Guillain-Barre Syndrome (GBS) has been known to be preceded by various infections such as Campylobacter jejuni, cytomegalovirus, and so on. We have experienced a case of GBS after a preceding herpes zoster, which was complicated by GBS, which is rare. Some circumstantial and experimental clues suggest a possible causal relationship between those two. Here we report the case along with a literature review.
Campylobacter jejuni ; Cytomegalovirus ; Guillain-Barre Syndrome ; Herpes Zoster* ; Molecular Mimicry

Autoimmunity associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been well-described as the mechanism of development of thyroid dysfunction following Coronavirus Disease 19 (COVID-19) infection and SARS-CoV-2 vaccination. However, the occurrence of thyroid eye disease (TED) after SARS-CoV-2 vaccination is scarcely described. The postulated mechanisms include immune reactivation, molecular mimicry and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). We report a case of new-onset TED after receiving the SARSCoV- 2 vaccine.
Thyroid eye disease ; SARS-CoV-2 vaccine ; Molecular Mimicry

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, and its pathogenesis is unclear and complicated. Infection and SLE are similar in that they both cause inf lammatory reactions in the immune system; however, one functions to protect the body, whereas the other is activated to damage the body. Infection is known as one of the common trigger factors for SLE; there are a number of reports on infectious agents that provoke autoimmune response. Several viruses, bacteria, and protozoa were revealed to cause immune dysfunction by molecular mimicry, epitope spreading, and bystander activation. In contrast, certain pathogens were revealed to protect from immune dysregulation. Infection can be threatening to patients with SLE who have a compromised immune system, and it is regarded as one of the common causes of mortality in SLE. A clinical distinction between infection and lupus f lare up is required when patients with SLE present fevers. With a close-up assessment of symptoms and physical examination, C-reactive protein and disease activity markers play a major role in differentiating the different disease conditions. Vaccination is necessary because protection against infection is important in patients with SLE.
Autoimmune Diseases ; Autoimmunity ; Bacteria ; C-Reactive Protein ; Fever ; Humans ; Immune System ; Lupus Erythematosus, Systemic* ; Molecular Mimicry ; Mortality ; Physical Examination ; Vaccination

Polymyositis(PM) is one of idiopathic inflammatory myopathy, characterized by proximal muscle weakness, myalgia and muscle enzyme elevation. Currently the main pathogenesis is well documented, the cell-mediated immunity. We experienced a case of polymyositis associated with hepatitis, developed after hepatitis B virus(HBV) infection. This virus-induced autoimmunity seems to result from the cross-reactivity between muscle protein and B-viral antigen, so called antigenic mimicry. This relation of PM and HBV is more significant in Korea because of the epidemicity of HBV infection.
Autoimmunity ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Immunity, Cellular ; Korea ; Molecular Mimicry ; Muscle Proteins ; Muscle Weakness ; Myalgia ; Myositis ; Polymyositis*

The Miller Fisher syndrome (MFS), characterized by ataxia, areflexia, and ophthalmoplegia, is a localized variant of Guillain-Barre syndrome (GBS). Bickerstaff's brainstem encephalitis (BBE) is a related syndrome in which central nervous system abnormalities accompany the classic triad. The discovery of the anti-GQ1b antibody and localization of GQ1b ganglioside in human nervous system enabled us to understand various kinds of symptoms in MFS and related diseases. Molecular mimicry of antigenic epitope from infective organisms such as Campylobacter jejuni with this ganglioside is likely the predominant pathogenic mechanism. This could explain the unusual conditions such as atypical MFS, GBS with ophthalmoplegia and BBE are various manifestations of post-infectious autoimmune neuropathies. Now, we can speculate them as the anti-GQ1b antibody syndrome in according to their immunological profiles. In addition to this, recent new concept of anti-ganglioside complex antibody will lead us to further understanding of these disorders.
Ataxia ; Brain Stem ; Campylobacter jejuni ; Central Nervous System ; Encephalitis ; Gangliosides ; Guillain-Barre Syndrome ; Humans ; Miller Fisher Syndrome ; Molecular Mimicry ; Nervous System ; Ophthalmoplegia

OBJECTIVEThis study was to investigate the molecular biomarkers of apoptosis induced by BH3 mimetic S1 in human primary AML cells.

METHODSMononuclear cells were isolated from 27 newly diagnosed AML samples. Apoptosis was analyzed by flow cytometry. IC(50) value of S1 on these samples was determined by XTT assay. The expression level of BCL-2 family members and phosphorylated BCL-2 were assessed by Western blot with subsequent semi-quantitatively densitometric analysis. XTT assay was performed to determine the cell viability of the combined use of S1 and MEK/ERK inhibitor PD98059. The interactions between BCL-2 and pro-apoptosis proteins were tested by co-immunoprecipitation.

RESULTSThe flow-cytometry detection showed that S1 induced the apoptosis of primary AML cells. Based on the responses, 27 primary samples could be classified into three groups: (1) a sensitive group (12 of 27 cases) with IC(50)<14 µmol/L, (2) an intermediate group (8 of 27 cases) with IC(50) of 14-30 µmol/L and (3) a resistant group (7 of 27 cases) with IC(50)>30 µmol/L. The ratio of pBCL-2/(BCL-2+MCL-1) showed a good linear correlation with the IC(50) values. (R(2) = 0.71, P < 0.0001). PD98059 suppressed BCL-2 phosphorylation. When PD98059 suppressed BCL-2 phosphorylation, the apoptotic rate of drug-resistant cells induced by S1 increased from 9.8% to 64.5% (combination index, CI = 0.4), accompanied by more dissociation of BCL-2 heterodimers.

