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Sahajpreet Singh, Phillip Stafford, Karen A Schlauch, Richard R Tillett, Martin Gollery, Stephen Albert Johnston, Svetlana F Khaiboullina, Kenny L De Meirleir, Shanti Rawat, Tatjana Mijatovic, Krishnamurthy Subramanian, András Palotás, Vincent C Lombardi
Myalgic encephalomyelitis (ME) is a complex, heterogeneous illness of unknown etiology. The search for biomarkers that can delineate cases from controls is one of the most active areas of ME research; however, little progress has been made in achieving this goal. In contrast to identifying biomarkers that are directly involved in the pathological process, an immunosignature identifies antibodies raised to proteins expressed during, and potentially involved in, the pathological process. Although these proteins might be unknown, it is possible to detect antibodies that react to these proteins using random peptide arrays...
December 15, 2016: Molecular Neurobiology
Igor B Kuznetsov
Immunosignaturing is an emerging experimental technique that uses random sequence peptide microarrays to detect antibodies produced by the immune system in response to a particular disease. Two important questions regarding immunosignaturing are "Do microarray peptides that exhibit a strong affinity to a given type of antibodies share common sequence properties?" and "If so, what are those properties?" In this work, three statistical tests designed to detect non-random patterns in the amino acid makeup of a group of microarray peptides are presented...
May 2016: Biopolymers
Phillip Stafford, Daniel Wrapp, Stephen Albert Johnston
The humoral immune system is network of biological molecules designed to maintain a healthy homeostatic equilibrium. Because antibodies are an abundant and highly specific effector of immunological action, they are also an important reservoir of previous host exposures. Antibodies may play a major role in early detection of host challenge. Unfortunately, few practical methods exist for interpreting the information stored in antibody variable regions. Immunosignatures use a microarray of thousands of random sequence peptides to interrogate antibodies in a broad and unbiased fashion...
May 2016: Molecular & Cellular Proteomics: MCP
Yariv Wine, Andrew P Horton, Gregory C Ippolito, George Georgiou
The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up unprecedented opportunities to transform our understanding of numerous key questions in adaptive humoral immunity, including the nature and dynamics of serological memory, the role of polyspecific antibodies in health and disease and how protective responses to infections or vaccine challenge arise...
August 2015: Current Opinion in Immunology
Andrei I Chapoval, J Bart Legutki, Philip Stafford, Andrey V Trebukhov, Stephen A Johnston, Yakov N Shoikhet, Alexander F Lazarev
Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Brian O'Donnell, Alexander Maurer, Antonia Papandreou-Suppappola, Phillip Stafford
One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body's immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are one such assay: they provide a map of antibody interactions with random-sequence peptides. They enable detection of disease-specific patterns using classic train/test methods...
2015: Cancer Informatics
Krupa Arun Navalkar, Stephan Albert Johnston, Phillip Stafford
Diagnostics using peptide ligands have been available for decades. However, their adoption in diagnostics has been limited, not because of poor sensitivity but in many cases due to diminished specificity. Numerous reports suggest that protein-based rather than peptide-based disease detection is more specific. We examined two different approaches to peptide-based diagnostics using Coccidioides (aka Valley Fever) as the disease model. Although the pathogen was discovered more than a century ago, a highly sensitive diagnostic remains unavailable...
February 2015: Journal of Immunological Methods
Stephen Albert Johnston, Douglas H Thamm, Joseph Barten Legutki
BACKGROUND: Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the immunosignature as a diagnostic for spontaneous canine lymphoma at both at initial diagnosis and evaluating the disease free interval following treatment. METHODS: Sera from dogs with confirmed lymphoma (B cell n = 38, T cell n = 11) and clinically normal dogs (n = 39) were analyzed...
2014: BMC Cancer
Joseph Barten Legutki, Zhan-Gong Zhao, Matt Greving, Neal Woodbury, Stephen Albert Johnston, Phillip Stafford
There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed microarrays are not scalable. Here we demonstrate a platform based on fabricating microarrays (~10 M peptides per slide, 330,000 peptides per assay) on silicon wafers using equipment common to semiconductor manufacturing...
September 3, 2014: Nature Communications
Phillip Stafford, Zbigniew Cichacz, Neal W Woodbury, Stephen Albert Johnston
Although the search for disease biomarkers continues, the clinical return has thus far been disappointing. The complexity of the body's response to disease makes it difficult to represent this response with only a few biomarkers, particularly when many are present at low levels. An alternative to the typical reductionist biomarker paradigm is an assay we call an "immunosignature." This approach leverages the response of antibodies to disease-related changes, as well as the inherent signal amplification associated with antigen-stimulated B-cell proliferation...
July 29, 2014: Proceedings of the National Academy of Sciences of the United States of America
Krupa Arun Navalkar, Stephen Albert Johnston, Neal Woodbury, John N Galgiani, D Mitchell Magee, Zbigniew Chicacz, Phillip Stafford
Valley fever (VF) is difficult to diagnose, partly because the symptoms of VF are confounded with those of other community-acquired pneumonias. Confirmatory diagnostics detect IgM and IgG antibodies against coccidioidal antigens via immunodiffusion (ID). The false-negative rate can be as high as 50% to 70%, with 5% of symptomatic patients never showing detectable antibody levels. In this study, we tested whether the immunosignature diagnostic can resolve VF false negatives. An immunosignature is the pattern of antibody binding to random-sequence peptides on a peptide microarray...
