Abstracts
During the last decade, several major breakthroughs have led to the identification of human podocyte membrane antigens. Experimental involving antipodocyte antibodies in human membranous nephropathy (MN) have opened a new line of thinking about this disease, relating as an autoimmune kidney disease. In this setting, the M-type phospholipase A2 receptor (PLA2R) was identified as the first major antigen target in human primary MN. Studies have demonstrated anti-PLA2R antibodies against PLA2R ranging from 70 to 89% in patients with MN, but not in those with secondary MN. It has been suggested that the serum level of anti-PLA2R could be used for the diagnosis of idiopathic MN and for the monitoring of response to treatment. However, the coexistence of autoantibodies suggests a complex pathogenic pathway that involves different podocyte targets. New experimental models are needed to elucidate the appearance time and the role of each anti-podocyte antibody in MN development and progression.
autoimmune diseases; glomerulonephritis membranous; receptors; phospholipase A2
Avanços dos conhecimentos moleculares na última década têm permitido a identificação de proteínas podocitárias que atuariam como alvos antigênicos na glomerulonefrite membranosa (GNM). Estudos envolvendo anticorpos contra estruturas podocitárias tem promovido o conceito autoimune da forma idiopática desta glomerulopatia. Neste contexto, o receptor de fosfolipase A2 do tipo M (PLA2R) tem merecido destaque como o primeiro e mais importante autoantígeno descrito na GNM idiopática humana. A presença do anticorpo anti-PLA2R tem sido destacada entre 70% e 89% de portadores da GNM idiopática, diferenciando das formas secundárias. Diversos estudos têm sugerido a detecção do anti-PLA2R como diagnóstico e apontado a correlação de seus níveis circulantes com a atividade clínica e resposta terapêutica. Entretanto, a coexistência de outros autoanticorpos sugere uma complexa via patogênica envolvendo diferentes antígenos podocitários. Estudos adicionais são necessários para esclarecer o tempo de aparecimento e o papel de cada anticorpo antipodócito no diagnóstico e progressão da GNM.
doenças autoimunes; glomerulonefrite membranosa; receptores da fosfolipase A2
Glomerulopathies are the third leading cause of chronic kidney disease among those who
start dialysis in Brazil. 11. Sesso RCC, Lopes AA, Thomé FS, Lugon JR, Watanabe Y, Santos DR.
Diálise crônica no Brasil - Relatório do Censo Brasileiro de Diálise, 2011. J Bras
Nefrol 2012;34:272-7. DOI:
http://dx.doi.org/10.5935/0101-2800.20120009
http://dx.doi.org/10.5935/0101-2800.2012...
A retrospective
epidemiological analysis, involving 9,617 renal biopsies performed in Brazil, revealed
membranous glomerulonephritis (MGN) as the second most prevalent primary glomerular
lesion reaching 20.7% of all the patients. 22. Polito MG, de Moura LA, Kirsztajn GM. An overview on frequency of
renal biopsy diagnosis in Brazil: clinical and pathological patterns based on 9,617
native kidney biopsies. Nephrol Dial Transplant 2010;25:490-6. DOI:
http://dx.doi.org/10.1093/ndt/gfp355
http://dx.doi.org/10.1093/ndt/gfp355...
This
glomerulopathy has the histological characteristic of lacking significant
hypercellularity, and the electron microscopy shows subepithelial/intramembranous immune
deposits (immunoglobulin G and complement), which cause podocyte damage and usually
nephrotic syndrome. MGN can take an idiopathic form without any associated disease
(70%-80%), or it can be secondary to various clinical conditions, including infections
(hepatitis, syphilis), systemic lupus erythematosus, malignancy or it can be
drug-induced. 33. Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a
50-year odyssey. Am J Kidney Dis 2010;56:157-67. DOI:
http://dx.doi.org/10.1053/j.ajkd.2010.01.008
http://dx.doi.org/10.1053/j.ajkd.2010.01...
Histological features found in
electronic analysis and immunofluorescence may be useful in distinguishing idiopathic
(primary) from secondary forms of the disease; however, their clinical and laboratory
presentations are indistinguishable. The lack of understanding of the mechanisms
involved in the pathogenesis of MGN is transmitted to its therapeutic management. To
date, nonspecific severity criteria are the hallmarks of adopted treatment approaches.
