A rare case of PLA2R- and THSD7A-positive idiopathic membranous nephropathy

Wanderley, David Campos; Jones, Bárbara Dornelas; Barbosa, Fabricio Augusto Marques; Araújo, Stanley de Almeida

doi:10.1590/2175-8239-jbn-2019-0077

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…The immunohistochemical PLA2R1 positivity was not expected. These histological findings support that PLA2R1 positivity alone is specific for primary MN, as it is also observed, besides syphilis, in chronic Schistosoma mansoni [ 2 ] infection, membranous lupus nephritis [ 3 ] and cancer [ 4 ]. In this regard, PLA2R1 expression can be increased in podocytes by non-specific inflammatory mediators such as tumour necrosis factor-like weak inducer of apoptosis (TWEAK) [ 5 ].…”

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confidence: 67%

The immunohistological profile of membranous nephropathy associated with syphilis infection

Wanderley

Neves

Jorge

et al. 2021

Clinical Kidney Journal

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supporting

confidence: 67%

The immunohistological profile of membranous nephropathy associated with syphilis infection

Wanderley

Neves

Jorge

et al. 2021

Clinical Kidney Journal

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“…The reported frequencies of occurrence of anti-PLA2R and anti-THSD7A antibodies in MN are 50–80% and 5–10% ( 13 ), respectively; the target antigen of MN is uncertain in 10–20% of cases. The presence of one type of antibody does not exclude the presence of other antibody types, as shown by a reported case of anti-PLA2R- and anti-THSD7A-positive MN ( 34 ). It has been suggested that MGN is secondary to an increase in serum IgG4 concentration, which may be due to the deposition of the circulating immune complexes or other unknown mechanisms.…”

Section: Discussionmentioning

confidence: 95%

Characteristics of Anti-Contactin1 Antibody-Associated Autoimmune Nodopathies With Concomitant Membranous Nephropathy

Liu²,

Zhang

et al. 2021

Front. Immunol.

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BackgroundThe concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN.MethodsWe detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathy via double immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodies via enzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics.ResultsA 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43–78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels.ConclusionThe age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.

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“…We conducted a systematic review of the literature on previous studies involving double antigen-positive IMN. By June 6, 2023, a total of 11 studies (7,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) involving 43 dual antigen-positive IMN patients, were included (Supplementary Table 1, Supplementary Figure 2). Of the 43 patients, highly detailed information was available for only 11, and we extracted clinical, pathological, and prognostic information for these 11 patients (Table 2) and then performed comparisons with the 6 dual antigen-positive IMN patients at our center (Supplementary Table 2).…”

Section: Literature Review and Information Extraction Of Previous Rep...mentioning

confidence: 99%

“…Indeed, many IMN target antigens have been discovered over the past decade, including thrombospondin type 1 domain containing 7A (THSD7A) and neuroepidermal growth factor-like type 1 protein (NELL-1) (4,5). However, the vast majority of IMN patients reported thus far are single antigenpositive; in contrast, dual antigen-positive IMN patients are very rare, with only a few such cases being briefly described in various studies (6)(7)(8). There is no specific study on the clinicopathological and prognostic characteristics of dual antigen-positive IMN patients, and the disease characteristics of such patients remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological and prognostic characteristics of idiopathic membranous nephropathy with dual antigen positivity

Yang,

Wang,

et al. 2024

Front. Immunol.

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BackgroundIdiopathic membranous nephropathy (IMN) is the most common pathological type in adults with nephrotic syndrome. Many target antigens have been discovered. However, dual antigen-positive IMN patients are very rare, with only a few such cases being briefly described in various studies. There is no specific study on the clinicopathological and prognostic characteristics of dual antigen-positive IMN patients, and the disease characteristics of such patients remain unclear.MethodsImmunohistochemical staining of PLA2R, THSD7A, and NELL-1 was conducted on kidney tissue samples obtained from patients diagnosed with IMN. Simultaneously, the presence of corresponding serum antibodies was determined. Patients exhibiting positivity for dual antigens were included in the study, identified either through tissue staining or serum antibody detection. We retrospectively collected their clinical, pathological, and follow-up data and measured their serum antibody levels at multiple time points. Additionally, the same type of dual antigen-positive IMN cases reported in the literature were reviewed to extract clinical, pathological, and prognostic information. We compared the data for all of the above dual antigen-positive and PLA2R single-positive IMN cases at our center.ResultsWe identified 6 IMN patients with dual antigen positivity at our center, approximately 0.7% of whole MN series; the previous literature reports 43 IMN patients with dual antigen positivity, the proportion ranged from 0.2% to 2.8%. The IgG1 positivity rate in the renal tissue of the dual antigen-positive patients at our center was significantly lower than that of dual antigen-positive patients previously reported (16.7% vs. 100.0%, p=0.015), but there was no significant difference in clinical or prognostic aspects. Patients with dual antigen positivity reported at our center and in the literature were combined and compared with PLA2R single-positive IMN reported at our center. Compared with PLA2R single-positive IMN patients, dual antigen-positive IMN patients had a higher renal tissue IgG1 positivity rate (58.3% vs. 22.3%, p=0.016), and the time required to achieve remission was longer [13.5 (3.3,35.0) vs. 3.0 (1.0,8.0), p=0.052]. Overall, The changes in urine protein were consistent with the changes in serum PLA2R antibody levels in dual antigen-positive IMN patients.ConclusionsFor patients with primary membranous nephropathy who did not attain remission following prolonged treatment, multiple target antigen staining should still be actively performed, even with positivity for the PLA2R target antigen.

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A rare case of PLA2R- and THSD7A-positive idiopathic membranous nephropathy

Cited by 5 publications

References 16 publications

The immunohistological profile of membranous nephropathy associated with syphilis infection

The immunohistological profile of membranous nephropathy associated with syphilis infection

Characteristics of Anti-Contactin1 Antibody-Associated Autoimmune Nodopathies With Concomitant Membranous Nephropathy

Clinicopathological and prognostic characteristics of idiopathic membranous nephropathy with dual antigen positivity

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