Post-treatment Lyme disease symptoms (PTLDS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have several clinical features in common, including fatigue, musculoskeletal pain, and cognitive difficulties (Gaudino et al., 1997). Immunologic mechanisms have been suspected to play a role in both PTLDS and ME/CFS. However, biomarkers for the two conditions are currently lacking, creating a barrier to better understand them. In a previous study published in BBI, we developed a semi-quantitative immunoblot assay to compare antibody reactivity to neural antigens in a group of PTLDS patients and controls (Chandra et al., 2010). Inclusion/exclusion criteria were previously described (Chandra et al., 2010). We found a significantly increased level and frequency of IgG anti-neural antibody reactivity in the PTLDS patients (41 of 83; 49.4%) both in comparison to patients who had been treated for Lyme disease previously but did not have residual symptoms (5 of 27; 18.5%) and to healthy controls who never had Lyme disease (3 of 20; 15.0%) (p<0.01 for both comparisons). The anti-neural antibody response in the patients with PTLDS was independent of serologic positivity for antibodies to Borrelia burgdorferi (the etiologic agent of Lyme disease).
Using the same methodology in a new analysis, we screened plasma samples from 51 ME/CFS patients (36 female; mean [SD] age, 51.2 [11.7] years) and 53 age- and gender-matched healthy controls (40 female; mean age, 50.0 [13.6] years), provided by the SolveCFS BioBank (Irlbeck et al., 2014). This study was approved by the Institutional Review Board of Columbia University Medical Center. The ME/CFS and control sample sizes in this study provided greater than 90% power, with α<0.05, to detect the same frequencies of antibody reactivity previously observed in the PTLDS patients and associated controls (Chandra et al., 2010). ME/CFS patients met the Fukuda or the Canadian criteria for this condition (Carruthers, 2007; Fukuda et al., 1994) and lacked histories suggestive of Lyme disease. Screening questionnaires were used to evaluate the general health of the unaffected controls and to confirm that that they did not meet ME/CFS case definition criteria. In contrast to the findings of our prior study on PTLDS patients (Chandra et al., 2010), we found no significant difference in the prevalence of anti-neural antibody reactivity between ME/CFS patients (4 of 51; 7.8%) and healthy controls (7 of 53; 13.2%) (p=0.5).
Although often detectable (Chandra et al., 2010), it is unclear whether the presence of anti-neural antibodies has a role in the pathogenesis of certain PTLDS manifestations. If these antibodies do play a role, it would appear that the cause of the somewhat similar symptoms in ME/CFS is different. A potential limitation of the methodology employed in this and in our prior study (Chandra et al., 2010) is that it primarily detects reactivity to prominently expressed neural proteins and can miss reactivity to some minor proteins or non-protein antigens. Further inquiry into B cell activation mechanisms and autoantibody response may be useful to gaining a better understanding of differences between PTLDS and ME/CFS, and might provide potential markers for the identification of disease subsets.
Acknowledgments
Funding/support: Research reported here was supported by grants from the Solve ME/CFS Initiative, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R56AI093763 and R21AI071180), and the Lyme Research Alliance. The funding organizations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Disclaimer and potential conflicts of interest: Dr. Alaedini reports receiving grants from the National Institutes of Health and the Lyme Research Alliance for research related to Lyme disease, and from the Solve ME/CFS Initiative for research related to ME/CFS. Dr. Wormser reports receiving research grants from Immunetics, Inc., Rarecyte, Inc., Institute for Systems Biology, and bioMérieux SA. He owns equity in Abbott; has been an expert witness in malpractice cases involving Lyme disease and babesiosis; is an unpaid board member of the American Lyme Disease Foundation; and was a consultant to Baxter for Lyme disease vaccine development.
References
- Carruthers BM. Definitions and aetiology of myalgic encephalomyelitis: how the Canadian consensus clinical definition of myalgic encephalomyelitis works. J Clin Pathol. 2007;60:117–119. doi: 10.1136/jcp.2006.042754. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chandra A, Wormser GP, Klempner MS, Trevino RP, Crow MK, Latov N, Alaedini A. Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms. Brain Behav Immun. 2010;6:1018–1024. doi: 10.1016/j.bbi.2010.03.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994;121:953–959. doi: 10.7326/0003-4819-121-12-199412150-00009. [DOI] [PubMed] [Google Scholar]
- Gaudino EA, Coyle PK, Krupp LB. Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences. Arch Neurol. 1997;54:1372–1376. doi: 10.1001/archneur.1997.00550230045015. [DOI] [PubMed] [Google Scholar]
- Irlbeck DM, Vernon SD, McCleary KK, Bateman L, Klimas NG, Lapp CW, Peterson DL, Brown JR, Remlinger KS, Wilfret DA, Gerondelis P. No association found between the detection of either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BioBank. BMC Res Notes. 2014;7:461. doi: 10.1186/1756-0500-7-461. [DOI] [PMC free article] [PubMed] [Google Scholar]