Seroprevalence of anti-microbial antibodies in the normal healthy population with implications in chronic diseases

Zhang, Peilin; Minardi, Lawrence M.; Kuenstner, J. Todd; Zekan, Steve; Kruzelock, Rusty

doi:10.1101/693655

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…In order to address these questions, we surveyed the normal population for seroprevalence of Hsp65 antibody in blood donors of the American Red Cross, and compared the seroprevalence with those of chronic conditions, such as Crohn's disease and Sjogren's syndrome [17]. Our findings are supportive of the view that chronic diseases are infectious diseases in genetically susceptible individuals and the Hsp65 antibodies in circulation represents an abnormal adaptive immune response to antigens of mycobacterial (environmental) origin.…”

Section: Introductionmentioning

confidence: 66%

Serological Testing for Mycobacterial Heat Shock Protein Hsp65 Antibody in Health and Diseases

Zhang¹,

Minardi²,

Kuenstner³

et al. 2019

Microorganisms

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Mycobacterial heat shock protein 65 gene (Hsp65) has been widely used for classification of Mycobacterial species, and detection of Mycobacterial genes by molecular methods and has proven useful in identification of Mycobacterial infection in various clinical conditions. Circulating antibody against Mycobacterial hsp65 has been found in many clinical diseases including autoimmune diseases (Crohn’s disease, lupus erythematosus, multiple sclerosis, diabetes, etc.), atherosclerosis and cancers. The prevalence of anti-Hsp65 antibody in the normal healthy population is unknown. We determined the blood levels of antibody against Mycobacterial hsp65 in the normal population represented by 288 blood donors of the American Red Cross and tested the blood of 109 patients with Crohn’s disease and 28 patients with Sjogren’s syndrome for comparison. The seroprevalence of anti-Hsp65 IgG in the normal population of Red Cross donors was 2.8% (8 of 288 positive). The Hsp65 antibody levels were significantly elevated in patients with Crohn’s disease and Sjogren’s syndrome. The prevalence of Hsp65 antibody in Crohn’s disease patients was 67.9% (74 of 109 patients), and 85.7% for Sjogren’s patients (24 of 28 patients). Our data indicate that anti-Hsp65 antibody is rare in the normal population, but frequent in chronic diseases. The presence of circulating Hsp65 antibody reflects an abnormal immune (adaptive) response to Mycobacterial exposure in patients with chronic diseases, thus differentiating the patients with chronic diseases from those clinical mimics.

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Section: Introductionmentioning

confidence: 66%

Serological Testing for Mycobacterial Heat Shock Protein Hsp65 Antibody in Health and Diseases

Zhang¹,

Minardi²,

Kuenstner³

et al. 2019

Microorganisms

Self Cite

View full text Add to dashboard Cite

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Mining Autoimmune-Disorder-Linked Molecular-Mimicry Candidates in Clostridioides difficile and Prospects of Mimic-Based Vaccine Design: An In Silico Approach

Alshamrani,

Mashraqi,

Alzamami

et al. 2023

Microorganisms

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Molecular mimicry, a phenomenon in which microbial or environmental antigens resemble host antigens, has been proposed as a potential trigger for autoimmune responses. In this study, we employed a bioinformatics approach to investigate the role of molecular mimicry in Clostridioides difficile-caused infections and the induction of autoimmune disorders due to this phenomenon. Comparing proteomes of host and pathogen, we identified 23 proteins that exhibited significant sequence homology and were linked to autoimmune disorders. The disorders included rheumatoid arthritis, psoriasis, Alzheimer’s disease, etc., while infections included viral and bacterial infections like HIV, HCV, and tuberculosis. The structure of the homologous proteins was superposed, and RMSD was calculated to find the maximum deviation, while accounting for rigid and flexible regions. Two sequence mimics (antigenic, non-allergenic, and immunogenic) of ≥10 amino acids from these proteins were used to design a vaccine construct to explore the possibility of eliciting an immune response. Docking analysis of the top vaccine construct C2 showed favorable interactions with HLA and TLR-4 receptor, indicating potential efficacy. The B-cell and T-helper cell activity was also simulated, showing promising results for effective immunization against C. difficile infections. This study highlights the potential of C. difficile to trigger autoimmunity through molecular mimicry and vaccine design based on sequence mimics that trigger a defensive response.

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Molecular Mimicry Mapping in Streptococcus pneumoniae: Cues for Autoimmune Disorders and Implications for Immune Defense Activation

et al. 2023

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Streptococcus pneumoniae contributes to a range of infections, including meningitis, pneumonia, otitis media, and sepsis. Infections by this bacterium have been associated with the phenomenon of molecular mimicry, which, in turn, may contribute to the induction of autoimmunity. In this study, we utilized a bioinformatics approach to investigate the potential for S. pneumoniae to incite autoimmunity via molecular mimicry. We identified 13 S. pneumoniae proteins that have significant sequence similarity to human proteins, with 11 of them linked to autoimmune disorders such as psoriasis, rheumatoid arthritis, and diabetes. Using in silico tools, we predicted the sequence as well as the structural homology among these proteins. Database mining was conducted to establish links between these proteins and autoimmune disorders. The antigenic, non-allergenic, and immunogenic sequence mimics were employed to design and validate an immune response via vaccine construct design. Mimic-based vaccine construct can prove effective for immunization against the S. pneumoniae infections. Immune response simulation and binding affinity was assessed through the docking of construct C8 to human leukocyte antigen (HLA) molecules and TLR4 receptor, with promising results. Additionally, these mimics were mapped as conserved regions on their respective proteins, suggesting their functional importance in S. pneumoniae pathogenesis. This study highlights the potential for S. pneumoniae to trigger autoimmunity via molecular mimicry and the possibility of vaccine design using these mimics for triggering defense response.

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Seroprevalence of anti-microbial antibodies in the normal healthy population with implications in chronic diseases

Cited by 3 publications

References 25 publications

Serological Testing for Mycobacterial Heat Shock Protein Hsp65 Antibody in Health and Diseases

Serological Testing for Mycobacterial Heat Shock Protein Hsp65 Antibody in Health and Diseases

Mining Autoimmune-Disorder-Linked Molecular-Mimicry Candidates in Clostridioides difficile and Prospects of Mimic-Based Vaccine Design: An In Silico Approach

Molecular Mimicry Mapping in Streptococcus pneumoniae: Cues for Autoimmune Disorders and Implications for Immune Defense Activation

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