scholarly journals Genetic determinants of the development and course of membranous nephropathy

2018 ◽  
Vol 90 (6) ◽  
pp. 105-111 ◽  
Author(s):  
E S Kamyshova ◽  
I N Bobkova ◽  
I A Gorelova ◽  
P A Kakhsurueva ◽  
E E Filatova
Keyword(s):  
Membranous Nephropathy ◽  
Genetic Factors ◽  
Genetic Determinants ◽  
Systemic Autoimmune Diseases ◽  
Phospholipase A2 Receptor ◽  
Common Causes ◽  
Human Leucocyte Antigen Class ◽  
Circulating Antibodies

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.

scholarly journals Clinicopathological features in membranous nephropathy with cancer: A retrospective single-center study and literature review

2019 ◽  
Vol 34 (4) ◽  
pp. 406-413
Author(s):  
Dan Zhang ◽  
Chong Zhang ◽  
Fan Bian ◽  
Wenzhu Zhang ◽  
Gengru Jiang ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinicopathological Characteristics ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Patients With Cancer ◽  
Phospholipase A2 Receptor ◽  
Single Center Study ◽  
Close Relationship ◽  
Circulating Antibodies

Background: Membranous nephropathy is the most common glomerular disease related to malignancy. However, it is difficult to distinguish between true malignancy-related membranous nephropathy and idiopathic membranous nephropathy coincident with cancer. It has been reported that phospholipase A2 receptor (PLA2R) is the first autoantigen involved in idiopathic membranous nephropathy and thrombospondin type-1 domain-containing 7A (THSD7A) may have a close relationship with malignancy-related membranous nephropathy. Therefore, the aim of this study was to compare the clinicopathological characteristics between membranous nephropathy patients with cancer and idiopathic membranous nephropathy patients without cancer to better detect malignancy-related membranous nephropathy, including glomerular PLA2R and THSD7A depositions and their circulating antibodies, together with glomerular IgG4 deposition. Methods: Twelve membranous nephropathy patients with cancer and 257 idiopathic membranous nephropathy patients without cancer were included in this study and had been followed up for more than 1 year. The glomerular expression of PLA2R, THSD7A, and IgG4 was analyzed by immunohistochemistry. Circulating anti-PLA2R and anti-THSD7A antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence testing, respectively. Results: Membranous nephropathy patients with cancer were significantly older and had higher serum creatinine and a lower estimated glomerular filtration rate than idiopathic membranous nephropathy patients ( P<0.05). The positive rates of glomerular PLA2R and IgG4 depositions and circulating anti-PLA2R antibodies in membranous nephropathy patients with cancer were significantly lower than those in idiopathic membranous nephropathy patients without cancer ( P<0.01). Conclusion: The absence of glomerular PLA2R deposition and negative circulating anti-PLA2R antibodies, along with negative glomerular IgG4 staining, may be useful clues to more accurately screen underlying malignancies in membranous nephropathy patients.

Genetic aspects of intervertebral disc degeneration

2015 ◽  
Vol 26 (5) ◽  
pp. 581-606 ◽  
Author(s):  
Sara Hanaei ◽  
Sina Abdollahzade ◽  
Alireza Khoshnevisan ◽  
Christopher K. Kepler ◽  
Nima Rezaei
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Genetic Factors ◽  
Wide Spectrum ◽  
Nucleotide Polymorphisms ◽  
Disc Disease ◽  
Multifactorial Diseases ◽  
Common Causes

AbstractIntervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.

Neural Epidermal Growth Factor–Like 1 Protein–Positive Membranous Nephropathy in Chinese Patients

2021 ◽  
pp. CJN.11860720
Author(s):  
Guoqin Wang ◽  
Lijun Sun ◽  
Hongrui Dong ◽  
Yanyan Wang ◽  
Xiaoyi Xu ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinical Characteristics ◽  
Chinese Patients ◽  
Double Positive ◽  
Immunohistochemistry Staining ◽  
Phospholipase A2 Receptor ◽  
Pathologic Features ◽  
Glomerular Deposits ◽  
Epidermal Growth

Background and objectivesThe neural EGF-like 1 (NELL-1) protein is a novel antigen in primary membranous nephropathy. The prevalence and clinical characteristics of NELL-1–positive membranous nephropathy in Chinese individuals with primary membranous nephropathy are unclear.Design, setting, participants, & measurementsA total of 832 consecutive patients with biopsy-proven primary membranous nephropathy were enrolled. The glomerular expression of phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) was screened. Glomerular immunohistochemistry staining for NELL-1 was performed in 43 patients with PLA2R- and THSD7A-negative membranous nephropathy, 31 patients with PLA2R-positive membranous nephropathy, and two patients with PLA2R and THSD7A double positivity. The NELL-1 antibody was also detected in the sera of patients with NELL-1–positive membranous nephropathy by western blot. Clinical and pathologic features were comparable between patients with isolated NELL-1–positive, isolated PLA2R/THSD7A-positive, and triple antigen–negative membranous nephropathy.ResultsAmong the 832 patients with primary membranous nephropathy, 11 of 54 (20%) patients with PLA2R-negative membranous nephropathy had THSD7A-positive membranous nephropathy. NELL-1–positive membranous nephropathy accounted for 35% (15 of 43) of all patients with PLA2R- and THSD7A-negative membranous nephropathy. One patient was double positive for NELL-1 and PLA2R in glomerular deposits and positive for only the PLA2R antibody in the serum. Most patients with NELL-1–positive membranous nephropathy were women. No tumors were found. There were significant differences in the prevalence of IgG subtypes between patients with different antigen positivity. Among patients with isolated NELL-1–positive membranous nephropathy, although 80% (12 of 15) were IgG4 staining positive, the proportion of IgG4 dominance was only 67% (ten of 15).ConclusionsAbout one third of patients who were PLA2R and THSD7A negative were NELL-1 positive in Chinese patients with primary membranous nephropathy. NELL-1–positive membranous nephropathy was more common than THSD7A-positive membranous nephropathy in PLA2R-negative membranous nephropathy.