44. Waldman M, Austin HA 3rd. Treatment of idiopathic membranous
nephropathy. J Am Soc Nephrol 2012;23:1617-30. DOI:
http://dx.doi.org/10.1681/ASN.2012010058
http://dx.doi.org/10.1681/ASN.2012010058...
The understanding of the MGN pathogenic mechanisms is based on the experimental animal
studies described by Heymann for over five decades. The Heymann nephritis was produced
after injection of kidney extracts in rats. This antigenic preparation caused podocyte
glomerular damage and proteinuria similar to human MGN; it also introduced the concept
of an autologous autoimmune pathogenic complex associated with the MGN. In the animal
model described, podocyte antigenic targets identified as megalin, would be responsible
for in situ immunocomplexes. 55. Heymann W, Hackel DB, Harwood J, Wilson SG, Hunter JL. Production of
nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc
Exp Biol Med 1959;100:660-4. DOI:
http://dx.doi.org/10.3181/00379727-100-24736
http://dx.doi.org/10.3181/00379727-100-2...
However, this antigen is not expressed in human podocytes. From these bases,
anti-podocyte antibodies have been extensively investigated. Podocytes are highly
specialized cells and play a crucial role in the glomerular barrier. Changes to its
surface molecules may cause an immune response with antibody binding, complement
activation and cell damage. Podocyte retraction causes proteinuria, glomerular barrier
destruction and starts progression to chronic kidney disease.
Advances in molecular knowledge in the last decade have allowed the identification of
podocyte proteins that act as potential antigenic targets for in situ
formation of immune deposits, explaining the concept of "podocytopathy". In this field
of study, human podocyte targets have been identified and held accountable as
autoantigens. Two major antigens, both membrane glycoproteins, deserve highlighting: in
2002, Hanna Debiec and Pierre Ronco's group studied a rare form of antenatal MGN and
found the neutral endopeptidase (NEP) - metallopeptidase 94 kDa, which is located on the
cell surface of podocytes. 66. Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann JP, Bensman A,
et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase
antibodies. N Engl J Med 2002;346:2053-60. PMID: 12087141 DOI:
http://dx.doi.org/10.1056/NEJMoa012895
http://dx.doi.org/10.1056/NEJMoa012895...
The disease can be
transferred to animals by injecting immunoglobulins extracted from the serum of children
(anti-NEP) with this condition, which is an aloimmunization. 77. Ronco P, Debiec H. Molecular pathomechanisms of membranous
nephropathy: from Heymann nephritis to alloimmunization. J Am Soc Nephrol
2005;16:1205-13. DOI: http://dx.doi.org/10.1681/ASN.2004121080
http://dx.doi.org/10.1681/ASN.2004121080...
A second antigen was described in 2009 by Beck et al.
88. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et
al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous
nephropathy. N Engl J Med 2009;361:11-21. PMID: 19571279 DOI:
http://dx.doi.org/10.1056/NEJMoa0810457
http://dx.doi.org/10.1056/NEJMoa0810457...
, the M-type A2 phospholipase
receptor (PLA2R) - a protein with 185 kDa expressed in human podocytes. The activation
of this receptor causes a pathogenic pathway with complement activation and cell damage.
Using immunoenzymatic assays (Western blotting), human glomerular proteins were added to
serum samples from patients with idiopathic and secondary MGN, and other
glomerulopathies (IgA, diabetic nephropathy). Thus, it was possible to find the specific
reactivity against a protein of 185 kDa in 70% of samples from idiopathic MGN.
Subsequently, these antigenic targets had their epitopes identified with the same
sensitivity to antibodies directed against PLA2R (anti-PLA2R),
predominantly of subclass 4 (IgG4). Immunohistochemical techniques made it possible to
locate the expression of this antigen between the urinary space and the basement
membrane prominently in podocytes. After the description of this autoantigen, relevant
publications have highlighted the presence of anti-PLA2R; with specificity
ranging from 57% to 89% in patients with idiopathic MGN. 99. Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, et al.
Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol
2011;22:1137-43. DOI: http://dx.doi.org/10.1681/ASN.2010090967
http://dx.doi.org/10.1681/ASN.2010090967...
10. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular
deposits in membranous nephropathy. N Engl J Med 2011;364:689-90. PMID: 21323563 DOI:
http://dx.doi.org/10.1056/NEJMc1011678
http://dx.doi.org/10.1056/NEJMc1011678...
11. Hoxha E, Harendza S, Zahner G, Panzer U, Steinmetz O, Fechner K, et
al. An immunofluorescence test for phospholipase-A2-receptor antibodies and its
clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial
Transplant 2011;26:2526-32. DOI:
http://dx.doi.org/10.1093/ndt/gfr247
http://dx.doi.org/10.1093/ndt/gfr247...
-1212. Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ.
Anti-phospholipase A2 receptor antibodies correlate with clinical status in
idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011;6:1286-91. DOI:
http://dx.doi.org/10.2215/CJN.07210810
http://dx.doi.org/10.2215/CJN.07210810...
Anti-PLA2R
positivity was demonstrated (Western blotting) in 81.7% of blood samples from 60 Chinese
patients with idiopathic MGN and proteinuria greater than 3.5g/24h. 99. Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, et al.
Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol
2011;22:1137-43. DOI: http://dx.doi.org/10.1681/ASN.2010090967
http://dx.doi.org/10.1681/ASN.2010090967...
Deepening the anti-PLA2R research, Debiec et al. 1010. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular
deposits in membranous nephropathy. N Engl J Med 2011;364:689-90. PMID: 21323563 DOI:
http://dx.doi.org/10.1056/NEJMc1011678
http://dx.doi.org/10.1056/NEJMc1011678...
studied PLA2R immune deposits in renal
tissue (glomeruli) of 42 patients with MGN without evidence of secondary forms. These
patients had blood and tissue samples collected prior to the immunosuppressive therapy.
The anti-PLA2R serum sensitivity and the study of PLA2R in
glomeruli was 57% and 74%, respectively. In 10 anti-PLA2R serum-negative
patients we found PLA2R glomerular deposits. These observations showed that
establishing scenarios: glomerular tissue and serum could stratify different stages of
the disease. A quicker serum clearing and its deposition in renal tissue could explain
this discrepancy. Thus, we extracted important information that the absence of
circulating anti-PLA2R at the time of biopsy would not rule out the diagnosis
of anti-PLA2R-related MGN. The prospective study carried out in Hamburg by
Hoxha et al. 1111. Hoxha E, Harendza S, Zahner G, Panzer U, Steinmetz O, Fechner K, et
al. An immunofluorescence test for phospholipase-A2-receptor antibodies and its
clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial
Transplant 2011;26:2526-32. DOI:
http://dx.doi.org/10.1093/ndt/gfr247
http://dx.doi.org/10.1093/ndt/gfr247...
included 88
patients with histological diagnosis of MGN. In 61 patients (69%), there was a strong
positivity for PLA2R in the glomeruli, with almost identical serum
correlation (anti-PLA2R). Anti-PLA2R was also correlated with the
activity and therapeutic response achieved. It was possible to correlate
anti-PLA2R levels with proteinuria reduction in patients receiving
anti-CD20 monoclonal antibody (rituximab), suggesting anti-PLA2R monitoring
as a tool for treatment decision making. High levels of anti-PLA2R would be
associated with disease activity (proteinuria) and increased risk of decline in renal
function. 1212. Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ.
Anti-phospholipase A2 receptor antibodies correlate with clinical status in
idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011;6:1286-91. DOI:
http://dx.doi.org/10.2215/CJN.07210810
http://dx.doi.org/10.2215/CJN.07210810...
One issue that has also been discussed is the different risks detected in subgroups
determined by HLA DQA1, which would expose populations to greater susceptibility to MGN.
1313. Kanigicherla D, Gummadova J, McKenzie EA, Roberts SA, Harris S,
Nikam M, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in
a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int
2013;83:940-8. DOI: http://dx.doi.org/10.1038/ki.2012.486
http://dx.doi.org/10.1038/ki.2012.486...
,1414. Lv J, Hou W, Zhou X, Liu G, Zhou F, Zhao N, et al. Interaction
between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and
membranous nephropathy. J Am Soc Nephrol 2013;24:1323-9. DOI:
http://dx.doi.org/10.1681/ASN.2012080771
http://dx.doi.org/10.1681/ASN.2012080771...
