molecular mimicry
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2022 ◽  
Tobias V Lanz ◽  
R Camille Brewer ◽  
Peggy P Ho ◽  
Kevin M Jude ◽  
Daniel Fernandez ◽  

Abstract Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system (CNS). B lymphocytes in the cerebrospinal fluid (CSF) of MS patients contribute to inflammation and secrete oligoclonal immunoglobulins. Epstein-Barr virus (EBV) infection has been linked to MS epidemiologically, but its pathological role remains unclear. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBNA1 and the CNS protein GlialCAM, and provide structural and in-vivo functional evidence for its relevance. A cross-reactive CSF-derived antibody was initially identified by single-cell sequencing of the paired-chain B cell repertoire of MS blood and CSF, followed by protein microarray-based testing of recombinantly expressed CSF-derived antibodies against MS-associated viruses. Sequence analysis, affinity measurements, and the crystal structure of the EBNA1-peptide epitope in complex with the autoreactive Fab fragment allowed for tracking the development of the naïve EBNA1-restricted antibody to a mature EBNA1/GlialCAM cross-reactive antibody. Molecular mimicry is facilitated by a post-translational modification of GlialCAM. EBNA1 immunization exacerbates the mouse model of MS and anti-EBNA1/GlialCAM antibodies are prevalent in MS patients. Our results provide a mechanistic link for the association between MS and EBV, and could guide the development of novel MS therapies.

Science ◽  
2022 ◽  
Young-Jun Park ◽  
Anna De Marco ◽  
Tyler N. Starr ◽  
Zhuoming Liu ◽  
Dora Pinto ◽  

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 77
Anca Bobircă ◽  
Florin Bobircă ◽  
Ioan Ancuța ◽  
Anca Florescu ◽  
Mihai Bojincă ◽  

Thrombocytopenia is defined as a platelet count below 150,000/mm3 for adults. There is still controversy about whether individuals with platelet counts of 100,000/mm3 to 150,000/mm3 should be classified as having genuine thrombocytopenia or borderline thrombocytopenia. Thrombocytopenia is considered mild when the platelet count is between 70,000 and 150,000/mm3 and severe if the count is less than 20,000/mm3. Thrombocytopenia in rheumatoid arthritis is a rare complication, with an incidence estimated between 3 and 10%. The main etiological aspects include drug-induced thrombocytopenia and immune thrombocytopenic purpura. The most common hematological abnormalities in SARS-CoV-2 infection are lymphopenia and thrombocytopenia. It has been observed that the severity of thrombocytopenia correlates with the severity of the infection, being a poor prognosis indicator and a risk factor for mortality. COVID-19 can stimulate the immune system to destroy platelets by increasing the production of autoantibodies and immune complexes. Autoimmunity induced by viral infections can be related to molecular mimicry, cryptic antigen expression and also spreading of the epitope. During the COVID-19 pandemic, it is of great importance to include the SARS-CoV-2 infection in differential diagnoses, due to the increased variability in forms of presentation of this pathology. In this review, our aim is to present one of the most recently discovered causes of thrombocytopenia, which is the SARS-CoV-2 infection and the therapeutic challenges it poses in association with an autoimmune disease such as rheumatoid arthritis.

2021 ◽  
Vol 14 (1) ◽  
pp. 34-48
Abdullah Ahmad Tawakul ◽  
Amal Waleed Al-Doboke ◽  
Shahad Ali Altayyar ◽  
Seham Abdulhafith Alsulami ◽  
Ahlam Musallam Alfahmi ◽  

There have been several reported cases of severe acute respiratory syndrome (SARS-CoV-2) infection that were associated with an increased incidence of neurological manifestations, including Guillain–Barré syndrome (GBS). This review aims to present information on the reports of GBS associated with coronavirus disease 2019 (COVID-19) infection. Our review is retrospective work examining articles published from the 1 April 2020 to the 8 May 2021 in the English language. We used the diagnostic criteria and classification published by the National Institute of Neurological Disorders and Stroke and Brighton Collaboration. GBS is usually a postinfectious syndrome, but GBS in the COVID-19 pandemic also takes on a para-infectious profile. In the reports, the genetic factor has a role in developing GBS in some patients. In conclusion, the association between COVID-19 and GBS is not very clear. Still, one mechanism is strongly associated with COVID-19 and immune-mediated neurological complications, which is molecular mimicry between SARS-CoV-2 and human autoantigens.

