Membranous glomerulonephritis secondary to syphilis

Araújo, Stanley de Almeida; Giordano, Luiz Flávio Couto; Rosa, Ariel Augusto de Britto; Carmo, Paula Alves Santos do; Honorato‐Sampaio, Kinulpe

doi:10.1016/j.bjid.2015.03.003

Cited by 4 publications

(2 citation statements)

References 2 publications

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“…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.…”

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confidence: 99%

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

Sethi

Madden

Moura

et al. 2023

JASN

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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.

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Section: Introductionmentioning

confidence: 99%

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

Sethi

Madden

Moura

et al. 2023

JASN

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“…Syphilis is a sexually transmitted infection caused by Treponema pallidum . Proteinuria in congenital and acquired latent (secondary or tertiary) syphilis has been mostly associated with membranous nephropathy (MN) [ 1 ]. The 10 MN patients in the present study had venereal disease research laboratory positivity confirmed with fluorescent treponemal antibody absorbed after the biopsy diagnosis.…”

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The immunohistological profile of membranous nephropathy associated with syphilis infection

Wanderley

Neves

Jorge

et al. 2021

Clinical Kidney Journal

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Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?

Veloso

Neves²,

Jorge³

et al. 2017

Nephron

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Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders.

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Membranous glomerulonephritis secondary to syphilis

Cited by 4 publications

References 2 publications

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

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

The immunohistological profile of membranous nephropathy associated with syphilis infection

Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?

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