Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients

Schmitt, J.; Keller, Andreas; Nourkami-Tutdibi, Nasenien; Heisel, Sabrina; Habel, Nunja; Leidinger, Petra; Ludwig, Nicole; Gessler, Manfred; Graf, Norbert; Berthold, Frank; Lenhof, Hans‐Peter; Meese, Eckart

doi:10.1371/journal.pone.0028951

Cited by 7 publications

(8 citation statements)

References 41 publications

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“…Tumor-associated autoantibodies can be used as diagnostic tools. Despite that nephroblastomas have a much lower expression of autoantibodies than neuroblastomas, 72 , 73 differential autoantibody signatures allowed separation between WT patients, neuroblastoma patients, and healthy controls with sensitivity and specificity of more than 86%. 72 In WT patients not subjected to neoadjuvant chemotherapy, the autoantibodies contributing the most to the identification of WT patients were directed to the proteins ZFP 346 and fascin.…”

Section: Neoantigen Productionmentioning

confidence: 99%

Systematic review of the immunological landscape of Wilms tumors

Palmisani

Kovar

Kager

et al. 2021

Molecular Therapy - Oncolytics

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Results of immunotherapy in childhood solid cancer have been so far, with the exception of neuroblastoma, quite disappointing. Lack of knowledge of the immune contexture of these tumors may have contributed to the failure of immunotherapies so far. Here, we systematically reviewed the literature regarding the immunology of Wilms tumor (WT), one of the most frequent pediatric solid tumors of the abdomen. In Wilms tumor patients the high cure rate of >90%, achieved by the combination of surgery and radio-chemotherapy, is at the expense of a high early and late toxicity. Moreover, treatment-resistant entities, such as diffuse anaplastic tumors or recurrent disease, still pose unsolved clinical problems. Successful immunotherapy could represent a novel and possibly less-toxic treatment option. Employing the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) method of literature search, we analyzed the current knowledge of the immunological landscape of Wilms tumors in terms of tumor microenvironment, prognostic implications of single biomarkers, and immunotherapy response.

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Section: Neoantigen Productionmentioning

confidence: 99%

Systematic review of the immunological landscape of Wilms tumors

Palmisani

Kovar

Kager

et al. 2021

Molecular Therapy - Oncolytics

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“…To determine the frequency with which particular peptide clones are recognized by antibodies present in sera from patients with MG vs. healthy controls we used an arbitrarily defined cut-off, considering intensity values of ≥50 as positive and <50 as negative [26], [28]. The frequency of positive sera for a given peptide clone in each group was then calculated according to the formula [(number of sera with intensity values ≥50/(number of sera with intensity values ≥50 + number of sera with intensity values <50)] ×100%.…”

Section: Resultsmentioning

confidence: 99%

“…Evaluation of autoantibody profiles from protein macroarrays is based on the assumption that analysis of patterns of multiple antibody reactivities might be more informative than analysis of single autoantibodies alone [20]. Indeed, previous work performed in patients with various cancers as well as autoimmune diseases suggests that autoantibody profiles may have the potential to serve as disease biomarkers and to provide clues for disease pathogenesis [20], [21], [22], [23], [24], [25], [26]. Accordingly, a customized protein macroarray comprising 1827 potential human autoantigens recently developed in our laboratory permitted to adequately discriminate sera of patients with different cancers from sera of healthy controls [27], [28], [29].…”

Section: Introductionmentioning

confidence: 99%

Myasthenia Gravis: Analysis of Serum Autoantibody Reactivities to 1827 Potential Human Autoantigens by Protein Macroarrays