Jonas D. Albarnaz ◽  
Hongwei Ren ◽  
Alice A. Torres ◽  
Evgeniya V. Shmeleva ◽  
Carlos A. Melo ◽  

2021 ◽  
Vol 9 (1) ◽  
pp. 40
Vineet Sehgal ◽  
Lucky Bhalla ◽  
Priyanshu Bansal ◽  
Shaifali Arora

Dengue is a common mosquito-borne infection in India. We reported a rare Pharyngeal cervical brachial (PCB) variant of Landry Guillain Barre syndrome (LGBS) associated with the dengue virus infection. The pathogenesis seems to be molecular mimicry between gangliosides and microbial lipo-oligosaccharides. PCB usually presents with oropharyngeal or cervicobrachial weakness. Therefore, it must be recognised early and distinguished from conditions presenting with cephalocaudal progressing weakness, such as Myasthenia Gravis, Miller-Fisher syndrome, botulism, diphtheria, porphyria or brain stem stroke. The aim of the study was to add to the limited literature on the PCB variant of LGBS after dengue infection and shed some light on presentation and management options for this rare entity.

2021 ◽  
Vol 8 ◽  
Michael Kasperkiewicz ◽  
Marta Bednarek ◽  
Stefan Tukaj

It is hypothesized that SARS-CoV-2 has the potential to elicit autoimmunity due to molecular mimicry between immunogenic proteins of the virus and human extracellular molecules. While in silico and in vitro evaluation of such immune cross-reactivity of human antibodies to SARS-CoV-2 proteins with several different tissue antigens has been described, there is limited information specifically pertaining to the immunological effects of COVID-19 and vaccines against SARS-CoV-2 on the development of autoimmune bullous diseases (AIBDs). Twelve seropositive post-COVID-19 individuals and 12 seropositive healthy volunteers who received two doses of the mRNA COVID-19 vaccine from Pfizer-BioNTech have been included in this case series investigation. Serum samples of these blood donors were tested for autoantibodies to the main immunobullous autoantigens, i.e., desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen. Our study revealed that none of the 24 anti-SARS-CoV-2 IgG-positive subjects had concomitant antibody reactivity with any of the tested autoantigens. These results argue against a relationship between SARS-CoV-2 infection/vaccines and AIBDs with respect to disease-triggering antibody cross-reactivity.

2021 ◽  
Vol 23 (6) ◽  
pp. 1239-1270
M. Z. Saidov

Cell infiltrate is a morphological substrate of immunoinflammatory rheumatic diseases. The systemic wide progressive disorganization of loose fibrous connective tissue is accompanied by the loss of tolerance with its own autoantigenes, activation of macrophagal-monocyte cells and autoreactive clones of T and B lymphocytes. Hyperproduction of pro-inflammatory chemokines and cytokines, local adhesive ligandreceptor interactions, endothelial reaction and angiogenesis contribute to the formation of cell infiltrate, ectopic lymphoid structures and GZT-granulomas in situ. The autoimmune response is the result of successive systemic and local molecular cellular events in which the mechanisms of congenital and adaptive immunity are involved. When interpreting immunopathogenesis of rheumatic diseases, all models and schemes adopted in the field of fundamental immunology are used. This is a model of MHC-restrictions, a model of molecular mimicry, or cross of the antigen presentation, a model of disrupting central or peripheral tolerance to auto-antigens, a model of candidate “triggers” of autoimmune and autoinflammatory processes, a model of associations of alleles MHC I and II classes with specific, nosologically unique, rheumatic diseases.

2021 ◽  
Vol 2 (5) ◽  
Vivek Satyasi ◽  
Aiesha Ahmed ◽  
Amtul Farheen

We describe a rare case presenting with both signs of acute motor and sensory axonal neuropathy (AMSAN) and immune thrombocytopenic purpura (ITP) possibly triggered by Hemophilus influenzae. Guillain-Barre is an autoimmune disorder purported to be due to molecular mimicry, often with a preceding infection, leading to myelin sheath or even axonal damage, AMSAN, in the peripheral nervous system (PNS). Rarely, there have been case reports of concurrent acute autoimmune disorders leading to a more complex presentation and additional comorbidities. A 42-year-old man presented with 2 days of progressive lower and upper extremity paresthesia’s, ataxia preceded by an upper respiratory infection. Examination showed areflexia and purpura, recent oral mucosal hemorrhage. Lab results showed severe thrombocytopenia suspicious for ITP. Over the ensuing weeks while inpatient, his condition quickly deteriorated to requiring an intubation for respiratory failure and not immediately responsive to IVIG. Recovery, both for AMSAN confirmed by EMG and ITP, was eventually achieved with time and five treatments of plasmapheresis and eventually was discharged to a rehabilitation facility. A thorough infectious workup revealed a possible trigger being Haemophilus influenzae. There have been rare occasions of concurrent GBS and ITP, but even more rare is the presence of both AMSAN and ITP which requires quick recognition and evaluation. This case highlights the need for a thorough initial history taking and a general physical exam, in addition to unique management decisions and strategies in patients with suspected GBS as there may be signs of other associated disorders that require immediate attention.

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