Citrullination under physiological and pathological conditions

Baka, Zsuzsanna; György, Bence; Géher, Pál; Buzás, Edit I.; Falus, András; Nagy, György

doi:10.1016/j.jbspin.2012.01.008

Cited by 118 publications

(147 citation statements)

References 59 publications

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“…[161] SulfaƟon Sulphate [183] PolyglycylaƟon G lycine (up to 34) Glu > 75.067 G lycylase // Deglycylase [184,185] Other: CitrullinaƟon (conversion of Arg to citrulline by PAD enzyme) [186,187] [21,22,14 7] M1/K63 PolyUB Chain: C-t bond with N-t Met, Lys63 > 8565 [88,147] K6/K29/K33 PolyUB Chain: C-t bond with Lys6/Lys29/ Lys33 > 8565 K11/K27/K48 PolyUB Chain: C-t bond with Lys11/Lys27/ Lys48 > 8565…”

Section: Oxidaɵonmentioning

confidence: 99%

Post-translational add-ons mark the path in exosomal protein sorting

Moreno-Gonzalo

Fernández-Delgado

Sánchez‐Madrid

2017

Cell. Mol. Life Sci.

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Section: Oxidaɵonmentioning

confidence: 99%

Post-translational add-ons mark the path in exosomal protein sorting

Moreno-Gonzalo

Fernández-Delgado

Sánchez‐Madrid

2017

Cell. Mol. Life Sci.

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“…Thus, the study of pathways that modulate the inflammatory process could improve the current knowledge in sepsis physiopathology and identify potential therapeutic targets. In this scenario, the citrullination process has become a hot topic, and has been identified in several inflammatory diseases 2, 3…”

Section: Introductionmentioning

confidence: 99%

“…This enzymatic conversion has an important role in immune system function and in gene regulation 2, 3. In humans, there are five highly related calcium‐dependent PADs, which have been designated as PADs 1‐4 and PAD6.…”

Section: Introductionmentioning

confidence: 99%

“…PAD4 participates in post‐translational modifications of histones, one of the major focus areas of epigenetic research 2, 4. Citrullination of histones, in particular histone H3, is one of the major points for inflammatory signals that trigger the neutrophil response to infections 2, 3, 4, 5. Nevertheless, citrullinated histone H3 is also important in the development of neutrophils extracellular traps (NETs) 5, 6.…”

Section: Introductionmentioning

confidence: 99%

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Peptidylarginine deiminase 4 concentration, but not PADI4 polymorphisms, is associated with ICU mortality in septic shock patients

Costa

Gut

Azevedo

et al. 2018

J Cellular Molecular Medi

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The objective of our study was to evaluate the association between peptidylarginine deiminase 4 (PAD4) concentration and its polymorphisms with mortality in patients with septic shock. We prospectively evaluated 175 patients aged over 18 years with septic shock upon intensive care unit (ICU) admission. However, 48 patients were excluded. Thus, 127 patients were enrolled in the study. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentrations and its polymorphism PADI4_89 [rs11203366], PADI4_94 [rs2240340] and PADI4_104 [rs1748033]. The mean age was 63.3 ± 15.2 years, 56.7% were male, PAD4 concentration was 4.62 (2.48‐6.20) ng/mL and the ICU mortality rate was 67.7%. The patients who died in the ICU had higher APACHE II and Sequential Organ Failure Assessment (SOFA) scores. In addition, PAD4 concentration was higher in patients who died during ICU stay. However, there were no differences regarding PADI4 polymorphisms and ICU mortality. In the logistic regression models, PAD4 concentrations were associated with ICU mortality when adjusted for APACHE II score and lactate (OR: 1.477; CI 95%: 1.186‐1.839; P < .001), and when adjusted for age, gender and APACHE II score (OR: 1.392; CI 95%: 1.145‐1.692; P < .001). In conclusion, PAD4 concentration, but not PADI4_89, PADI4_94 and PADI4_104 polymorphisms, is associated with ICU mortality in septic shock patients.

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“…Citrullination is involved in many physiological processes in the body such as skin keratinization, maturation of hair follicles and insulation of nerve fibres (reviewed in [48]). Citrullination is also involved in pathological processes but although increased citrullination is found in the myelin sheaths in patients with multiple sclerosis (MS) and in lung cancer tissue, no antibodies to citrullinated proteins are found in these conditions [49].…”

Section: Citrullinationmentioning

confidence: 99%

Circulating and Mucosal Antibodies to Citrullinated Antigens in Rheumatoid Arthritis

Svärd¹

2014

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and subsequent destruction of cartilage and bone. The etiology is largely unknown, although genetic as well as environmental factors are involved. The manifestations and consequences of RA differ between individuals. This makes it important to find early markers for the disease course, in order to enable the most suitable treatment. IgG antibodies to cyclic citrullinated peptides (CCP) have high specificity for RA, but only around 60% of RA patients test positive for IgG anti-CCP. The aim of this thesis was to evaluate the usefulness of serum IgA anti-CCP as a diagnostic maker compared to IgG anti-CCP, and to assess IgA versus IgG anti-CCP status in relation to smoking habits and genetic background. Another aim was to evaluate signs of mucosal immunization by analyzing salivary IgA anti-CCP. IgA anti-CCP was present in a subgroup of RA patients with high levels of IgG anti-CCP and a slightly more severe disease course. Similar results were found regarding IgA class antibodies to modified citrullinated vimentin (MCV). IgG anti-MCV had slightly higher sensitivity for RA than IgG anti-CCP, thus identifying a group of IgG anti-CCP negative patients with an unfavourable disease course. However, the lower diagnostic specificity of IgG anti-MCV limits its usefulness. Among 63 patients with established RA, salivary IgA anti-CCP was found in 22% and was associated with a more favourable outcome regarding erosive joint disease at follow-up. IgA anti-CCP in serum was strongly associated with smoking, and the earlier known interaction between smoking and shared epitope (SE) was here shown to be valid only for subjects positive for IgA anti-CCP in combination with IgG anti-CCP. In conclusion, IgG anti-CCP is still the most useful serologic marker of RA, but IgA anti-CCP should be further investigated as a prognostic marker. The association between smoking and IgA anti-CCP strongly indicates a pathogenic role for smoking and IgA anti-CCP, supporting the possibility that RA may originate from chronic airway irritation. The less erosive disease in patients positive for salivary IgA anti-CCP indicates a protective role of secretory IgA anti-CCP

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Citrullination under physiological and pathological conditions

Cited by 118 publications

References 59 publications

Post-translational add-ons mark the path in exosomal protein sorting

Post-translational add-ons mark the path in exosomal protein sorting

Peptidylarginine deiminase 4 concentration, but not PADI4 polymorphisms, is associated with ICU mortality in septic shock patients

Circulating and Mucosal Antibodies to Citrullinated Antigens in Rheumatoid Arthritis

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