Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis

被引:105
作者
Caza, Tiffany N. [1 ]
Hassen, Samar I. [1 ]
Kuperman, Michael [1 ]
Sharma, Shree G. [1 ]
Dvanajscak, Zeljko [1 ]
Arthur, John [2 ]
Edmondson, Rick [2 ]
Storey, Aaron [2 ]
Herzog, Christian [2 ]
Kenan, Daniel J. [1 ]
Larsen, Christopher P. [1 ]
机构
[1] Arkana Labs, 10810 Execut Ctr Dr,100, Little Rock, AR 72211 USA
[2] Univ Arkansas Med Sci, Little Rock, AR USA
基金
美国国家卫生研究院;
关键词
glomerular disease; immune complex; lupus nephritis; membranous nephropathy; serum testing; systemic lupus erythematosus; DOMAIN-CONTAINING; 7A; ERYTHEMATOSUS; ANTIBODIES; EXPRESSION; RECEPTOR; DISEASE;
D O I
10.1016/j.kint.2020.09.016
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. It has been shown in phospholipase A2 receptor positive membranous nephropathy that known antibodies can be detected within sera, determination of the target autoantigen can have diagnostic significance, inform prognosis, and enable non-invasive monitoring of disease activity. Here we utilized mass spectrometry for antigen discovery in laser captured microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue protein G immunoprecipitation studies to interrogate immune complexes from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in some cases of membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1 association was 6.6% of cases of membranous lupus nephritis and in 2.0% of primary membranous nephropathy cases. NCAM1 was found to colocalize with IgG within glomerular immune deposits by confocal microscopy. Additionally, serum from patients with NCAM1-associated membranous nephropathy showed reactivity to NCAM1 recombinant protein on Western blotting and by indirect immunofluorescence assay, demonstrating the presence of circulating antibodies. Thus, we propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.
引用
收藏
页码:171 / 181
页数:11
相关论文
共 27 条
[1]   Update on Lupus Nephritis [J].
Almaani, Salem ;
Meara, Alexa ;
Rovin, Brad H. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 12 (05) :825-835
[2]   M-Type Phospholipase A(sub 2) Receptor as Target Antigen in Idiopathic Membranous Nephropathy. [J].
Beck, Laurence H., Jr. ;
Bonegio, Ramon G. B. ;
Lambeau, Gerard ;
Beck, David M. ;
Powell, David W. ;
Cummins, Timothy D. ;
Klein, Jon B. ;
Salant, David J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (01) :11-21
[3]   Renal Manifestations of Common Variable Immunodeficiency [J].
Caza, Tiffany N. ;
Hassen, Samar I. ;
Larsen, Christopher P. .
KIDNEY360, 2020, 1 (06) :491-500
[4]   The ProteomeXchange consortium in 2020: enabling 'big data' approaches in proteomics [J].
Deutsch, Eric W. ;
Bandeira, Nuno ;
Sharma, Vagisha ;
Perez-Riverol, Yasset ;
Carver, Jeremy J. ;
Kundu, Deepti J. ;
Garcia-Seisdedos, David ;
Jarnuczak, Andrew F. ;
Hewapathirana, Suresh ;
Pullman, Benjamin S. ;
Wertz, Julie ;
Sun, Zhi ;
Kawano, Shin ;
Okuda, Shujiro ;
Watanabe, Yu ;
Hermjakob, Henning ;
MacLean, Brendan ;
MacCoss, Michael J. ;
Zhu, Yunping ;
Ishihama, Yasushi ;
Vizcaino, Juan A. .
NUCLEIC ACIDS RESEARCH, 2020, 48 (D1) :D1145-D1152
[5]  
Dvanajscak Z, KIDNEY INT, V99, P967
[6]  
Ehrenreich T, 1968, PATHOL ANNU, V3, P145
[7]   Thrombospondin Type-1 Domain-Containing 7A in Idiopathic Membranous Nephropathy [J].
Goedel, Markus ;
Grahammer, Florian ;
Huber, Tobias B. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (11) :1073-1073
[8]   Anti-Phospholipase A2 Receptor Antibodies Correlate with Clinical Status in Idiopathic Membranous Nephropathy [J].
Hofstra, Julia M. ;
Beck, Laurence H., Jr. ;
Beck, David M. ;
Wetzels, Jack F. ;
Salant, David J. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 6 (06) :1286-1291
[9]   An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy [J].
Hoxha, Elion ;
Beck, Laurence H., Jr. ;
Wiech, Thorsten ;
Tomas, Nicola M. ;
Probst, Christian ;
Mindorf, Swantje ;
Meyer-Schwesinger, Catherine ;
Zahner, Gunther ;
Stahl, Phillip R. ;
Schoepper, Ruth ;
Panzer, Ulf ;
Harendza, Sigrid ;
Helmchen, Udo ;
Salant, David J. ;
Stahl, Rolf A. K. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 28 (02) :520-531
[10]  
Huong DLT, 1999, MEDICINE, V78, P148