Routine immunohistochemical staining in membranous nephropathy: in situ detection of phospholipase A2 receptor and thrombospondin type 1 containing 7A domain

2018 ◽  
Vol 31 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Vincenzo L’Imperio ◽  
Federico Pieruzzi ◽  
Renato Alberto Sinico ◽  
Manuela Nebuloni ◽  
Antonio Granata ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Immunohistochemical Staining ◽  
Phospholipase A2 Receptor ◽  
In Situ Detection

scholarly journals Membranous nephropathy associated with viral infection

2020 ◽  
Author(s):  
Aikaterini Nikolopoulou ◽  
Catarina Teixeira ◽  
H Terry Cook ◽  
Candice Roufosse ◽  
Thomas H D Cairns ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Viral Infection ◽  
Membranous Nephropathy ◽  
Spontaneous Remission ◽  
Outcome Data ◽  
Phospholipase A2 Receptor ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Hepatitis Infection

Abstract Background Membranous nephropathy (MN) can be associated with hepatitis infection and less commonly with human immunodeficiency virus (HIV) infection. The significance of anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibodies in this setting is unclear. Methods We describe the clinical, histopathological and outcome data of 19 patients with MN and hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection identified through our renal biopsy database and the association with anti-PLA2R antibodies and anti-THSD7A antibodies. Results The cohort consisted of 19 patients, 8 male and 11 female, with a median age of 42 years (range 23–74). HBV infection was found in six cases, HCV in four and HIV in nine (two HIV patients had HBV co-infection and one HCV co-infection). PLA2R staining on biopsy was positive in 10/19 patients: 4 with HBV-MN, 3 with HCV-MN and 3 with HIV-MN and circulating anti-PLA2R antibodies were detected in 7/10 cases. THSD7A staining on biopsy was positive in three PLA2R-negative cases, one with HBV-MN and two with HIV-MN. Mean proteinuria was higher in the PLA2R-positive group and the median urinary protein:creatinine ratio (uPCR) was 963 mg/mmol (range 22–2406) compared with the PLA2R-negative group [median uPCR 548 mg/mmol (range 65–1898); P = 0.18 Mann–Whitney]. Spontaneous remission occurred in 6/19 patients and after-treatment remission occurred in 7/11 patients. Renal function was preserved in all but two patients who required haemodialysis 2 and 11 years from diagnosis. Conclusions We describe a cohort of patients with MN associated with viral infection, including rare cases of HIV-MN with PLA2R and THSD7A positivity. The mechanism of coincidental or viral-related MN needs to be investigated further.

scholarly journals Exostosin 1/Exostosin 2–Associated Membranous Nephropathy

2019 ◽  
Vol 30 (6) ◽  
pp. 1123-1136 ◽  
Author(s):  
Sanjeev Sethi ◽  
Benjamin J. Madden ◽  
Hanna Debiec ◽  
M. Cristine Charlesworth ◽  
LouAnn Gross ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Membranous Nephropathy ◽  
Validation Cohort ◽  
Laser Microdissection ◽  
Immunohistochemistry Staining ◽  
Phospholipase A2 Receptor ◽  
And Control

BackgroundIn membranous nephropathy (MN), which is characterized by deposition of immune complexes along the glomerular basement membrane (GBM), phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain–containing 7A are target antigens in approximately 70% and 1%–5% of cases of primary MN, respectively. In other cases of primary MN and in secondary MN, the target antigens are unknown.MethodsWe studied 224 cases of biopsy-proven PLA2R-negative MN and 102 controls (including 47 cases of PLA2R-associated MN) in pilot and discovery cohorts. We also evaluated 48 cases of PLA2R-negative presumed primary MN and lupus MN in a validation cohort. We used laser microdissection and mass spectrometry to identify new antigens, which were localized by immunohistochemistry.ResultsMass spectrometry detected exostosin 1 (EXT1) and exostosin 2 (EXT2) in 21 cases of PLA2R-negative MN, but not in PLA2R-associated MN and control cases. Immunohistochemistry staining revealed bright granular GBM staining for EXT1 and EXT2. Clinical and biopsy findings showed features of autoimmune disease, including lupus, in 80.7% of the 26 EXT1/EXT2-associated MN cases we identified. In the validation cohort, we confirmed that EXT1/EXT2 staining was detected in pure class 5 lupus nephritis (eight of 18 patients) and in presumed primary MN associated with signs of autoimmunity (three of 16 patients); only one of the 14 cases of mixed class 5 and 3/4 lupus nephritis was positive for EXT1/EXT2. Tests in seven patients with EXT1/EXT2-associated MN found no circulating anti-exostosin antibodies.ConclusionsA subset of MN is associated with accumulation of EXT1 and EXT2 in the GBM. Autoimmune disease is common in this group of patients.

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