PLA2R polymorphism can add clarification to this individual MGN
susceptibility. The study by Liu et al. 1515. Liu YH, Chen CH, Chen SY, Lin YJ, Liao WL, Tsai CH, et al.
Association of phospholipase A2 receptor 1 polymorphisms with idiopathic membranous
nephropathy in Chinese patients in Taiwan. J Biomed Sci 2010;17:81. DOI:
http://dx.doi.org/10.1186/1423-0127-17-81
http://dx.doi.org/10.1186/1423-0127-17-8...
demonstrated that the rs35771982 SNPs (single nucleotide polymorphisms)
would have a more selective expression in Chinese population with MGN. The frequency of
the G allele at rs35771982 and the G/G genotype of this SNP are even associated with the
low rate of MGN remission. A European study, after isolating the DNA and genotyping 556
patients (French, Dutch and English) with idiopathic MGN, suggested the hypothesis that
there would be "high risk" PLA2R for alloimmunization. These results show a
close relationship between idiopathic MGN and HLA-DQA1 and PLA2R risk
alleles. 1616. Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A,
Dragomirescu L, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous
nephropathy. N Engl J Med 2011;364:616-26. PMID: 21323541 DOI:
http://dx.doi.org/10.1056/NEJMoa1009742
http://dx.doi.org/10.1056/NEJMoa1009742...
MGN may recur in up to 42% of renal transplant recipients. The initial symptoms are
subtle, but evolve with proteinuria and graft loss. 1717. Dabade TS, Grande JP, Norby SM, Fervenza FC, Cosio FG. Recurrent
idiopathic membranous nephropathy after kidney transplantation: a surveillance biopsy
study. Am J Transplant 2008;8:1318-22. PMID: 18444918 DOI:
http://dx.doi.org/10.1111/j.1600-6143.2008.02237.x
http://dx.doi.org/10.1111/j.1600-6143.20...
Rituximab is effective in the treatment of post-transplant MGN relapse,
including regression of immune deposits. 1818. El-Zoghby ZM, Grande JP, Fraile MG, Norby SM, Fervenza FC, Cosio FG.
Recurrent idiopathic membranous nephropathy: early diagnosis by protocol biopsies and
treatment with anti-CD20 monoclonal antibodies. Am J Transplant 2009;9:2800-7. DOI:
http://dx.doi.org/10.1111/j.1600-6143.2009.02851.x
http://dx.doi.org/10.1111/j.1600-6143.20...
Debiec et al. 1919. Debiec H, Hanoy M, Francois A, Guerrot D, Ferlicot S, Johanet C, et
al. Recurrent membranous nephropathy in an allograft caused by IgG3? targeting the
PLA2 receptor. J Am Soc Nephrol 2012;23:1949-54. DOI:
http://dx.doi.org/10.1681/ASN.2012060577
http://dx.doi.org/10.1681/ASN.2012060577...
reported a case
of post-transplant MGN recurrence, in which the biopsy showed PLA2R
subepithelial glomerular deposits in both the graft and the native kidneys. Treatment
with rituximab stabilized proteinuria and serum creatinine levels; in addition,
anti-PLA2R serum levels became undetectable. In this exceptionally early
recurrence report, there was IgG3 subclass and also complement activation via MBL
(lecithin). The detection of PLA2R immune deposits in the biopsy samples may
be, at present, more sensitive than serological tests to evaluate anti-PLA2R
mediated-MGN. 2020. Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H. Kidney biopsy is
a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy.
Nephrol Dial Transplant 2013;28:1839-44. DOI:
http://dx.doi.org/10.1093/ndt/gfs439
http://dx.doi.org/10.1093/ndt/gfs439...
PLA2R is naturally expressed on podocyte cell membranes and acts as a
phospholipase A2 (PLA2) receptor. This receptor participates in the
regulation of PLA2R biological responses involving cell proliferation,
adhesion, production of lipid mediators, and the release of arachidonic acid.
