Onconeural Versus Paraneoplastic Antigens?

Eichmüller, Stefan B.; Bazhin, Alexandr V.

doi:10.2174/092986707782023668

Cited by 12 publications

(7 citation statements)

References 70 publications

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“…The antibodies are often present in sera from patients suffering from neurological PNS [15], [21], [22]. Scientific evidence has shown that anti-Ma2 positive sera sometimes are associated with tumor diagnosis [15], [16], [23], [24].…”

Section: Introductionmentioning

confidence: 99%

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

et al. 2010

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BackgroundSmall intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs.Methodology/Principal FindingsA novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples.ConclusionHere we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

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Section: Introductionmentioning

confidence: 99%

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

et al. 2010

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“…Most paraneoplastic syndromes are considered to be autoimmune-mediated. The autoimmune responseresultsinthegenerationofspecificcytotoxicT-cells and autoantibodies that react with neural proteins and the causal tumor, so-called onconeural antigens [7,8]. Typical MRI findings of PLE include unilateral or bilateral mesial temporal lobe abnormalities that are best seen on T2-weighted images, but in 20% of the patients, as in our case, MRIfailstoshowchangeswithinthelimbicsystem [9].…”

Section: Discussionmentioning

confidence: 84%

Paraneoplastic Limbic Encephalitis in a Patient with Extragonadal Choriocarcinoma – Significance of Onconeural Antibodies

Szkandera¹,

Ploner²,

Bauernhofer³

et al. 2010

Onkologie

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Background: Paraneoplastic limbic or brainstem encephalitis is considered to be an autoimmune-mediated disorder of the nervous system associated with different types of cancer including germ cell tumors. Case Report: We report on a 31-year-old patient presenting with eye motility dysfunction, dysarthrophonia, lethargy, depression, slow mentation, disorientation, dysgraphia, and retarded motion sequence. Neurologic tests, brain imaging, and blood chemistry tests failed to determine the cause of the symptoms. Further examinations including ultrasound of the abdomen led to the detection of a retroperitoneal mass. The biopsy of this mass showed fractions of a choriocarcinoma. The patient underwent curative chemotherapy, but although the cancer therapy was successful, the neurologic disorders did not improve. Concurrent examination for anti-Ma2 antibodies in the serum was positive and confirmed the paraneoplastic origin of these symptoms. Conclusions: Patients with symptoms of limbic or brainstem encephalitis, especially young men, should be tested for anti-Ma2 antibodies in the serum to elucidate their origin. The detection of these antibodies supports the diagnosis of a paraneoplastic syndrome, and may lead to the earlier identification of an otherwise hidden extragonadal germ cell tumor.

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“…2 To prove this hypothesis, we isolated splenocytes (as a source of both T and B cells) and serum (as a source of immunoglobulins) from tumor-bearing mice and adoptively transferred them into healthy mice. One quarter of the recipients showed retinal degenerations.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐retina antigens as potential paraneoplastic antigens in melanoma‐associated retinopathy

Bazhin

Dalke

Willner

et al. 2008

Intl Journal of Cancer

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Melanoma-associated retinopathy is a rare paraneoplastic neurological syndrome characterized by retinopathy in melanoma patients. The main photoreceptor proteins have been found to be expressed as cancer-retina antigens in melanoma. Here we present evidence that these can function as paraneoplastic antigens in melanoma-associated retinopathy. Sera and one tumor cell line of such patients were studied and ret-transgenic mice spontaneously developing melanoma were used as a murine model for melanoma-associated retinopathy. Splenocytes and sera were used for adoptive transfer from tumor-bearing or control mice to wildtype mice. Retinopathy was investigated in mice by funduscopy, electroretinography and eye histology. Expression of photoreceptor proteins and autoantibodies against arrestin and transducin were detected in melanoma-associated retinopathy patients. In tumor-bearing ret-transgenic mice, retinopathy was frequently (13/ 15) detected by electroretinogram and eye histology. These pathological changes were manifested in degenerations of photoreceptors, bipolar cells and pigment epithelium as well as retinal detachment. Mostly these defects were combined. Cancer-retina antigens were expressed in tumors of these mice, and autoantibodies against arrestin were revealed in some of their sera. Adoptive transfer of splenocytes and sera from tumor-bearing into wildtype mice led to the induction of retinopathy in 4/16 animals. We suggest that melanoma-associated retinopathy can be mediated by humoral and/or cellular immune responses against a number of cancer-retina antigens which may function as paraneoplastic antigens in melanoma-associated retinopathy. '

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Onconeural Versus Paraneoplastic Antigens?

Cited by 12 publications

References 70 publications

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

Paraneoplastic Limbic Encephalitis in a Patient with Extragonadal Choriocarcinoma – Significance of Onconeural Antibodies

Cancer‐retina antigens as potential paraneoplastic antigens in melanoma‐associated retinopathy

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