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Cytosolic 5′-nucleotidase IA (cN-IA) plays a central role in the regulation of the purine nucleotide pool in skeletal muscle, preferentially converting adenosine monophosphate to adenosine. cN-IA can act as an autoantigen in muscle diseases, including the paraneoplastic syndrome related to breast cancer (BC). As a result of myocyte damage, released cN-IA protein may trigger the production of anti-cN-IA antibodies (anti-NT5C1A). This work aimed to develop an effective method to measure cN-IA activity in the serum and analyze it in BC patients. Our study demonstrated that serum cN-IA activity was decreased in BC patients and we assumed it is due to the presence of specific autoantibodies. We found correlations between cN-IA activity and parameters of inflammatory muscle damage. Thus, cN-IA is worth further attention to clarify its usefulness as a biomarker of BC-associated polymyositis. [ABSTRACT FROM AUTHOR]

Discovery and characterization of serologic biomarkers has revolutionized the diagnostic framework of systemic and paraneoplastic autoimmune neuro-ophthalmic diseases. Expanding recognition of the multiple ocular and visual manifestations of these conditions highlights the important role of the referring provider in identifying potential cases. Increasing ease of access to serologic testing also enables these practitioners to initiate the diagnostic work-up in suspected cases. We aimed to provide an update on the current knowledge surrounding and use of relevant autoimmune biomarkers by correlating specific clinical neuro-ophthalmic manifestations with autoantibody biomarkers. The utility of select biomarkers for myasthenia gravis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein-IgGassociated disorder, opsoclonus-myoclonus syndrome, anti-collapsin-response mediator protein-5 optic neuropathy, and glial fibrillary acidic protein-IgG-associated disease are discussed with particular focus on the clinical contexts in which to consider testing. [ABSTRACT FROM AUTHOR]

Purpose: To describe outcomes of combined rituximab and bortezomib treatment for non-paraneoplastic autoimmune retinopathy.Case: A 37-year-old female developed photopsias and reduced vision. Electroretinography, optical coherence tomography, and positive serum anti-retinal antibodies were consistent with autoimmune retinopathy. A negative malignancy work-up specified her non-paraneoplastic presentation. Given absence of response to periocular steroids, azathioprine, and methotrexate, a combination of rituximab and bortezomib was initiated as fifth-line therapy.Results: There was no significant improvement in the patient's symptoms or visual function following treatment. The full field electroretinogram amplitudes were reduced with progressive outer retinal degeneration evident on optical coherence tomography. Post-treatment anti-retinal antibody testing demonstrated the persistence of antibodies and revealed additional antibodies not previously detected.Conclusion: Combined rituximab and bortezomib treatment did not result in significant clinical improvement and there was evidence of disease progression. Further prospective studies are required to assess the efficacy of immunotherapy in patients with autoimmune retinopathy. [ABSTRACT FROM AUTHOR]

In 10-30% of MDS and CMML cases, autoimmune or auto-inflammatory disorders (AID) could occur concomitantly, before or after the MDS/CMML diagnosis [[1]]. Our purpose was to evaluate the frequencies of autoantibodies in MDS/CMML patients without clinical AID in comparison to MDS/CMML patients with various AID and to healthy controls. The MDS/CMML patients with AID were younger (75 (16-90) years vs. 77 (37-94) than MDS/CMML patients without AID ( I p i <.001) and had higher levels of C-reactive protein (41 (0-210) mg/L vs. 4 (1-39); I p i <.00001). [Extracted from the article]

