TY - JOUR
T1 - Humoral immunity profiling of subjects with myalgic encephalomyelitis using a random peptide microarray differentiates cases from controls with high specificity and sensitivity
AU - Singh, Sahajpreet
AU - Stafford, Phillip
AU - Schlauch, Karen A.
AU - Tillett, Richard R.
AU - Gollery, Martin
AU - Johnston, Stephen
AU - Khaiboullina, Svetlana F.
AU - De Meirleir, Kenny L.
AU - Rawat, Shanti
AU - Mijatovic, Tatjana
AU - Subramanian, Krishnamurthy
AU - Palotás, András
AU - Lombardi, Vincent C.
N1 - Funding Information:
Acknowledgements These studies were supported by awards from the National Institutes of Health (R01AI078234) and the National Institute of General Medical Sciences (GM103440), from the National Institutes of Health, and from funds donated by the ME/CFS community. We are additionally grateful to all our study subjects, whose selfless participation made this research possible. Compliance with Ethical Standards Informed consent was obtained from each participant according to a human subjects protocol approved by the University of Nevada Biomedical Institutional Review Board (protocol B12-031).
Publisher Copyright:
© The Author(s) 2016.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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. In the present study, we probe a custom 125,000 random 12-mer peptide microarray with sera from 21 ME cases and 21 controls from the USA and Europe and used these data to develop a diagnostic signature. We further used these peptide sequences to potentially uncover the naturally occurring candidate antigens to which these antibodies may specifically react with in vivo. Our analysis revealed a subset of 25 peptides that distinguished cases and controls with high specificity and sensitivity. Additionally, Basic Local Alignment Search Tool (BLAST) searches suggest that these peptides primarily represent human selfantigens and endogenous retroviral sequences and, to a minor extent, viral and bacterial pathogens.
AB - 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. In the present study, we probe a custom 125,000 random 12-mer peptide microarray with sera from 21 ME cases and 21 controls from the USA and Europe and used these data to develop a diagnostic signature. We further used these peptide sequences to potentially uncover the naturally occurring candidate antigens to which these antibodies may specifically react with in vivo. Our analysis revealed a subset of 25 peptides that distinguished cases and controls with high specificity and sensitivity. Additionally, Basic Local Alignment Search Tool (BLAST) searches suggest that these peptides primarily represent human selfantigens and endogenous retroviral sequences and, to a minor extent, viral and bacterial pathogens.
KW - Antibody
KW - Chronic fatigue syndrome
KW - Immunosignature
KW - Myalgic encephalomyelitis
KW - Peptide array
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U2 - 10.1007/s12035-016-0334-0
DO - 10.1007/s12035-016-0334-0
M3 - Article
C2 - 27981498
AN - SCOPUS:85050508758
SN - 0893-7648
VL - 55
SP - 633
EP - 641
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 1
ER -