The immunohistological profile of membranous nephropathy associated with syphilis infection

Wanderley, David Campos; Neves, Precil Diego Miranda de Menezes; Jorge, Lectícia Barbosa; Onuchic, Luiz Fernando; Araújo, Stanley Almeida

doi:10.1093/ckj/sfab057

Cited by 6 publications

(3 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[33][34][35] A recent report has also shown PLA2R positive staining by IHC in four out of ten cases of syphilisassociated MN. 6 Two out of the four PLA2R-positive cases may represent primary MN because they stained for IgG4 and not IgG1. Serum was not tested for anti-PLA2R antibody in any case.…”

Section: Discussionmentioning

confidence: 95%

“…[15][16][17][18][19][20][21][22] In most cases of syphilis-associated MN, the target antigen is not known, although PLA2R has been identified in a few cases. 6 We have previously performed MS/MS studies to identify novel target antigens in PLA2R-negative MN, which include EXT1/EXT2, NELL1, SEMA3B, PCDH7, and FAT1. Using similar methodology, we now show that a novel protein, NDNF, is the target antigen in syphilis-associated MN.…”

Section: Introductionmentioning

confidence: 99%

“…1 MN is the most common cause of nephrotic syndrome in syphilis, although it has been reported in only small series or case reports. [4][5][6][7][8][9] MN is characterized by accumulation of immune complexes in the subepithelial region along glomerular basement membranes (GBM). [10][11][12] MN is often classified into primary MN, where there is no identifiable underlying disease association, and secondary MN, where MN may be associated with an autoimmune disease, infections such as hepatitis and syphilis, malignancy, hematopoietic stem cell transplant, drugs, etc.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Membranous Nephropathy in Syphilis is Associated with Neuron-Derived Neurotrophic Factor

Sethi

Madden

Moura

et al. 2023

JASN

View full text Add to dashboard Cite

Background Syphilis is a common sexually transmitted infection. Membranous nephropathy (MN) is a common cause of proteinuria in syphilis. The target antigen is not known in most cases of syphilis-associated MN. MethodsWe performed laser microdissection of glomeruli and mass spectrometry (MS/MS) in 250 cases (discovery cohort) of phospholipase A2 receptor-negative MN to identify novel target antigens. This was followed by immunohistochemistry/ confocal microscopy to localize the target antigen along the glomerular basement membrane (GBM). Western blot analyses using IgG eluted from frozen biopsy tissue were performed to detect binding to target antigen.Results MS/MS studies of the discovery cohort revealed high total spectral counts of a novel protein, neuron-derived neurotrophic factor (NDNF), in three patients: one each with syphilis and hepatitis B, HIV (syphilis status not known), and lung tumor. Next, MS/MS studies of five cases of syphilis-MN (validation cohort) confirmed high total spectral counts of NDNF (average 45620.4) in all (100%) cases. MS/MS of 14 cases of hepatitis B were negative for NDNF. All eight cases of NDNFassociated MN were negative for known MN antigens. Electron microscopy showed stage I MN in all cases, with superficial and hump-like deposits without GBM reaction. IgG1 was the dominant IgG subtype on MS/MS and immunofluorescence microscopy. Immunohistochemistry/confocal microscopy showed granular staining and colocalization of NDNF and IgG along GBM. Western blot analyses using eluate IgG of NDNF-MN showed binding to both nonreduced and reduced NDNF, while IgG eluate from phospholipase A2 receptor-MN showed no binding.Conclusion NDNF is a novel antigenic target in syphilis-associated MN.

show abstract