CONCLUSIONThe combination of S1 with PD98059 decrease pBCL-2 level of AML patients and inhibits of the anti-apoptotic function of BCL-2 through enhancing the dissociation of BCL-2 heterodimers.

Antimetabolites, Antineoplastic ; Apoptosis ; Cell Line, Tumor ; Drug Combinations ; Humans ; Leukemia, Myeloid, Acute ; Molecular Mimicry ; Oxonic Acid ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2 ; Tegafur

Guillain-Barré syndrome (GBS) is a representative form of post-infectious autoimmune neuropathy with heterogenous manifestations. It was originally considered as an ascending demyelinating polyneuropathy in Western countries. However, the discovery of anti-ganglioside antibodies on the basis of molecular mimicry theory could help us better understand various kinds of focal and regional variants as well as axonal type of GBS those were frequently found from Asian countries. Recent development of new techniques about anti-ganglioside complex antibodies is making more detailed descriptions for specific or unusual clinical manifestations. It has been regarded that GBS has good prognosis if treated properly as early as possible, but it still shows high mortality and morbidity rate with frequent long term neurologic and medical complications. Unfortunately, there are only two options for medical treatment, intravenous immunoglobulin and plasmapheresis, for the last 100 years. Several clinical studies on new immunotherapy targeting complement activating system with background of molecular mimicry using animal model are underway. We hope that these new treatments will be helpful for the future patients.
Antibodies ; Asian Continental Ancestry Group ; Axons ; Complement System Proteins ; Gangliosides ; Guillain-Barre Syndrome ; Hope ; Humans ; Immunoglobulins ; Immunotherapy ; Miller Fisher Syndrome ; Models, Animal ; Molecular Mimicry ; Mortality ; Plasmapheresis ; Polyneuropathies ; Prognosis

OBJECTIVETo establish systemic lupus erythematosus (SLE) -like murine model by immunizing BALB/C mice with Sm mimotope.

METHODSSm mimotope was identified by screening a 12-mer random peptide library with monoclonal anti-Smith antibody. Sm mimotope was initially defined with sandwich ELISA, DNA sequencing, and deduced amino acid sequence; and BALB/C mice were subcutaneously injected with mixture phages clones. Sera Sm antibody, anti-double stranded DNA (dsDNA) antibody, and antinuclear antibody (ANA) of mice were detected using direct immunofluorescence; kidney histological changes were examined by HE staining.

RESULTSFive randomly selected peptides were sequenced and the amino acid sequences IR, SQ, and PP were detected in a higher frequency. High-titer IgG autoantibodies of dsDNA, Sm, and ANA in the sera of experiment group were detected by ELISA 28 days after having been immunized by Sm mimotope. Proteinuria was detected 33 days later; immune complex and nephritis were observed in kidney specimens.

CONCLUSIONSLE-like murine model can be successfully induced by Sm phage mimotope.

Animals ; Antibodies, Antinuclear ; blood ; Autoantibodies ; blood ; Disease Models, Animal ; Epitopes ; immunology ; Immunoglobulin G ; blood ; Lupus Erythematosus, Systemic ; immunology ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Oligopeptides ; immunology ; Peptide Library

To obtain peptides mimicking epitope of a protective McAb SSjl4 specific to Schistosoma japonicum and investigate their immuno-protection effects. A phage random 12 peptide library was screened using purified McAb SSj14, 33 clones were picked up for specificity identification by ELISA. The epitope of each positive clones were detected by the sequencing analysis technique. The antigenicity of three positive clones (P1, P2 and P11) and their mixture cock-tail were further confirmed by Western-blotting, and their protective efficiency were evaluated by mice vaccination experiment. IL-12 level between the vaccinated mice and control mice were compared. 30 positive phage clones were obtained, which represented 11 different epitopes respectively, there were a similar sequence "H-N/Q-X-S-P/F-X-X-L-A-T" among all of the epitopes. Western-blotting showed that all of the three tested clones were recognized by McAb SSj14. Significant adult worm reduction (13.84% to approximately 52.83%), liver tissue egg reduction (34.17% to approximately 65.47%) as well as fecal egg reduction (28.89% to approximately 73.78%) were observed in mice vaccinated with phages of P1, P2, P11 and mixture of three clones when compared with those of the blank control group, among them, the mice vaccinated with the mixture of phage clones got higher protection than any of the mice injected with only one kind of clone phages. At the same time, the IL-12 level in serum of vaccinated mice was found higher than those of the blank control one, this suggest that IL-12 may correlate with the protective efficiency induced by the clone phages. The study provides a new way for developing an effective vaccine against S. japonicum.
Animals ; Antibodies, Helminth ; immunology ; Antibodies, Monoclonal ; immunology ; Antigens, Helminth ; immunology ; Epitopes ; immunology ; Interleukin-12 ; blood ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Peptide Library ; Schistosoma japonicum ; immunology ; Schistosomiasis japonica ; immunology ; prevention & control ; Vaccination

Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, alpha-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.
Arthritis, Rheumatoid ; Autoantibodies ; Autoantigens ; Autoimmune Diseases* ; Autoimmunity ; Bacteria ; Bacterial Infections* ; Bacterial Proteins ; Clone Cells ; Collagen Type II ; Germinal Center ; Glucose-6-Phosphate Isomerase ; Heat-Shock Proteins ; Immunoglobulins ; Molecular Mimicry* ; Myeloblastin ; Phosphopyruvate Hydratase