scholarly journals Μελέτη λειτουργικών αυτοαντισωμάτων στη συστηματική αυτοανοσία

2015 ◽  
Author(s):  
Ιωάννης Γουλές
Keyword(s):  
Severe Disease ◽  
Cell Epitope ◽  
Clinical Manifestations ◽  
Cross Reactivity ◽  
Joint Fluid ◽  
Response To Treatment ◽  
Native Proteins ◽  
Cell Immunity ◽  
Citrullinated Peptide ◽  
Peptide Antibodies

Although the etiology of rheumatoid arthritis remains unclear, it seems that immunological, genetic and environmental factors are involved in pathogenesis. In the recent years, the role of anticitrullinated peptide antibodies (ACPA) has been studied extensively. Anti-citrullinated peptideantibodies are directed against citrullinated epitopes of native proteins as a result of conversion ofarginine to citrullin mediated by the action of specific enzymes called peptidyl arginine deiminases(PADs). Citrullination is considered a post-translational process occurring under certain conditionssuch as inflammation, apoptosis and smoking that induce the action of PADs. Human cells have 5isoforms of PAD with isoform 4 (PADI4) being involved in autoimmunity. Anti-citrullinated peptide antibodies are detected in serum of RA patients several years before the appearance of clinical manifestations and have been associated with erosive and severe disease. In clinical practice, anti-cyclic citrullinated petptide (anti-CCPs) antibodies have been used to reveal ACPA reactivity in sera of RA patients, although the sequence of CCPs remains unknown. Sensitivity of anti-CCPs for RA approximates 80% while specificity exceeds 95%. Anti-CCP antibodies are considered a collection of ACPA reflecting ACPA positivity and are used as a biomarker for RA diagnosis and response to treatment. Previous studies have shown that serum and/or joint fluid from RA patients react against citrullinated epitopes of different proteins such as vimentin, fibrinogen, aenolase, filaggrin and collagen. However no predominant B cell epitope has been identified yet. The aim of this study was to investigate whether ACPA constitute a homogenous population and if possible to identify the major citrullinated epitopes. We tested the reactivity of sera form 141 RA patients, against six distinct linear citrullinated peptides derived from the previous mentioned human proteins, by applying an ELISA protocol. The sequences of citrullinated peptides were carefully chosen based on data from previous studies. Citrullinated PADI4 was also included as anti-PADI4 antibodies have been found in the serum of RA patients while non-citrullinated PADI4 was used as a peptide control. Sera from 60 SLE patients, 54 Sjogren’s patients and 100 healthy volunteers were used as controls. We found that among RA patients, PAD211-30 displayed 29.08% sensitivity, vim60-75 29.08%, enol5-21 37.59%, fibrin617-31 31.21%, col-II358-75 29.97% and filaggrin306-24 28.37% while control ctrlPAD621- 40 showed no reactivity. Specificity for all citrullinated peptides ranged between 91-97%. The percentage of RA patients with reactivity against 1, 2, 3, 4, 5 or 6 citrullinated peptides was 61%, 45%, 31%, 24%, 17% and 5% respectively. Sensitivity for anti-CCP3 and the equamolar mixture containing all six citrullinated peptides was 60.78% and 46.08% respectively while specificity was found 94.12% and 82.22% respectively. By choosing two highly positive anti-CCP3 sera from RA patients, we tested specificity and cross reactivity of ACPA against the six citrullinated peptides. For both sera and almost all the peptides, homologous inhibition was found over 85%. Cross reactivity was minimal for both sera although a significant cross reaction (>70%) was observed mainly between filaggrin and the majority of anti-citrullinated-peptide antibodies. On the contrary, antifilaggrin and anti-alpha-enolase antibodies exhibited the least cross-reactivity and therefore might be considered the most specific for these two sera. We concluded that ACPA in RA constitute a heterogeneous population with limited cross reactivity and without a predominant epitope. Diversity of ACPA reactivity can be attributed to many factors including genetic features, epitope spreading, T cell immunity as well as the interference of the anti-idiotype antibodies. Future studies should be focused on different citrullinated epitopes mixtures and evaluate the contribution of cellular immunity in ACPA responses.

scholarly journals Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. Vuorela ◽  
T. L. Freitag ◽  
K. Leskinen ◽  
H. Pessa ◽  
T. Härkönen ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A ◽  
Strong Association ◽  
Cell Epitope ◽  
Cell Receptor ◽  
Cross Reactivity ◽  
Cell Immunity ◽  
Increased Risk ◽  
Influenza A H1n1

AbstractNarcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175–189 (NA175–189) and nucleoprotein 214–228 (NP214–228), but also respond to a NA175–189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675–689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175–189 or POMT1675–689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.

scholarly journals Genetic Analysis Reveals Differences in CD8+ T Cell Epitope Regions That May Impact Cross-Reactivity of Vaccine-Induced T Cells against Wild-Type Mumps Viruses

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 699
Author(s):  
Patricia Kaaijk ◽  
Maarten E. Emmelot ◽  
Jeroen Kerkhof ◽  
Cécile A.C.M. van Els ◽  
Hugo D. Meiring ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Critical Role ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Cd8 T Cell ◽  
Cross Reactivity ◽  
T Cell Epitope ◽  
Wild Type ◽  
Cell Immunity

Nowadays, mumps is re-emerging in highly vaccinated populations. Waning of vaccine-induced immunity plays a role, but antigenic differences between vaccine and mumps outbreak strains could also contribute to reduced vaccine effectiveness. CD8+ T cells play a critical role in immunity to viruses. However, limited data are available about sequence variability in CD8+ T cell epitope regions of mumps virus (MuV) proteins. Recently, the first set of naturally presented human leukocyte antigen Class I (HLA-I) epitopes of MuV was identified by us. In the present study, sequences of 40 CD8+ T cell epitope candidates, including previously and newly identified, obtained from Jeryl–Lynn mumps vaccine strains were compared with genomes from 462 circulating MuV strains. In 31 epitope candidates (78%) amino acid differences were detected, and in 17 (43%) of the epitope candidates the corresponding sequences in wild-type strains had reduced predicted HLA-I-binding compared to the vaccine strains. These findings suggest that vaccinated persons may have reduced T cell immunity to circulating mumps viruses due to antigenic differences.

scholarly journals Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity

2021 ◽  
Vol 1 ◽  
Author(s):  
Rhiane Moody ◽  
Kirsty L. Wilson ◽  
Jennifer C. Boer ◽  
Jessica K. Holien ◽  
Katie L. Flanagan ◽  
...  
Keyword(s):  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Function ◽  
Sequence Similarity ◽  
Severe Disease ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Cross Reactivity ◽  
B Cell Epitopes ◽  
Human Proteins

COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whilst commonly characterised as a respiratory disease, is reported to have extrapulmonary manifestations in multiple organs. Extrapulmonary involvement in COVID-19 includes autoimmune-like diseases such as Guillain-Barré syndrome and Kawasaki disease, as well as the presence of various autoantibodies including those associated with autoimmune diseases such a systemic lupus erythematosus (e.g. ANA, anti-La). Multiple strains of SARS-CoV-2 have emerged globally, some of which are found to be associated with increased transmissibility and severe disease. We performed an unbiased comprehensive mapping of the potential for cross-reactivity with self-antigens across multiple SARS-CoV-2 proteins and compared identified immunogenic regions across multiples strains. Using the Immune Epitope Database (IEDB) B cell epitope prediction tool, regions predicted as antibody epitopes with high prediction scores were selected. Epitope sequences were then blasted to eight other global strains to identify mutations within these regions. Of the 15 sequences compared, eight had a mutation in at least one other global strain. Predicted epitopes were then compared to human proteins using the NCBI blast tool. In contrast to studies focusing on short sequences of peptide identity, we have taken an immunological approach to selection criteria for further analysis and have identified 136 alignments of 6–23 amino acids (aa) in 129 human proteins that are immunologically likely to be cross-reactive with SARS-CoV-2. Additionally, to identify regions with significant potential to interfere with host cell function-or promote immunopathology, we identified epitope regions more likely to be accessible to pathogenic autoantibodies in the host, selected using a novel combination of sequence similarity, and modelling protein and alignment localization with a focus on extracellular regions. Our analysis identified 11 new predicted B-cell epitopes in host proteins, potentially capable of explaining key aspects of COVID-19 extrapulmonary pathology, and which were missed in other in silico studies which used direct identity rather than immunologically related functional criteria.

КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ ПИЩЕВЫХ АЛЛЕРГЕНОВ ЖИВОТНОГО ПРОИСХОЖДЕНИЯ

2019 ◽  
Author(s):  
A.N. Pampura ◽  
E.E. Varlamov
Keyword(s):  
Clinical Manifestations ◽  
Red Meat ◽  
Cross Reactivity ◽  
Allergic Reactions ◽  
Essential Nutrients ◽  
Animal Products ◽  
Food Animal ◽  
Mammalian Meat

Продукты животного происхождения обладают наиболее сбалансированным комплексом необходимых нутриентов, поэтому их включение в пищевой рацион оправданно в различные возрастные периоды. Клинические проявления аллергии к данным продуктам крайне разнообразны. Одним из ключевых аспектов обозначенной проблемы является диагностика и оценка вероятности развития перекрестной реактивности. К пищевым продуктам животного происхождения, наиболее часто индуцирующим симптомы, относятся коровье молоко, куриное яйцо, рыба, моллюски, ракообразные, мясо млекопитающих. В представленной статье изложены данные об основных классах пищевых аллергенов животного происхождения, индуцирующих развитие перекрестных аллергических реакций. Описаны синдромы, связанные с перекрестной реактивностью: птица-яйцо , кошка-свинина , рыба-курица и -Gal-синдром/ синдром красного мяса .Animal foods products contain the most balanced complex of essential nutrients. The clinical manifestations of allergy to these products are varied. Key aspect of this problem is diagnostics and assessment of cross-reactivity. The food animal products that more often induce symptoms include cows milk, hens egg, fish, mollusks, crustaceans, mammalian meat. Data on the main classes of food animal allergens inducing the development of cross-allergic reactions as well as syndromes associated with cross-reactivity like bird-egg , cat-pork , fish-chicken and a-Gal-syndrome/ red meat syndrome are described in this article.

Multiple Myeloma or Brucellosis: A Case Report

2020 ◽  
Vol 20 (1) ◽  
pp. 102-105 ◽  
Author(s):  
Hossein A. Rahdar ◽  
Mansoor Kodori ◽  
Mohamad R. Salehi ◽  
Mahsa Doomanlou ◽  
Morteza Karami-Zarandi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Brucella Melitensis ◽  
Severe Disease ◽  
Correct Diagnosis ◽  
Clinical Manifestations ◽  
Bone Marrow Aspiration ◽  
Major Health Problem ◽  
Brucella Infection ◽  
Wide Range ◽  
Parental Treatment

Background: Brucellosis, a major health problem in developing countries, is a multisystem infection with a broad spectrum of clinical manifestations. Hematological complications, ranging from an intravascular coagulopathy to mild homeostasis disorders (such as gammopathy), have been reported in brucella infection. These signs and symptoms may lead to misdiagnosis of brucellosis with other hematological diseases. Case: A 65-year-old male whose occupation was shepherding was referred to our hospital as a known case of multiple myeloma with continuous fever, muscle weakness, and night sweating after taking 2 courses of chemotherapy. The laboratory diagnosis of multiple myeloma had been based on the observation of a high percent of plasma cells in the bone marrow aspiration. At follow- up, the result of patient's fever workup, with 2 sets of blood cultures, was positive for Brucella melitensis. Isolated brucella was confirmed as B. melitensis by 16S rRNA sequencing. Brucellosis serologic test was performed by agglutination test and positive results were obtained. The patient was discharged with the cessation of fever and general improvement after the end of the parental treatment phase of brucella bacteremia. Conclusions: Brucella infection may cause a severe disease, mimicking a primary hematological disease, which could complicate the correct diagnosis. In brucellosis cases, due to the wide range of symptoms, in addition to cultivation and serological methods, molecular methods should also be used to prevent inappropriate diagnosis and additional costs.

The prevalence of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

2005 ◽  
Vol 0 (0) ◽  
Author(s):  
Sandra H. Machado ◽  
Carlos A. von Mühlen ◽  
João C. T. Brenol ◽  
Letícia Bisotto ◽  
Ricardo Machado Xavier
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Cyclic Citrullinated Peptide ◽  
Citrullinated Peptide ◽  
Peptide Antibodies

scholarly journals Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis

2012 ◽  
Vol 45 (6) ◽  
pp. 757-760 ◽  
Author(s):  
Elizabeth de Souza Neves ◽  
André Luis Land Curi ◽  
Maira Cavalcanti de Albuquerque ◽  
Cassius Schnel Palhano-Silva ◽  
Laura Berriel da Silva ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Case Control Study ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Nucleotide Polymorphism ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Duration Of Disease ◽  
Acute Toxoplasmosis ◽  
Control Study

INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.

Citrulline-independent positivity of anti cyclic citrullinated peptide antibodiES (ANTI-CCP) in type 1 autoimmune hepatitis (AIH-1)

2006 ◽  
Vol 38 (9) ◽  
pp. A83-A84
Author(s):  
A. Vannini ◽  
A.J.W. Zendman ◽  
A.C. Dall’Aglio ◽  
G. Ballardini ◽  
D. Zauli ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Cyclic Citrullinated Peptide ◽  
Citrullinated Peptide ◽  
Peptide Antibodies
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