Epitopes of Microbial and Human Heat Shock Protein 60 and Their Recognition in Myalgic Encephalomyelitis

Abstract

Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM) immune response was studied in 69 ME patients and 76 blood donors (BD) (the Training set) with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?

“…This is pertinent given that HSP production appears to be deficient in CFS patients, and the HSPs produced appear to be dysfunctional, which could potentially provide another mechanism underpinning a prolonged and/or exaggerated immune response to pathogen invasion and other sources of inflammation such as stress, medical comorbidity and lifestyle factors in such patients (Elfaitouri et al 2013; Jammes et al 2005, 2009, 2011, 2012). …”

Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Not Due to Anti-mitochondrial Antibodies

“…Hypothetically, dangerassociated molecular patterns (DAMPs), such as mitochondrial DNA (mtDNA), heat shock proteins (Hsps), and cardiolipins could be released from the mitochondria (41)(42)(43) in ME/CFS and act as autoantigens. We previously found that a subset of ME/CFS patients had higher levels of IgM antibodies against epitopes of both mitochondrial and bacterial Hsp-60 (despite the absence of an infectious pathogen) which potentially may lead to dysfunctional mitochondria (11). Our hypothesis on the presence of autoantibodies against cardiolipin in ME/CFS patients was based on previous publications (ref in Table 1), could not be confirmed here, possible explained by different inclusion and exclusion criteria of patients in previous studies that did not used Canadian criteria, but included leukemia/lymphoma and type 1 diabetes patients.…”

“…Intermediate filaments (8) Phosphatidylserine (4) Phospholipids, gangliosides (5) Mitochondria Heat shock protein 60 (11) Cardiolipin (4,12,13) Neo-antigens Oleic acid (14) Palmitic acid, myristic acid, S-farnesyl-L-cysteine, malondialdehyde, azelaic acid (15) NO-tyrosine (14,15) NO-phenylalanine (14,15) NO-arginine, NO-tryptophan, NO-cysteinyl (14) NO-Bovine serum albumin (16) NO-histidine, NO-creatine, NO-asparagine (15) Other targets dUTPase (17) Endothelial cells, neuronal cells (4) NO-, nitrosylated; dUTPase, deoxyuridine 5 ′ -triphosphate nucleotide hydrolase.…”

High Throughput Multiplex Serological Testing in Microbiology

“…Immunoassay (SMIA) ( Figure 2) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. We have used it for research on diagnosis and seroprevalence.…”