scholarly journals Post-Translational Modifications of Proteins: Novel Insights in the Autoimmune Response in Rheumatoid Arthritis

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 657 ◽  
Author(s):  
Francesco Carubbi ◽  
Alessia Alunno ◽  
Roberto Gerli ◽  
Roberto Giacomelli
Keyword(s):  
Rheumatoid Arthritis ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Autoimmune Response ◽  
Response To Treatment ◽  
Post Translational Modifications ◽  
Wide Range ◽  
Specific Proteins ◽  
Modified Proteins ◽  
Immunogenic Properties

Post-translational modifications (PTM) are chemical changes mostly catalyzed by enzymes that recognize specific target sequences in specific proteins. These modifications play a key role in regulating the folding of proteins, their targeting to specific subcellular compartments, their interaction with ligands or other proteins, and eventually their immunogenic properties. Citrullination is the best characterized PTM in the field of rheumatology, with antibodies anticyclic citrullinated peptides being the gold standard for the diagnosis of rheumatoid arthritis (RA). In recent years, growing evidence supports not only that a wide range of proteins are subject to citrullination and can trigger an autoimmune response in RA, but also that several other PTMs such as carbamylation and acetylation occur in patients with this disease. This induces a wide spectrum of autoantibodies, as biomarkers, with different sensitivity and specificity for diagnosis, which may be linked to peculiar clinical manifestations and/or response to treatment. The purpose of this review article is to critically summarize the available literature on antibodies against post-translationally modified proteins, in particular antibodies against citrullinated proteins (ACPA) and antibodies against modified proteins (AMPA), and outline their diagnostic and prognostic role to be implemented in clinical practice for RA patients.

scholarly journals Myasthenia Gravis: Autoantibody Specificities and Their Role in MG Management

2020 ◽  
Vol 11 ◽  
Author(s):  
Konstantinos Lazaridis ◽  
Socrates J. Tzartos
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Clinical Manifestations ◽  
Density Lipoprotein ◽  
Disease Diagnosis ◽  
Autoimmune Response ◽  
Response To Treatment ◽  
Antibody Detection ◽  
Serological Tests ◽  
The Past

Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction, characterized by skeletal muscle weakness and fatigability. It is caused by autoantibodies targeting proteins of the neuromuscular junction; ~85% of MG patients have autoantibodies against the muscle acetylcholine receptor (AChR-MG), whereas about 5% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). In the remaining about 10% of patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG). Since serological tests are relatively easy and non-invasive for disease diagnosis, the improvement of methods for the detection of known autoantibodies or the discovery of novel autoantibody specificities to diminish SN-MG and to facilitate differential diagnosis of similar diseases, is crucial. Radioimmunoprecipitation assays (RIPA) are the staple for MG antibody detection, but over the past years, using cell-based assays (CBAs) or improved highly sensitive RIPAs, it has been possible to detect autoantibodies in previously SN-MG patients. This led to the identification of more patients with antibodies to the classical antigens AChR and MuSK and to the third MG autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), while antibodies against other extracellular or intracellular targets, such as agrin, Kv1.4 potassium channels, collagen Q, titin, the ryanodine receptor and cortactin have been found in some MG patients. Since the autoantigen targeted determines in part the clinical manifestations, prognosis and response to treatment, serological tests are not only indispensable for initial diagnosis, but also for monitoring treatment efficacy. Importantly, knowing the autoantibody profile of MG patients could allow for more efficient personalized therapeutic approaches. Significant progress has been made over the past years toward the development of antigen-specific therapies, targeting only the specific immune cells or autoantibodies involved in the autoimmune response. In this review, we will present the progress made toward the development of novel sensitive autoantibody detection assays, the identification of new MG autoantigens, and the implications for improved antigen-specific therapeutics. These advancements increase our understanding of MG pathology and improve patient quality of life by providing faster, more accurate diagnosis and better disease management.

scholarly journals Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification

2019 ◽  
Vol 78 (7) ◽  
pp. 908-916 ◽  
Author(s):  
Arieke Suzanna Berendina Kampstra ◽  
Jacqueline Stephanie Dekkers ◽  
Mikhail Volkov ◽  
Annemarie L Dorjée ◽  
Lise Hafkenscheid ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Cell Response ◽  
Cross Reactivity ◽  
Single Type ◽  
Mutual Relationship ◽  
Post Translational Modifications ◽  
Modified Proteins ◽  
Relationship Of ◽  
Citrullinated Protein

