TY - JOUR
T1 - Heterogeneity of Target Antigens in Sarcoidosis-Associated Membranous Nephropathy
AU - Zubidat, Dalia
AU - Madden, Benjamin
AU - Kudose, Satoru
AU - Nasr, Samih H.
AU - Nardelli, Luca
AU - Fervenza, Fernando C.
AU - Sethi, Sanjeev
N1 - Funding Information:
This work was supported in part by funding to SS from the Department of Laboratory Medicine and Pathology at the Mayo Clinic (INNOV award). We acknowledge the assistance of the Mayo Clinic Proteomics Core, a shared resource of the Mayo Clinic Cancer Center (NCI P30 CA15083). We would like to thank LouAnn Gross and Vivian Negron in the Pathology Research Core for their help with histology and immunostaining.
Funding Information:
This work was supported in part by funding to SS from the Department of Laboratory Medicine and Pathology at the Mayo Clinic (INNOV award). We acknowledge the assistance of the Mayo Clinic Proteomics Core, a shared resource of the Mayo Clinic Cancer Center (NCI P30 CA15083). We would like to thank LouAnn Gross and Vivian Negron in the Pathology Research Core for their help with histology and immunostaining. SS and FCF designed the study. SS wrote the manuscript, interpreted the kidney biopsy, clinical, and IHC data. DZ and LN helped write the first draft and collect the clinical data. SN helped in collection of cases and in critical evaluation of the kidney biopsies. SK provided cases and clinical data from Columbia University. BM performed mass spectrometry studies. The manuscript was drafted and written by SS, with input as appropriate from all investigators.
Publisher Copyright:
© 2023 International Society of Nephrology
PY - 2023
Y1 - 2023
N2 - Introduction: Membranous nephropathy (MN) is the most common glomerular disease associated with sarcoidosis. The target antigen M-type phospholipase A2 receptor 1 (PLA2R) has been identified in a subset of sarcoidosis-associated MN. The target antigen is not known in the remaining sarcoidosis-associated MN. Methods: Data of patients with history of sarcoidosis and biopsy-proven MN were retrieved and analyzed. Mass spectrometry (MS/MS) was performed on all kidney biopsies of sarcoidosis-associated MN to detect the target antigens. Immunohistochemistry (IHC) studies were performed to confirm and localize the target antigens along the glomerular basement membrane (GBM). Results: Eighteen patients with history of sarcoidosis and biopsy-proven MN were identified, of whom 3 were known to be PLA2R-negative, and in the remaining patients the target antigen was unknown. Thirteen (72%) patients were males; the median age at MN diagnosis was 54.5 years. The median proteinuria at presentation was proteinuria 9.8 g/24 h. Eight patients (44.4%) had concurrent sarcoidosis. Using MS/MS, we detected PLA2R and neural epidermal growth factor-like-1 protein (NELL1) in 7 (46.6%) and 4 (22.2%) patients, respectively. In addition, 1 case each (5.5%) was positive for thrombospondin type 1 domain-containing 7A (THSD7A), protocadherin-7 (PCDH7), and putative antigen Serpin B12. No known target antigen was detected in the remaining 4 patients (22.2%). Conclusion: Patients with sarcoidosis and MN exhibit heterogeneous target antigens. We identified, along with PLA2R, the presence of previously unreported antigens, including NELL1, PCDH7, and THSD7A. The incidence of the target antigens in sarcoidosis appears to mirror the overall incidence of target antigens in MN. MN in sarcoidosis may be the result of a heightened immune response and is not associated with a single target antigen.
AB - Introduction: Membranous nephropathy (MN) is the most common glomerular disease associated with sarcoidosis. The target antigen M-type phospholipase A2 receptor 1 (PLA2R) has been identified in a subset of sarcoidosis-associated MN. The target antigen is not known in the remaining sarcoidosis-associated MN. Methods: Data of patients with history of sarcoidosis and biopsy-proven MN were retrieved and analyzed. Mass spectrometry (MS/MS) was performed on all kidney biopsies of sarcoidosis-associated MN to detect the target antigens. Immunohistochemistry (IHC) studies were performed to confirm and localize the target antigens along the glomerular basement membrane (GBM). Results: Eighteen patients with history of sarcoidosis and biopsy-proven MN were identified, of whom 3 were known to be PLA2R-negative, and in the remaining patients the target antigen was unknown. Thirteen (72%) patients were males; the median age at MN diagnosis was 54.5 years. The median proteinuria at presentation was proteinuria 9.8 g/24 h. Eight patients (44.4%) had concurrent sarcoidosis. Using MS/MS, we detected PLA2R and neural epidermal growth factor-like-1 protein (NELL1) in 7 (46.6%) and 4 (22.2%) patients, respectively. In addition, 1 case each (5.5%) was positive for thrombospondin type 1 domain-containing 7A (THSD7A), protocadherin-7 (PCDH7), and putative antigen Serpin B12. No known target antigen was detected in the remaining 4 patients (22.2%). Conclusion: Patients with sarcoidosis and MN exhibit heterogeneous target antigens. We identified, along with PLA2R, the presence of previously unreported antigens, including NELL1, PCDH7, and THSD7A. The incidence of the target antigens in sarcoidosis appears to mirror the overall incidence of target antigens in MN. MN in sarcoidosis may be the result of a heightened immune response and is not associated with a single target antigen.
KW - NELL1
KW - PLA2R
KW - mass spectrometry
KW - membranous nephropathy
KW - sarcoidosis
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U2 - 10.1016/j.ekir.2023.03.019
DO - 10.1016/j.ekir.2023.03.019
M3 - Article
AN - SCOPUS:85153291371
SN - 2468-0249
JO - Kidney International Reports
JF - Kidney International Reports
ER -