Oncogenetic studies implicate PLA2R as a multifunctional receptor; changes in
the expression of this receptor have a major impact on human cell senescence via
generation of reactive oxygen species. The signaling for cell injury could follow the
p-53 path, a protein that plays a central role in cellular response, including cell
cycle arrest, allowing DNA damage repair or cell death induction. 2121. Augert A, Payré C, de Launoit Y, Gil J, Lambeau G, Bernard D. The
M-type receptor PLA2R regulates senescence through the p53 pathway. EMBO Rep
2009;10:271-7. DOI: http://dx.doi.org/10.1038/embor.2008.255
http://dx.doi.org/10.1038/embor.2008.255...
The harmful steps that follow the link to the target antigen (PLA2R) would
lead to additional expression of a number of secondary cytoplasmic autoantigens
(AR-aldose reductase, 2-SOD2 superoxide dismutase and α-enolase) also described in
idiopathic MGN without circulating anti-PLA2R. In 50% of patients with MGN -
non-responders or partial responders to therapy, serum anti-AR and anti-SOD2 were found,
turning more intriguing the understanding of the MGN autoimmune character. Additional
studies will be needed to clarify the stage of appearance and the role of each
anti-podocyte antibody on MGN onset and progression. 2222. Murtas C, Bruschi M, Candiano G, Moroni G, Magistroni R, Magnano A,
et al. Coexistence of different circulating anti-podocyte antibodies in membranous
nephropathy. Clin J Am Soc Nephrol 2012;7:1394-400. DOI:
http://dx.doi.org/10.2215/CJN.02170312
http://dx.doi.org/10.2215/CJN.02170312...
Given the cumulative evidence, we gathered arguments to elect anti-PLA2R as a
glomerular biomarker. It is measurable, it reports on the state of a pathological
process and on the clinical/laboratory response vis-à-vis the drug therapy. 2323. McMahon GM, Waikar SS. Biomarkers in nephrology: Core Curriculum
2013. Am J Kidney Dis 2013;62:165-78. DOI:
http://dx.doi.org/10.1053/j.ajkd.2012.12.022
http://dx.doi.org/10.1053/j.ajkd.2012.12...
However, further prospective studies with
different immunoglobulin subclasses are needed in order to elucidate the complement's
role, to let us go deeper in the mechanism of this autoimmune disease. It is also
necessary to unravel the role of the various antigenic podocyte targets described. 2424. Prunotto M, Carnevali ML, Candiano G, Murtas C, Bruschi M, Corradini
E, et al Autoimmunity in membranous nephropathy targets aldose reductase and SOD2. J
Am Soc Nephrol 2010;21:507-19. DOI:
http://dx.doi.org/10.1681/ASN.2008121259
http://dx.doi.org/10.1681/ASN.2008121259...
Studies with laser microdissection and proteomics
will help elucidate the complex intracellular sequence of antigenic stimulation. We may
correlate evolutionary MGN stages with the detection of specific antibodies in
circulation and proper drug therapy. 2525. Bruschi M, Carnevali ML, Murtas C, Candiano G, Petretto A, Prunotto
M, et al. Direct characterization of target podocyte antigens and auto-antibodies in
human membranous glomerulonephritis: Alfa-enolase and borderline antigens. J
Proteomics 2011;74:2008-17. PMID: 21640210 DOI:
http://dx.doi.org/10.1016/j.jprot.2011.05.021
http://dx.doi.org/10.1016/j.jprot.2011.0...