ObjectivesAutoantibodies against post-translationally modified proteins (anti-modified protein antibodies or AMPAs) are a hallmark of rheumatoid arthritis (RA). A variety of classes of AMPAs against different modifications on proteins, such as citrullination, carbamylation and acetylation, have now been described in RA. At present, there is no conceptual framework explaining the concurrent presence or mutual relationship of different AMPA responses in RA. Here, we aimed to gain understanding of the co-occurrence of AMPA by postulating that the AMPA response shares a common ‘background’ that can evolve into different classes of AMPAs.MethodsMice were immunised with modified antigens and analysed for AMPA responses. In addition, reactivity of AMPA purified from patients with RA towards differently modified antigens was determined.ResultsImmunisation with carbamylated proteins induced AMPAs recognising carbamylated proteins and also acetylated proteins. Similarly, acetylated proteins generated (autoreactive) AMPAs against other modifications as well. Analysis of anti-citrullinated protein antibodies from patients with RA revealed that these also display reactivity to acetylated and carbamylated antigens. Similarly, anti-carbamylated protein antibodies showed cross-reactivity against all three post-translational modifications.ConclusionsDifferent AMPA responses can emerge from exposure to only a single type of modified protein. These findings indicate that different AMPA responses can originate from a common B-cell response that diversifies into multiple distinct AMPA responses and explain the presence of multiple AMPAs in RA, one of the hallmarks of the disease.

Ubiquitin and SUMO signalling in DNA repair

2010 ◽  
Vol 38 (1) ◽  
pp. 116-131 ◽  
Author(s):  
Timothy M. Thomson ◽  
Marta Guerra-Rebollo
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Translesion Synthesis ◽  
Strand Break ◽  
Cross Link ◽  
Post Translational Modifications ◽  
Nucleotide Excision ◽  
Specific Proteins ◽  
Modified Proteins

The repair of lesions and gaps in DNA follows different pathways, each mediated by specific proteins and complexes. Post-translational modifications in many of these proteins govern their activities and interactions, ultimately determining whether a particular pathway is followed. Prominent among these modifications are the addition of phosphate or ubiquitin (and ubiquitin-like) moieties that confer new binding surfaces and conformational states on the modified proteins. The present review summarizes some of consequences of ubiquitin and ubiquitin-like modifications and interactions that regulate nucleotide excision repair, translesion synthesis, double-strand break repair and interstrand cross-link repair, with the discussion of relevant examples in each pathway.

scholarly journals Microbiome Research and Multi-Omics Integration for Personalized Medicine in Asthma

2021 ◽  
Vol 11 (12) ◽  
pp. 1299
Author(s):  
Marianthi Logotheti ◽  
Panagiotis Agioutantis ◽  
Paraskevi Katsaounou ◽  
Heleni Loutrari
Keyword(s):  
Large Scale ◽  
Clinical Manifestations ◽  
Response To Treatment ◽  
Inflammatory Disorder ◽  
Host Interactions ◽  
Status Monitoring ◽  
Omics Integration ◽  
Wide Range ◽  
Microbiome Research ◽  
Global Understanding

Asthma is a multifactorial inflammatory disorder of the respiratory system characterized by high diversity in clinical manifestations, underlying pathological mechanisms and response to treatment. It is generally established that human microbiota plays an essential role in shaping a healthy immune response, while its perturbation can cause chronic inflammation related to a wide range of diseases, including asthma. Systems biology approaches encompassing microbiome analysis can offer valuable platforms towards a global understanding of asthma complexity and improving patients’ classification, status monitoring and therapeutic choices. In the present review, we summarize recent studies exploring the contribution of microbiota dysbiosis to asthma pathogenesis and heterogeneity in the context of asthma phenotypes–endotypes and administered medication. We subsequently focus on emerging efforts to gain deeper insights into microbiota–host interactions driving asthma complexity by integrating microbiome and host multi-omics data. One of the most prominent achievements of these research efforts is the association of refractory neutrophilic asthma with certain microbial signatures, including predominant pathogenic bacterial taxa (such as Proteobacteria phyla, Gammaproteobacteria class, especially species from Haemophilus and Moraxella genera). Overall, despite existing challenges, large-scale multi-omics endeavors may provide promising biomarkers and therapeutic targets for future development of novel microbe-based personalized strategies for diagnosis, prevention and/or treatment of uncontrollable asthma.

scholarly journals Novel autoantibodies in rheumatoid arthritis

Reumatismo ◽  
2019 ◽  
Vol 71 (1) ◽  
pp. 1-12 ◽  
Author(s):  
A.F. Bonifacio ◽  
A. Alunno ◽  
G.M.C. La Paglia ◽  
E. Valentini ◽  
M.C. Leone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Relevant Literature ◽  
Prognostic Significance ◽  
Review Article ◽  
Autoimmune Response ◽  
Native Form ◽  
Post Translational Modifications

Rheumatoid factor and antibodies against cyclic citrullinated peptides represent a diagnostic hallmark in rheumatoid arthritis (RA). However, over the last decades many other autoantibodies have been identified. Several proteins can trigger an aberrant autoimmune response in their native form while others acquire this feature after post-translational modifications such as citrullination, carbamylation or acetylation. It is of interest that also the enzymes catalyzing such post-translational modifications (e.g. the protein arginine deiminases) can transform themselves into autoantibodies in RA. The purpose of this review article is to provide an overview of relevant literature published over the last years regarding novel autoantibodies and their possible diagnostic and prognostic significance in RA.

scholarly journals Protein Methylation and Stress Granules: Posttranslational Remodeler or Innocent Bystander?

