scholarly journals Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Aristo Vojdani ◽  
Elroy Vojdani ◽  
Datis Kharrazian
Keyword(s):  
Monoclonal Antibodies ◽  
Autoimmune Diseases ◽  
Human Tissue ◽  
Molecular Mimicry ◽  
Disease Process ◽  
Cross Reactivity ◽  
Immune Reactivity ◽  
Human Tissues ◽  
Human Monoclonal Antibodies ◽  
Tissue Antigens

We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.

scholarly journals Reaction of Lectin-Specific Antibody with Human Tissue: Possible Contributions to Autoimmunity

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Aristo Vojdani ◽  
Daniel Afar ◽  
Elroy Vojdani
Keyword(s):  
Specific Antibody ◽  
Human Tissue ◽  
Immunoglobulin E ◽  
Molecular Mimicry ◽  
Cross Reactivity ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Carbohydrate Binding ◽  
Direct Reaction ◽  
Tissue Antigens

The aim of this study was to examine the direct reaction of specific lectin/agglutinin antibodies to different tissue antigens to confirm the theory that reactivity between them may contribute to autoimmunities. Lectins are carbohydrate-binding proteins found in nearly all fruits and vegetables. Undigested lectins can penetrate the gut barriers, provoking an immune response that results in the production of antibodies against them. Using an enzyme-linked immunosorbent assay, we reacted lectin-specific antibodies with 62 different tissue antigens. Wheat germ agglutinin-specific antibody was the most reactive with the tissue antigens (37 tissues out of 62), followed by red kidney bean phytohemagglutinin-specific antibody (20), soybean agglutinin-specific antibody (20), and peanut agglutinin-specific antibody (15). This reaction between anti-lectin antibodies and many human tissue antigens may be due to possible molecular mimicry and cross-reactivity. After our results confirmed that anti-lectin antibodies bind with human tissues, we wanted to determine the prevalence of these antibodies in the blood of 500 nominally healthy donors. The percentage elevation of antibodies against different lectins ranged from 12 to 16% (Immunoglobulin G), 9.7-14.7% (Immunoglobulin A), 12-18% (Immunoglobulin M), and 7.8-14.6% (Immunoglobulin E). Serial dilutions and inhibition study confirmed that these reactions were specific. Finally, we tested the lectin-specific antibody level in sera both negative and positive for RF and ANA and found that IgM anti-lectin antibody levels were highly correlated with RF but not with ANA level. The reaction of anti-lectin antibodies with human tissue components and their detection in RF-positive samples may describe mechanisms by which the production of antibodies against undigested lectins may contribute to the pathogenesis of some autoimmune diseases.

scholarly journals Cross—reactivity of antibodies against microbial proteins to human tissues as basis of Crohn’s disease and other autoimmune diseases

2017 ◽  
Author(s):  
Peilin Zhang ◽  
Lawrence M. Minardi ◽  
J. Todd Kuenstner ◽  
Stephen M. Zekan ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Autoimmune Disease ◽  
Crohn's Disease ◽  
Autoimmune Diseases ◽  
Human Tissue ◽  
Mycobacterium Avium Subspecies Paratuberculosis ◽  
Elongation Factor ◽  
Cross Reactivity ◽  
Human Tissues ◽  
Normal Human

AbstractBackgroundAutoimmune disease is generally a systemic inflammatory response with production of autoantibodies. In this study, we investigated the anti-microbial antibodies in circulation in cases of Crohn’s disease (CD), Sjogren’s syndrome (SS) and other autoimmune disease and their roles in the pathogenesis of these autoimmune diseases.Material and methodsWestern blot was used to determine the reactivity of human plasmas from patients with CD and SS as the primary antibodies against the whole microbial extracts. The microbial proteins reactive to patients’ plasma were further identified and the modified sandwich ELISA assays were used to determine the blood levels of antibodies against these microbial proteins in patients with CD and SS. Antibodies against the microbial proteins are used for immunohistochemical staining of normal human tissue.ResultsA group of 7 microbial proteins was identified reactive to the plasmas of patients with CD and SS including DNA-directed RNA polymerase B (RPOB), and elongation factor G (EF-G) fromStaphylococcus aureusandStaphylococcus pseudintermedius(S. aureusandS. pseudintermedius), ATP synthase alpha (ATP5a) and heat shock protein 65 (Hsp65) fromMycobacterium avium subspecies paratuberculosis(MAP), elongation factor Tu (EF-Tu) and outer membrane porin C (ompC) fromEscherichia Coli(E. coli). Anti-microbial antibodies can cross-react to normal human tissues. The levels of antibodies against the microbial proteins are significantly elevated in the patients with CD and SS.ConclusionThe levels of antibodies against the microbial proteins are significantly elevated in CD and SS. The cross-reactivity of the anti-microbial antibodies to human tissue provides a new mechanism of pathogenesis of autoimmune diseases such as CD and SS.

