Immunoproteomic identification of antigenic candidate Campylobacter jejuni and human peripheral nerve proteins involved in Guillain-Barré syndrome

Loshaj-Shala, Aida; Colzani, Mara; Brezovska, Katerina; Panovska, Ana Poceva; Šuturkova, Ljubica; Beretta, Giangiacomo

doi:10.1016/j.jneuroim.2018.01.006

Cited by 18 publications

(9 citation statements)

References 52 publications

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“…Mitochondrial dysfunction appears important in many neurodegenerative disorders. ATP5b autoantibody was found in both the Guillain-Barre syndrome and Alzheimer's disease ( 30 , 31 ). It would be interesting to study these relationships between the bacterial proteins and the human mitochondrial functions in various neurodegenerative disorders.…”

Section: Specific Antibodies Against Microbial Proteinsmentioning

confidence: 99%

Anti-microbial Antibodies, Host Immunity, and Autoimmune Disease

Zhang¹,

Minardi²,

Kuenstner³

et al. 2018

Front. Med.

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Autoimmune diseases are a spectrum of clinical inflammatory syndromes with circulating autoantibodies. Autoimmune diseases affect millions of patients worldwide with enormous costs to patients and society. The diagnosis of autoimmune diseases relies on the presence of autoantibodies and the treatment strategy is to suppress the immune system using specific or non-specific immunosuppressive agents. The discovery of anti-microbial antibodies in the blood of patients with Crohn's disease and Sjogren's syndrome and cross-reactivity of anti-microbial antibodies to human tissue suggests a new molecular mechanism of pathogenesis, raising the possibility of designing a new therapeutic strategy for these patients. The presence of anti-microbial antibodies indicates the failure of the innate immunity system to clear the microbial agents from the blood and activation of adaptive immunity through B-lymphocytes/plasma cells. More importantly, the specific antibodies against the microbial proteins are directed toward the commensal microbes commonly present on the surface of the human host, and these commensal microbes are important in shaping the development of the immune system and in maintaining the interaction between the human host and the environment. Persistence of these anti-microbial antibodies in patients but not in normal healthy individuals suggests abnormal interaction between the human host and the commensal microbes in the body. Elimination of the organism/organisms that elicits the antibody response would be a new avenue of therapy to investigate in patients with autoimmune diseases.

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Section: Specific Antibodies Against Microbial Proteinsmentioning

confidence: 99%

Anti-microbial Antibodies, Host Immunity, and Autoimmune Disease

Zhang¹,

Minardi²,

Kuenstner³

et al. 2018

Front. Med.

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“…This analysis also identified 34 antigens that were specifically recognized by only the anti- C . jejuni antisera including CjaA and three other previously identified antigens, AhpC and Adk [52], and AmaA [29] (Table 1). None of the 34 specific antigens reacted to pooled human sera obtained from 10 healthy individuals.…”

Section: Resultsmentioning

confidence: 99%

A proteome-wide screen of Campylobacter jejuni using protein microarrays identifies novel and conformational antigens

Liu¹,

Parrish²,

Hines³

et al. 2019

PLoS ONE

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Campylobacter jejuni (C. jejuni) is a foodborne intestinal pathogen and major cause of gastroenteritis worldwide. C. jejuni proteins that are immunogenic have been sought for their potential use in the development of biomarkers, diagnostic assays, or subunit vaccines for humans or livestock. To identify new immunogenic C. jejuni proteins, we used a native protein microarray approach. A protein chip, with over 1400 individually purified GST-tagged C. jejuni proteins, representing over 86% of the proteome, was constructed to screen for antibody titers present in test sera raised against whole C. jejuni cells. Dual detection of GST signals was incorporated as a way of normalizing the variation of protein concentrations contributing to the antibody staining intensities. We detected strong signals to 102 C. jejuni antigens. In addition to antigens recognized by antiserum raised against C. jejuni, parallel experiments were conducted to identify antigens cross-reactive to antiserum raised against various serotypes of E. coli or Salmonella or to healthy human sera. This led to the identification of 34 antigens specifically recognized by the C. jejuni antiserum, only four of which were previously known. The chip approach also allowed identification of conformational antigens. We demonstrate in the case of Cj1621 that antigen signals are lost to denaturing conditions commonly used in other approaches to identify immunogens. Antigens identified in this study include those possessing sequence features indicative of cell surface localization, as well as those that do not. Together, our results indicate that the unbiased chip-based screen can help reveal the full repertoire of host antibodies against microbial proteomes.

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“…Hsp60 from a bacterium infecting the intestinal or the genitourinary tract), and also with human Hsp60 and other human molecules [54]. This type of autoimmunity caused by molecular mimicry with Hsp60 as the main suspect has been described for a range of disorders such as chlamydial infections [55,56], myasthenia gravis [57,58], periodontitis [59,60], Hashimoto's thyroiditis [61,62], Guillain-Barré syndrome [63,64], and gastritis with Helicobacter pylori [65]. (2) Ulcerative colitis is another example in which association of Hsp60 levels in the intestinal mucosa closely correlates with inflammatory status, high in relapse and low in remission [66,67].…”

Section: Hsp60 Modificationsmentioning

confidence: 99%

Molecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapies

Macario

2019

The Journal of Pathology

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Molecular chaperones, many of which are heat shock proteins (Hsps), are components of the chaperoning system and when defective can cause disease, the chaperonopathies. Chaperone-gene variants cause genetic chaperonopathies, whereas in the acquired chaperonopathies the genes are normal, but their protein products are not, due to aberrant post-transcriptional mechanisms, e.g. post-translational modifications (PTMs). Since the chaperoning system is widespread in the body, chaperonopathies affect various tissues and organs, making these diseases of interest to a wide range of medical specialties. Genetic chaperonopathies are uncommon but the acquired ones are frequent, encompassing various types of cancer, and inflammatory and autoimmune disorders. The clinical picture of chaperonopathies is known. Much less is known on the impact that pathogenic mutations and PTMs have on the properties and functions of chaperone molecules. Elucidation of these molecular alterations is necessary for understanding the mechanisms underpinning the tissue and organ abnormalities occurring in patients. To illustrate this issue, we discuss structural-functional alterations caused by mutation in the chaperones CCT5 and HSPA9, and PTM effects on Hsp60. The data provide insights into what may happen when CCT5 and HSPA9 malfunction in patients, e.g. accumulation of cytotoxic protein aggregates with tissue destruction; or for Hsp60 with aberrant PTM, degradation and/or secretion of the chaperonin with mitochondrial damage. These and other possibilities are now open for investigation.The canonical functions of chaperones pertain to the maintenance of protein homeostasis, in essence protein-quality control; for example: assisting in the correct folding of nascent polypeptides, ushering polypeptides to their place of residence including through membranes, helping partially denatured

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Immunoproteomic identification of antigenic candidate Campylobacter jejuni and human peripheral nerve proteins involved in Guillain-Barré syndrome

Cited by 18 publications

References 52 publications

Anti-microbial Antibodies, Host Immunity, and Autoimmune Disease

Anti-microbial Antibodies, Host Immunity, and Autoimmune Disease

A proteome-wide screen of Campylobacter jejuni using protein microarrays identifies novel and conformational antigens

Molecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapies

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