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Wen Xie ◽  
Robert B. Denman
Keyword(s):  
Stress Granules ◽  
Stress Granule ◽  
Protein Methylation ◽  
Innocent Bystander ◽  
Post Translational Modifications ◽  
Specific Proteins ◽  
Modified Proteins ◽  
And Function

Stress granules contain a large number of post-translationally modified proteins, and studies have shown that these modifications serve as recruitment tags for specific proteins and even control the assembly and disassembly of the granules themselves. Work originating from our laboratory has focused on the role protein methylation plays in stress granule composition and function. We have demonstrated that both asymmetrically and symmetrically dimethylated proteins are core constituents of stress granules, and we have endeavored to understand when and how this occurs. Here we seek to integrate this data into a framework consisting of the currently known post-translational modifications affecting stress granules to produce a model of stress granule dynamics that, in turn, may serve as a benchmark for understanding and predicting how post-translational modifications regulate other granule types.

scholarly journals Recurrent Trichosporon asahii Glossitis: A Case Report

2008 ◽  
Vol 9 (3) ◽  
pp. 114-120 ◽  
Author(s):  
Ban Tawfeek Shareef ◽  
Azian Harun ◽  
Yusof Roziawati ◽  
Ismail Shaiful Bahari ◽  
Zakuan Zainy Deris ◽  
...  
Keyword(s):  
Case Report ◽  
Wide Spectrum ◽  
Antifungal Susceptibility ◽  
Resistance Mechanism ◽  
Clinical Manifestations ◽  
Superficial Infection ◽  
Trichosporon Asahii ◽  
Clinical Presentations ◽  
Wide Range ◽  
Oral Environment

Abstract Aim This case report aims at describing an infection of the tongue as a manifestation of a Trichosporon asahii infection, its association with bronchial asthma and steroid administration, and to present a review of the literature pertaining to its antifungal susceptibility profile. Background Trichosporon asahii has been reported to be associated with a wide spectrum of clinical manifestations, ranging from superficial infection to severe disseminated diseases, particularly in immunocompromised patients. Case Report A 36-year-old male asthmatic patient with recurrent glossitis presented with a chief complaint of burning sensation and two red areas on the dorsum of the tongue of three months duration. The glossitis was associated with Trichosporon asahii, which had a reduced susceptibility to some azole antifungal agents. Summary Trichosporon asahii is an emerging fungal pathogen which may cause a wide range of clinical manifestations. More reports on its various clinical presentations in the oral environment need to be made available in the literature. To date there is a paucity of data on its prevalence, pathogenesis, and antifungal resistance mechanism. Citation Shareef BT, Harun A, Roziawati Y, Shaiful Bahari I, Deris ZZ, Ravichandran M. Recurrent Trichosporon asahii Glossitis: A Case Report. J Contemp Dent Pract 2008 March; (9)3:114-120.

scholarly journals Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Federica Ciregia ◽  
Dominique Baiwir ◽  
Gaël Cobraiville ◽  
Thibaut Dewael ◽  
Gabriel Mazzucchelli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Binding Protein ◽  
Protein Glycosylation ◽  
Response To Treatment ◽  
Healthy Controls ◽  
Lipopolysaccharide Binding Protein ◽  
Post Translational Modifications ◽  
Corticosteroid Binding Globulin ◽  
Serum Lectin ◽  
Lipopolysaccharide Binding

Abstract Background Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls. Methods In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC–MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90). Results We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. Conclusions This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

scholarly journals Sturge Weber Syndrome – Roach’s Type II Variant

2020 ◽  
Vol 18 (1) ◽  
pp. 76-79
Author(s):  
Muna Bista ◽  
Sudha Agrawal ◽  
Sweta Taparia
Keyword(s):  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Corneal Edema ◽  
Congenital Glaucoma ◽  
Type Ii ◽  
Ophthalmic Manifestations ◽  
Wide Range ◽  
Weber Syndrome ◽  
History Of ◽  
Sturge Weber Syndrome

Sturge-Weber syndrome (SWS) is a neurocutaneous sporadic disorder caused by mutation in GNAQ gene responsible for persistence of vascular plexus around cephalic portion of neural tube. It has a wide spectrum of cutaneous, neurologic and ophthalmic manifestations, which may or may not be associated with one another. Roach scale has classified it into three types. Here, we present a case of Roach’s Type II variant of SWS with Port-wine stain (PWS) and ocular abnormalities without Central Nervous System (CNS) involvement. A 24 months old female presented with hemangioma involving the left side of face since birth. She had history of corneal edema and buphthalmos at two days of life. There was no history of seizure or developmental delay and Magnetic Resonance Imaging (MRI) of the head ruled out cranial hemangioma. Roach’s Type II is a rare variant of SWS and should be suspected in any case having PWS along the course of trigeminal nerve with congenital glaucoma because the neurologic involvement in a given case may vary from an absence to overt clinical manifestations with or without radiological changes. Due to its wide range of manifestations, a multidisciplinary approach is required for proper management of these patients.

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