scholarly journals Rheumatoid Arthritis is an Autoimmune Disease Triggered byProteusUrinary Tract Infection

2006 ◽  
Vol 13 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Alan Ebringer ◽  
Taha Rashid
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mimicry ◽  
Disease Process ◽  
Cross Reactivity ◽  
Evidence Based ◽  
High Intake ◽  
Tissue Antigens ◽  
Vegetarian Diets ◽  
Tract Infections ◽  
Different Parts

Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age.Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists betweenProteus mirabilismicrobes and RA. We propose that sub-clinicalProteusurinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies.Patients with RA especially during the early stages of the disease could benefit fromProteusanti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.

Generation of Human Monoclonal Anti-idiotypic Antibodies with Specificity to the Murine Monoclonal Anti-CA 125 Antibody B43.13

1996 ◽  
Vol 11 (4) ◽  
pp. 211-215
Author(s):  
J.B. Oltrogge ◽  
B. Donnerstag ◽  
R.P. Baum ◽  
A.A. Noujaim ◽  
L. Träger
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Peripheral Blood Lymphocytes ◽  
Cross Reactivity ◽  
Tumor Burden ◽  
Ca 125 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Monoclonal Antibodies ◽  
Ebv Transformation

Two human monoclonal antibodies, HID-7E7 and ROB-6F2, were produced by EBV transformation of peripheral blood lymphocytes (PBL). PBL were obtained from a patient with ovarian cancer who had been exposed several times to a Tc-99m labeled murine monoclonal anti-CA 125 antibody (B43.13, Biomira, Edmonton) for immunoscintigraphy. The HID-7E7 and ROB-6F2 producing B-cells were cloned with a limiting dilution technique and have shown stable immunoglobulin secretion within a period of three years. The human monoclonal antibodies HID-7E7 and ROB-6F2 are of the IgG isotype, and bind with significant affinity to the murine monoclonal antibody B43.13, which was used for immunoscintigraphy. Binding affinity of ROB-6F2 to other murine antibodies could not be detected. Cross reactivity of HID-7E7 to a murine anti-CEA monoclonal antibody was observed. In order to verify the anti-idiotypic character of the generated human antibodies, the ability of HID-7E7 and ROB-6F2, respectively, to inhibit the formation of the CA125/B43.13 complex is demonstrated via an enzyme-linked immunosorbent assay. These human anti-idiotypic antibodies are possible candidates for immunotherapy of ovarian cancer in patients with a small tumor burden following surgery and/or chemotherapy.

Evaluation of procedures for the fixation and processing of human tissue for immunohistochemical analysis of human monoclonal antibodies

1991 ◽  
Vol 2 (3) ◽  
pp. 135-141 ◽  
Author(s):  
Henrik Ditzel ◽  
Karin Erb ◽  
Per Borup-Christensen ◽  
Bjarne Nielsen ◽  
Jens Chr. Jensenius
Keyword(s):  
Monoclonal Antibodies ◽  
Human Tissue ◽  
Immunohistochemical Analysis ◽  
Human Monoclonal Antibodies

Molecular Mimicry Accompanying HIV-1 Infection: Human Monoclonal Antibodies That Bind to gp41 and to Astrocytes

1993 ◽  
Vol 9 (10) ◽  
pp. 939-944 ◽  
Author(s):  
MICHAEL EDDLESTON ◽  
JUAN CARLOS DE LA TORRE ◽  
JIAN-YIN XU ◽  
NICKOLAS DORFMAN ◽  
ABNER NOTKINS ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mimicry ◽  
Human Monoclonal Antibodies ◽  
Hiv 1

scholarly journals Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach

2020 ◽  
Author(s):  
Hyunsu An ◽  
Jihwan Park
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Web Application ◽  
Molecular Mimicry ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Cross Reactivity ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Human Proteins

ABSTRACTCurrently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application “Molecular Mimicry Map (3M) of SARS-CoV-2” (available at https://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.

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