PLA2R antibodies, glomerular PLA2R deposits and variations inPLA2R1andHLA-DQA1genes in primary membranous nephropathy in South Asians

Ramachandran, Raja; Kumar, Vinod; Kumar, Ashwani; Yadav, Ashok; Nada, Ritambhra; Kumar, Harsha; Kumar, Vivek; Rathi, Manish; Kohli, Harbir Singh; Gupta, Krishan Lal; Sakhuja, Vinay; Jha, Vivekanand

doi:10.1093/ndt/gfv399

Cited by 87 publications

(131 citation statements)

References 19 publications

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“…In another study of 114 newly diagnosed pMN patients from India, Ramachandran et al found, 66.7% anti-PLA 2 R positivity (by ELISA) (24). Lower prevalence in our study may be explained by the fact that we included patients with relapse and refractory disease in our study group.…”

Section: Discussioncontrasting

confidence: 54%

Anti-phospholipase A2 receptor antibody in membranous nephropathy; an Indian experience

Yachha¹,

Sharma²,

Mehrotra³

et al. 2017

J Renal Inj Prev

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Section: Discussioncontrasting

confidence: 54%

Anti-phospholipase A2 receptor antibody in membranous nephropathy; an Indian experience

Yachha¹,

Sharma²,

Mehrotra³

et al. 2017

J Renal Inj Prev

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“…They corroborated a highly significant association between pMN and the risk alleles of HLA-DQA1 and PLA2R1 [59-61]. Furthermore, in a Chinese cohort, Lv et al [60] noted gene-gene interactions between the 2 risk alleles and discovered an association between carrying risk alleles and the presence of anti-PLA2R antibodies in serum as well as the expression of PLA2R in glomeruli.…”

Section: Genetic Studies Of Pmnmentioning

confidence: 74%

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

2018

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Background: Primary membranous nephropathy (pMN) is the most common cause of nephrotic syndrome in adults. The discovery of the 2 autoantigens, M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A), has defined pMN as an autoimmune disease. A remarkable increase in the frequency of pMN in primary glomerular disease was witnessed in China. The genetic and environmental contributors to disease susceptibility have been investigated in these patients. Summary: We reviewed recent publications in genetic and environmental studies of pMN, focusing mainly on those undertaken in China. Following a genome-wide association study, the gene-gene interaction between the 2 most significant risk factors, PLA2R1 and DQA1, was validated in Chinese patients with MN. Fine mapping on human leukocyte antigen (HLA) locus found that DRB1*1501 and DRB1*0301 were risk alleles. Three amino acid residues on positions 13 and 71 of HLA-DRβ1 chain may confer the susceptibility to pMN by presenting T-cell epitopes on PLA2R. Another study found that DRB3*0202 was the most likely culprit allele for the signal at DRB1*0301. One environmental risk factor for pMN has been identified as the long-term exposure to high levels of PM_2.5 in Chinese patients with MN. Each 10 μg/m³ increase in PM_2.5 concentration was associated with 14% higher odds for pMN in the regions with PM_2.5 above 70 μg/m³. Key Message: A gene-environment interaction is suspected as an underlying mechanism for the increasing trend of pMN in China.

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“…Recent studies following this paper selected several SNPs as representative from PLA2R1 and the HLA regions791011. The diversity of HLA genes is well-known in human genetics and tightly bound to disease appearance and severity.…”

Section: Discussionmentioning

confidence: 99%

High-density Association Mapping and Interaction Analysis of PLA2R1 and HLA Regions with Idiopathic Membranous Nephropathy in Japanese

Thiri

Honda

Kashiwase

et al. 2016

Sci Rep

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Although recent studies showed anti-PLA2R antibody plays a crucial role in idiopathic membranous nephropathy (IMN), detailed HLA mapping and interaction between the HLA genes and PLA2R1 have not been investigated in IMN. We genotyped across the PLA2R1 gene and the HLA region, using 183 IMN patients and 811 healthy controls. Five SNPs around the PLA2R1 gene were significantly associated with IMN. In addition to the two SNPs previously reported to be strongly associated with IMN, rs3749119 and rs35771982 (OR 3.02 and 2.93, P = 3.24E-14 and 4.64E-14, respectively), two novel intronic SNPs (rs2715928 and rs16844715) were also identified as IMN-associated SNPs (OR = 2.30 and 2.51, P = 3.15E-10 and 5.66E-13, respectively). In the HLA gene analysis, DRB1*1501 and DQB1*0602 were strongly associated with IMN (P = 1.14E-11 and 1.25E-11, respectively). The interaction was strongest between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the intronic SNP rs2715928 (OR = 17.53, P = 4.26E-26). Furthermore, positive interaction was also observed between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the missense SNP rs35771982 (OR = 15.91, P = 2.76E-29), which is in strong linkage disequilibrium with 5′UTR SNP rs3749119, and intronic SNP rs16844715 (OR = 15.91, P = 2.30E-26) for IMN. Neither HLA-DRB1*15:01 nor HLA-DQB1*06:02 was associated with steroid responsiveness, overall survival and renal survival during the observation period of mean 11 years though limited number of analysis.

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PLA₂R antibodies, glomerular PLA₂R deposits and variations inPLA2R1andHLA-DQA1genes in primary membranous nephropathy in South Asians

Abstract: To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy.

Cited by 87 publications

References 19 publications

Anti-phospholipase A2 receptor antibody in membranous nephropathy; an Indian experience

Anti-phospholipase A2 receptor antibody in membranous nephropathy; an Indian experience

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

High-density Association Mapping and Interaction Analysis of PLA2R1 and HLA Regions with Idiopathic Membranous Nephropathy in Japanese

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