et al. 2013

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BackgroundMyasthenia gravis is a disorder of neuromuscular transmission associated with autoantibodies against the nicotinic acetylcholine receptor. We have previously developed a customized protein macroarray comprising 1827 potential human autoantigens, which permitted to discriminate sera of patients with different cancers from sera of healthy controls, but has not yet been evaluated in antibody-mediated autoimmune diseases.ObjectiveTo determine whether autoantibody signatures obtained by protein macroarray separate sera of patients with myasthenia gravis from healthy controls.MethodsSera of patients with acetylcholine receptor antibody-positive myasthenia gravis (n = 25) and healthy controls (n = 32) were analyzed by protein macroarrays comprising 1827 peptide clones.ResultsAutoantibody signatures did not separate patients with myasthenia gravis from controls with sufficient sensitivity, specificity, and accuracy. Intensity values of one antigen (poly A binding protein cytoplasmic 1, p = 0.0045) were higher in patients with myasthenia gravis, but the relevance of this and two further antigens, 40S ribosomal protein S13 (20.8% vs. 0%, p = 0.011) and proteasome subunit alpha type 1 (25% vs. 3.1%, p = 0.035), which were detected more frequently by myasthenia gravis than by control sera, currently remains uncertain.ConclusionSeroreactivity profiles of patients with myasthenia gravis detected by a customized protein macroarray did not allow discrimination from healthy controls, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor.

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“…In the field of SRBCT and the overlap of nephroblastoma and neuroblastoma two recent reports propose immunohistochemical markers, cyclin D1 and PHOX2B, to be reliable for distinction of neuroblastoma from other malignancies [ 21 , 22 ]. Different autoantibody signatures obtained from peripheral blood were detected with high sensitivity and specificity in untreated nephroblastoma and neuroblastoma patients, making this approach particularly interesting in the absence of histological samples [ 23 ]. In the case described in this study previous establishment of diagnostic signatures to distinguish SRBCT by gene expression analysis and a multiplex RT-PCR assay, the latter being extended for Wilms’ specific genes, allowed analysis of the patients’ tumor [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Case report: value of gene expression profiling in the diagnosis of atypical neuroblastoma

Harttrampf

Chen

Jüttner³

et al. 2017

BMC Res Notes

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BackgroundNephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in distinguishing between these two entities, especially if unusual variations to prevalent patterns of disease manifestation occur. Because of the risk of tumor rupture, European protocols do not require biopsy for diagnosis, which leads to misdiagnosis in some cases.Case presentationWe report on a 4½-year-old girl with a renal tumor displaying radiological and laboratory characteristics supporting the diagnosis of nephroblastoma. Imaging studies showed tumor extension into the inferior vena cava and bilateral lung metastases while urine catecholamines and MIBG-scintigraphy were negative. Preoperative chemotherapy with vincristine, actinomycine D and adriamycin according to the SIOP2001/GPOH protocol for the treatment of nephroblastoma was initiated and followed by surgical tumor resection. Histopathology revealed an undifferentiated tumor with expression of neuronal markers, suggestive of neuroblastoma. MYCN amplification could not be detected. DNA-microarray analysis was performed using Affymetrix genechip human genome U133 plus 2.0 and artificial neural network analysis. Results were confirmed by multiplex RT-PCR.ResultsPrincipal component analysis using 84 genes showed that the patient sample was clearly clustering with neuroblastoma tumors. This was confirmed by hierarchical clustering of the multiplex RT-PCR data. The patient underwent treatment for high-risk neuroblastoma comprising chemotherapy including cisplatin, etoposide, vindesine, dacarbacine, ifosfamide, vincristine, adriamycine and autologous stem cell transplantation followed by maintenance therapy with 13-cis retinoic acid (GPOH NB2004 High Risk Trial Protocol) and is in complete long-term remission.ConclusionThe use of gene expression profiling in an individual patient strongly contributed to clarification in a diagnostic dilemma which finally led to a change of diagnosis from nephroblastoma to neuroblastoma. This case underlines the importance of gene-expression profiling in the correct diagnosis of childhood neoplasms with atypical presentation to ensure that adequate treatment regimens can be applied.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-017-2724-4) contains supplementary material, which is available to authorized users.

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Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients

Cited by 7 publications

References 41 publications

Systematic review of the immunological landscape of Wilms tumors

Systematic review of the immunological landscape of Wilms tumors

Myasthenia Gravis: Analysis of Serum Autoantibody Reactivities to 1827 Potential Human Autoantigens by Protein Macroarrays

Case report: value of gene expression profiling in the diagnosis of atypical neuroblastoma

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