NELL1 is a target antigen in malignancy-associated membranous nephropathy

Area of Science:

• Nephrology
• Oncology
• Immunopathology

Background:

• Membranous nephropathy (MN) is linked to an elevated risk of malignancy.
• The specific antigens driving malignancy-associated MN remain largely unidentified.
• Existing research lacks clarity on the pathological characteristics of malignancy-associated MN.

Purpose of the Study:

• To identify novel antigens associated with malignancy-induced membranous nephropathy.
• To characterize the distinct histopathological features of NELL1-associated MN.
• To investigate the association between NELL1-positive MN and concurrent malignancies.

Main Methods:

• Mass spectrometry was employed to analyze immune complexes from kidney biopsy tissues.
• Protein G bead immunoglobulin capture technique was used for antigen discovery.
• Immunofluorescence staining confirmed the presence of NELL1 in additional cases.

Main Results:

• Nerve epidermal growth factor-like 1 (NELL1) immune complexes were uniquely identified in MN kidney biopsies.
• NELL1-positive MN cases exhibited segmental to incomplete IgG capillary loop staining and IgG1-subclass predominance.
• A significant proportion (33%) of NELL1-positive MN patients had concurrent malignancies, higher than PLA2R/THSD7A-positive MN.

Conclusions:

• NELL1 is a novel target antigen in a subset of membranous nephropathy, particularly associated with malignancy.
• NELL1-associated MN presents unique histopathological findings, including incomplete capillary loop staining and IgG1 predominance.
• This discovery aids in identifying patients with a higher risk of underlying cancer among MN cases negative for other known antigens.