Referências
-
1Sesso RCC, Lopes AA, Thomé FS, Lugon JR, Watanabe Y, Santos DR. Diálise crônica no Brasil - Relatório do Censo Brasileiro de Diálise, 2011. J Bras Nefrol 2012;34:272-7. DOI: http://dx.doi.org/10.5935/0101-2800.20120009
» http://dx.doi.org/10.5935/0101-2800.20120009 -
2Polito MG, de Moura LA, Kirsztajn GM. An overview on frequency of renal biopsy diagnosis in Brazil: clinical and pathological patterns based on 9,617 native kidney biopsies. Nephrol Dial Transplant 2010;25:490-6. DOI: http://dx.doi.org/10.1093/ndt/gfp355
» http://dx.doi.org/10.1093/ndt/gfp355 -
3Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis 2010;56:157-67. DOI: http://dx.doi.org/10.1053/j.ajkd.2010.01.008
» http://dx.doi.org/10.1053/j.ajkd.2010.01.008 -
4Waldman M, Austin HA 3rd. Treatment of idiopathic membranous nephropathy. J Am Soc Nephrol 2012;23:1617-30. DOI: http://dx.doi.org/10.1681/ASN.2012010058
» http://dx.doi.org/10.1681/ASN.2012010058 -
5Heymann W, Hackel DB, Harwood J, Wilson SG, Hunter JL. Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med 1959;100:660-4. DOI: http://dx.doi.org/10.3181/00379727-100-24736
» http://dx.doi.org/10.3181/00379727-100-24736 -
6Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann JP, Bensman A, et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med 2002;346:2053-60. PMID: 12087141 DOI: http://dx.doi.org/10.1056/NEJMoa012895
» http://dx.doi.org/10.1056/NEJMoa012895 -
7Ronco P, Debiec H. Molecular pathomechanisms of membranous nephropathy: from Heymann nephritis to alloimmunization. J Am Soc Nephrol 2005;16:1205-13. DOI: http://dx.doi.org/10.1681/ASN.2004121080
» http://dx.doi.org/10.1681/ASN.2004121080 -
8Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009;361:11-21. PMID: 19571279 DOI: http://dx.doi.org/10.1056/NEJMoa0810457
» http://dx.doi.org/10.1056/NEJMoa0810457 -
9Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 2011;22:1137-43. DOI: http://dx.doi.org/10.1681/ASN.2010090967
» http://dx.doi.org/10.1681/ASN.2010090967 -
10Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med 2011;364:689-90. PMID: 21323563 DOI: http://dx.doi.org/10.1056/NEJMc1011678
» http://dx.doi.org/10.1056/NEJMc1011678 -
11Hoxha E, Harendza S, Zahner G, Panzer U, Steinmetz O, Fechner K, et al. An immunofluorescence test for phospholipase-A2-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant 2011;26:2526-32. DOI: http://dx.doi.org/10.1093/ndt/gfr247
» http://dx.doi.org/10.1093/ndt/gfr247 -
12Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ. Anti-phospholipase A2 receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011;6:1286-91. DOI: http://dx.doi.org/10.2215/CJN.07210810
» http://dx.doi.org/10.2215/CJN.07210810 -
13Kanigicherla D, Gummadova J, McKenzie EA, Roberts SA, Harris S, Nikam M, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int 2013;83:940-8. DOI: http://dx.doi.org/10.1038/ki.2012.486
» http://dx.doi.org/10.1038/ki.2012.486 -
14Lv J, Hou W, Zhou X, Liu G, Zhou F, Zhao N, et al. Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy. J Am Soc Nephrol 2013;24:1323-9. DOI: http://dx.doi.org/10.1681/ASN.2012080771
» http://dx.doi.org/10.1681/ASN.2012080771 -
15Liu YH, Chen CH, Chen SY, Lin YJ, Liao WL, Tsai CH, et al. Association of phospholipase A2 receptor 1 polymorphisms with idiopathic membranous nephropathy in Chinese patients in Taiwan. J Biomed Sci 2010;17:81. DOI: http://dx.doi.org/10.1186/1423-0127-17-81
» http://dx.doi.org/10.1186/1423-0127-17-81 -
16Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med 2011;364:616-26. PMID: 21323541 DOI: http://dx.doi.org/10.1056/NEJMoa1009742
» http://dx.doi.org/10.1056/NEJMoa1009742 -
17Dabade TS, Grande JP, Norby SM, Fervenza FC, Cosio FG. Recurrent idiopathic membranous nephropathy after kidney transplantation: a surveillance biopsy study. Am J Transplant 2008;8:1318-22. PMID: 18444918 DOI: http://dx.doi.org/10.1111/j.1600-6143.2008.02237.x
» http://dx.doi.org/10.1111/j.1600-6143.2008.02237.x -
18El-Zoghby ZM, Grande JP, Fraile MG, Norby SM, Fervenza FC, Cosio FG. Recurrent idiopathic membranous nephropathy: early diagnosis by protocol biopsies and treatment with anti-CD20 monoclonal antibodies. Am J Transplant 2009;9:2800-7. DOI: http://dx.doi.org/10.1111/j.1600-6143.2009.02851.x
» http://dx.doi.org/10.1111/j.1600-6143.2009.02851.x -
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Publication Dates
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Publication in this collection
Jan-Mar 2014
History
-
Received
03 Oct 2013 -
Accepted
08 Oct 2013