NELL1 is a target antigen in malignancy-associated membranous nephropathy.
NELL1 is a target antigen in malignancy-associated membranous nephropathy.
复制标题
NELL1是恶性肿瘤相关膜性肾病的靶抗原。
DOI：
10.1016/j.kint.2020.07.039
复制
发表时间：
2021-04
影响因子：
19.6
通讯作者：
Larsen CP
中科院分区：
文献类型：
--
作者：
Caza TN;Hassen SI;Dvanajscak Z;Kuperman M;Edmondson R;Herzog C;Storey A;Arthur J;Cossey LN;Sharma SG;Kenan DJ;Larsen CP
与普通人群相比，膜性肾病患者发生恶性肿瘤的风险增加，但与恶性肿瘤相关的膜性肾病的靶抗原尚不清楚。为了探索这一点，我们利用质谱学在恶性肿瘤相关膜性肾病中发现抗原，使用蛋白G珠免疫球蛋白捕获检测从冰冻肾活检组织中洗脱出来的免疫复合物。对未知类型和已知类型的膜性肾病患者进行抗原发现。质谱仪分析显示，膜性肾病的活检组织中存在神经表皮生长因子样1(NELL1)免疫复合体。随后通过免疫荧光鉴定了其他NELL1阳性病例。在连续的序列中，PLA2R和THSD7A阴性的病例中有3.8%为NELL1阳性。NELL1阳性病例中，节段性至不完全的Ig G毛细管环染色(93.4%)和显性或共显性Ig G1亚类染色(95.5%)。NELL1阳性膜性肾病患者的平均年龄为66.8岁，男性略占优势(58.2%)，33%合并恶性肿瘤。与PLA2R和THSD7A阳性的膜性肾病相比，NELL1相关组中恶性肿瘤的比例更高。因此，NELL1相关的膜性肾病具有独特的组织病理学特征，其特征是毛细血管环染色不完全，以IgG1为主，与其他已知类型的膜性肾病相比，它更常与恶性相关。结论：NELL1是恶性肿瘤相关膜性肾病的靶抗原。神经表皮生长因子样1(NELL1)是新近发现的膜性肾病的一种抗原，在恶性肿瘤相关的膜性肾病患者体内富含NELL1，血清中可检测到抗NELL1抗体。
Patients with membranous nephropathy have an increased risk of malignancy compared to the general population, but the target antigen for malignancy-associated membranous nephropathy is unknown. To explore this, we utilized mass spectrometry for antigen discovery in malignancy-associated membranous nephropathy examining immune complexes eluted from frozen kidney biopsy tissue using protein G bead immunoglobulin capture. Antigen discovery was performed comparing cases of membranous nephropathy of unknown and known type. Mass spectrophotometric analysis revealed that nerve epidermal growth factor-like 1 (NELL1) immune complexes were uniquely present within the biopsy tissue in membranous nephropathy. Additional NELL1-positive cases were subsequently identified by immunofluorescence. In a consecutive series, 3.8% of PLA2R- and THSD7A-negative cases were NELL1-positive. These NELL1-positive cases had segmental to incomplete IgG capillary loop staining (93.4%) and dominant or co-dominant IgG1-subclass staining (95.5%). The mean age of patients with NELL1-positive membranous nephropathy was 66.8 years, with a slight male predominance (58.2%) and 33% had concurrent malignancy. Compared with PLA2R- and THSD7A-positive cases of membranous nephropathy, there was a greater proportion of cases with malignancies in the NELL1-associated group. Thus, NELL1-associated membranous nephropathy has a unique histopathology characterized by incomplete capillary loop staining, IgG1-predominance, and is more often associated with malignancy than other known types of membranous nephropathy. CONCLUSION: NELL1 is a target antigen in malignancy-associated membranous nephropathy. Nerve epidermal growth factor-like 1 (NELL1), a recently identified antigen in membranous nephropathy, is enriched in patients with malignancy-associated membranous nephropathy, and anti-NELL1 antibodies can be detected within serum.
登录
查看更多内容
影响因子：
19.6
作者：
Birkeland, SA;Storm, HH
通讯作者：
Storm, HH
影响因子：
4.6
作者：
Lönnbro-Widgren J;Ebefors K;Mölne J;Nyström J;Haraldsson B
通讯作者：
Haraldsson B
影响因子：
4.6
作者：
Walker, Patrick D.
通讯作者：
Walker, Patrick D.
影响因子：
3.7
作者：
Franke A;Hampe J;Rosenstiel P;Becker C;Wagner F;Häsler R;Little RD;Huse K;Ruether A;Balschun T;Wittig M;Elsharawy A;Mayr G;Albrecht M;Prescott NJ;Onnie CM;Fournier H;Keith T;Radelof U;Platzer M;Mathew CG;Stoll M;Krawczak M;Nürnberg P;Schreiber S
通讯作者：
Schreiber S
影响因子：
3.4
作者：
Pani A;Porta C;Cosmai L;Melis P;Floris M;Piras D;Gallieni M;Rosner M;Ponticelli C
通讯作者：
Ponticelli C