MN.…”

“…Several small studies suggested that MN might be induced by chronic HCV infection. 14 Additionally, Sethi et al 5 recently reported that NELL1-MN was detected in 25% of hepatitis B-associated MN cases and has also been detected in a patient with active hepatitis C. Thus, active HCV infection may have affected the development of NELL1-MN in our case.…”

“…Subsequently, NELL1-MN has been found in conjunction with malignant diseases, pre-exposure to certain drugs, infections, autoimmune diseases, hematopoietic stem cell transplant, de novo MN in a kidney transplant, and sarcoidosis. [5][6][7][8][9][10] Therefore, NELL1 has been recognized as a target antigen of secondary MN with heterogeneous underlying disease.…”

“…[2][3][4] Neural epidermal growth factor-like 1 protein (NELL1) is a recently discovered target antigen of MN, which accounts for 5-10% of cases. 5 An initial study reported that NELL1-positive MN (NELL1-MN) was the primary disease without underlying contributing illnesses. Subsequently, NELL1-MN has been found in conjunction with malignant diseases, pre-exposure to certain drugs, infections, autoimmune diseases, hematopoietic stem cell transplant, de novo MN in a kidney transplant, and sarcoidosis.…”

Characteristics and Outcomes of NELL1 Membranous Nephropathy in Lipoic Acid Users and Nonusers

“… 1 , 2 , 3 In 2019, 2 groups identified the NELL1 podocyte antigen in a subset of MN with distinct histologic and immunologic features, namely segmental or incomplete glomerular capillary loop involvement with predominant IgG1 staining. 4 , 5 NELL1 MN has also been identified in association with thiol-containing medications, namely lipoic acid, 6 , 7 bucillamine, 8 and tiopronin 9 ; traditional indigenous medications, including those with high mercury content 10 ; and with underlying conditions, including malignancy, 5 infections (including HIV 11 ), sarcoidosis, 12 hematopoietic stem cell transplant and graft-versus-host disease, 13 and rheumatoid arthritis. 8 …”