August 2014: Clinical and Vaccine Immunology: CVI
Stephanie Williams, Phillip Stafford, Steven A Hoffman
BACKGROUND: An accurate method that can diagnose and predict lupus and its neuropsychiatric manifestations is essential since currently there are no reliable methods. Autoantibodies to a varied panel of antigens in the body are characteristic of lupus. In this study we investigated whether serum autoantibody binding patterns on random-sequence peptide microarrays (immunosignaturing) can be used for diagnosing and predicting the onset of lupus and its central nervous system (CNS) manifestations...
2014: BMC Immunology
Cecilia S Lindestam Arlehamn, Alessandro Sette
We have recently described the first true genome-wide screen for CD4(+) T-cell reactivity directed against Mycobacterium tuberculosis (MTB) in latent TB-infected individuals. The approach relied on predictions of HLA-binding capacity for a panel of DR, DP, and DQ alleles representative of those most commonly expressed in the general population, coupled with high throughput ELISPOT assays. The results identified hundreds of novel epitopes and antigens, and documented the novel observation that T cells in latent MTB infection are confined to the CXCR3(+)CCR6(+) phenotype and largely directed against three antigenic "islands" within the MTB genome...
2014: Frontiers in Immunology
Luhui Shen, Debra Tumbula Hansen, Stephen Albert Johnston, Joseph Barten Legutki
The exciting prospect of developing a universal prophylactic cancer vaccine now seems more possible due to advances in technology and basic knowledge. However, the problem of testing the efficacy of such a vaccine in a clinical trial seems daunting. The low incidence and long lead-time to diagnosis of cancer would make a standard clinical trial long and expensive. Recently, we demonstrated that the immunosignatures diagnostic technology could be useful in evaluating vaccines. The technology is based on profiling the antibody diversity in an individual on a peptide chip platform...
May 2014: Expert Review of Vaccines
Joseph Barten Legutki, Stephen Albert Johnston
The development of new vaccines would be greatly facilitated by having effective methods to predict vaccine performance. Such methods could also be helpful in monitoring individual vaccine responses to existing vaccines. We have developed "immunosignaturing" as a simple, comprehensive, chip-based method to display the antibody diversity in an individual on peptide arrays. Here we examined whether this technology could be used to develop correlates for predicting vaccine effectiveness. By using a mouse influenza infection, we show that the immunosignaturing of a natural infection can be used to discriminate a protective from nonprotective vaccine...
November 12, 2013: Proceedings of the National Academy of Sciences of the United States of America
Kathryn F Sykes, Joseph B Legutki, Phillip Stafford
Health is a complex interaction between metabolism, physiology, and immunity. Although it is difficult to define quantitatively, the activity of the humoral immune system provides a reasonable proxy for changes in health. Immunosignaturing is a microarray-based technology that quantitates the dynamics of circulating antibodies. Recent advancements in the field warrant a review of the technology. Here, we provide an introduction to the technique, evaluate the current progress, contrast similar technologies, and suggest applications that immunosignaturing could facilitate...
January 2013: Trends in Biotechnology
Lucas Restrepo, Phillip Stafford, Stephen Albert Johnston
A practical diagnostic test is needed for early Alzheimer's disease (AD) detection. Immunosignaturing, a technology that employs antibody binding to a random-sequence peptide microarray, generates profiles that distinguish transgenic mice engineered with familial AD mutations (APPswe/PSEN1-dE9) from non-transgenic littermates. It can also detect an AD-like signature in humans. Here, we assess the changes in the immunosignature at different time points of the disease in mice and humans. We also evaluate the accuracy of the late-stage signature as a test to discriminate between young mice with familial AD mutations from non-transgenic littermates...
January 15, 2013: Journal of Neuroimmunology
Alexa K Hughes, Zbigniew Cichacz, Adrienne Scheck, Stephen W Coons, Stephen Albert Johnston, Phillip Stafford
Immunosignaturing shows promise as a general approach to diagnosis. It has been shown to detect immunological signs of infection early during the course of disease and to distinguish Alzheimer's disease from healthy controls. Here we test whether immunosignatures correspond to clinical classifications of disease using samples from people with brain tumors. Blood samples from patients undergoing craniotomies for therapeutically naïve brain tumors with diagnoses of astrocytoma (23 samples), Glioblastoma multiforme (22 samples), mixed oligodendroglioma/astrocytoma (16 samples), oligodendroglioma (18 samples), and 34 otherwise healthy controls were tested by immunosignature...
2012: PloS One
Muskan Kukreja, Stephen Albert Johnston, Phillip Stafford
BACKGROUND: High-throughput technologies such as DNA, RNA, protein, antibody and peptide microarrays are often used to examine differences across drug treatments, diseases, transgenic animals, and others. Typically one trains a classification system by gathering large amounts of probe-level data, selecting informative features, and classifies test samples using a small number of features. As new microarrays are invented, classification systems that worked well for other array types may not be ideal...
2012: BMC Bioinformatics
Phillip Stafford, Rebecca Halperin, Joseph Bart Legutki, Dewey Mitchell Magee, John Galgiani, Stephen Albert Johnston
Identifying new, effective biomarkers for diseases is proving to be a challenging problem. We have proposed that antibodies may offer a solution to this problem. The physical features and abundance of antibodies make them ideal biomarkers. Additionally, antibodies are often elicited early in the ontogeny of different chronic and infectious diseases. We previously reported that antibodies from patients with infectious disease and separately those with Alzheimer's disease display a characteristic and reproducible "immunosignature" on a microarray of 10,000 random sequence peptides...
April 2012: Molecular & Cellular Proteomics: MCP
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