Background: Experts in the autoimmune paraneoplastic field recommend autoantibody testing as “panels” to improve the poor sensitivity of individual autoantibodies in detecting paraneoplastic neurological syndromes (PNS). The sensitivity of those panels was not reported to date in a fashion devoid of incorporation bias. We aimed to assess the collective sensitivity and specificity of one of the commonly used panels in detecting PNS.Methods: A single-centered retrospective cohort of all patients tested for paraneoplastic evaluation panel (PAVAL; test ID: 83380) over one year for the suspicion of PNS. Case adjudication was based on newly proposed diagnostic criteria in line with previously published literature, but modified to exclude serological status to avoid incorporation bias. Measures of diagnostic accuracy were subsequently calculated. Cases that failed to show association with malignancy within the follow-up time studied, reflecting a possibly pure autoimmune process was considered paraneoplastic-like syndromes.Results: Out of 321 patients tested, 51 patients tested positive. Thirty-two patients met diagnostic criteria for paraneoplastic/paraneoplastic-like syndromes. The calculated collective sensitivity was 34% (95% CI: 17–53), specificity was 86% (95% CI: 81–90), Youden's index 0.2 and a positive clinical utility index 0.07 suggesting poor utility for case-detection.Conclusion: This is the first reported diagnostic accuracy measures of paraneoplastic panels without incorporation bias. Despite recommended panel testing to improve detection of PNS, sensitivity remains low with poor utility for case-detection. The high-calculated specificity suggests a possible role in confirming the condition in difficult cases suspicious for PNS, when enough supportive evidence is lacking on ancillary testing. [ABSTRACT FROM PUBLISHER]

A 68-year-old male presented with blurred vision in both eyes. Ophthalmoscopy revealed bilateral prominent disc swelling and vitritis. No systematic neurological symptoms were observed. Magnetic resonance imaging revealed bilateral meningeal enhancement of the optic nerve. Small cell carcinoma was found, and antibodies against collapsing response-mediating protein-5 (CRMP-5) were detected in the serum. Ophthalmological manifestations disappeared during a decrease in tumour size with treatment for the malignancy. This case report describes this rare case of anti-CRMP-5 antibody–positive paraneoplastic perioptic neuritis without neurological symptoms, showing that prompt diagnosis and timely treatment of the underlying tumour are crucial to prevent increased levels of autoantibodies and irreversible damage to the nervous system. [ABSTRACT FROM AUTHOR]

Epilepsy is a common disorder that may be caused by wide ranging etiologies. Historically a significant number of people with epilepsy have idiopathic epilepsy without a definitive etiology. More recently, auto-antibodies have been discovered to be associated with numerous conditions affecting the nervous system, including epilepsy. With this increased understanding of the potential for immune-based etiologies for epilepsy it is important to recognize the associated EEG patterns in such cases. This report presents the EEG findings in epilepsy patients with one or more auto-antibodies. [ABSTRACT FROM AUTHOR]

PURPOSE: Paraneoplastic retinopathies are currently identified and classified according to specific anti-retina antibody reactions. These cancer-induced retinal degenerations can be accompanied by changes in the character of the retinal pigment epithelium (RPE) indicative of additional, and superimposed, pathologic activity. The antibody reactions of 11 paraneoplastic retinopathy patients were evaluated to identify those whose immunologic abnormalities included indications of RPE hypersensitivity. The pathologic significance of this anomaly was evaluated upon viable monolayers of RPE, in the presence and absence of complement. METHODS: Comparisons of antibody reactions were made using: (1) indirect immunohistochemistry on sections of rhesus monkey eyes; (2) Western blot reactions on extracts of rhesus monkey retina and in vitro-propagated rhesus RPE; and (3) an evaluation of antibody influence upon the metabolic activity of viable monolayers of rhesus RPE cells. RESULTS: Indirect immunohistochemistry on sections of monkey eyes identified antibodies reactive with RPE in four of the 11 cancer patients. The same four were found to identify a 57 kd protein component of these cells in Western blot reactions of RPE and to inhibit the metabolic activity of viable RPE cells through actions enhanced by the addition of complement. One subject from the reference comparison control group, a cancer-free patient with age-related macular degeneration, also exhibited comparable antibody activity with RPE. CONCLUSIONS: RPE hypersensitivity can present as a superimposed immunologic complication to the retinal degenerations of paraneoplastic retinopathies and those unrelated to malignancies. When activated, humoral aspects of the immune response are able to impart pathologic effects that inhibit RPE homeostasis and, consequently, the essential supportive functions of these cells. Since this immunologic abnormality is not confined to cancer patients, it should be considered... [ABSTRACT FROM AUTHOR]

Describes autoantibody reactions in different types of paraneoplastic vision loss. Correlation between neoplasm and paraneoplasias; Investigation on the ability of single cultures to incite the production of anti-retinal antibodies in laboratory animals; Detection of cell carcinoma expressing retinal protein.