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Petri Lehenkari - One of the best experts on this subject based on the ideXlab platform.

Juha Risteli - One of the best experts on this subject based on the ideXlab platform.

  • rheumatoid arthritis antigens Homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2 3 and 4 in rheumatoid nodule and synovial tissue
    Arthritis Research & Therapy, 2016
    Co-Authors: Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
    Abstract:

    Background Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase.

  • rheumatoid arthritis antigens Homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2 3 and 4 in rheumatoid nodule and synovial tissue
    Arthritis Research & Therapy, 2016
    Co-Authors: Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
    Abstract:

    Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and Homocitrulline contents using HPLC. The location of citrulline- and Homocitrulline-containing proteins, PAD 2, 3, 4 and myeloperoxidase were shown by immunostaining. Myeloperoxidase and citrulline- or Homocitrulline-containing proteins were stained on Western blot. Overall, necrosis was frequent in metatarsals of seropositive RA and absent in seronegative RA and osteoarthritis patients. In histological analysis, there was a significant local patterning and variation in the citrulline and Homocitrulline content and it was highest in metatarsal synovial tissues of seropositive RA patients. We found peptidyl arginine deiminase 2, 3 and 4 in the lining and sublining layers of intact synovial tissue. Myeloperoxidase was found locally around necrotic areas. The tissues with necrosis contained the highest levels of citrulline and Homocitrulline. Rheumatoid nodules and synovia contain significant amount of PAD2, 3 and 4 and myeloperoxidase enzymes. These enzymes could explain the levels of citrulline and Homocitrulline in seropositive RA synovial and rheumatoid nodule tissues especially around necrotic tissue.

  • ureido group specific antibodies are induced in rabbits immunized with citrulline or Homocitrulline containing antigens
    Autoimmunity, 2016
    Co-Authors: Sanna Turunen, Marjakaisa Koivula, Leila Risteli, Juha Risteli
    Abstract:

    AbstractThe specificities and cross-reactions of antibodies induced by citrulline- and Homocitrulline-containing proteins may give implications on the role of citrulline- and Homocitrulline-binding antibodies in the pathogenesis and progression of rheumatoid arthritis (RA). Here we use rabbits as an experimental model of antibody development in RA. Thirty-two animals were immunized with peptide antigens containing either Homocitrulline or citrulline. The sera were tested for binding to CCP and MCV antigens and to peptide sequences related to carboxyterminal telopeptides of type I and II collagens and containing arginine, citrulline, or Homocitrulline. The binding of CCP and MCV antigens to antisera against Homocitrulline-containing immunogens could be inhibited by human serum albumin containing Homocitrulline, whereas similar binding to sera against citrulline-containing immunogens was not inhibited. The antisera induced with citrulline-containing collagen telopeptides recognized type I collagen-related a...

  • separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline and Homocitrulline containing peptides related to type i and ii collagen telopeptides
    Arthritis Research & Therapy, 2015
    Co-Authors: Sanna Turunen, Juha Risteli, Marjakaisa Koivula, Leila Risteli, Pekka Hannonen
    Abstract:

    Introduction Our objective was to find out if there are antibodies binding to Homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and Homocitrulline in the same peptide sequence.

  • Homocitrulline an analog and confounder related to citrulline
    2014
    Co-Authors: Sanna Turunen, Marjakaisa Koivula, Leila Risteli, Anthony P Nicholas, Juha Risteli
    Abstract:

    A structural homolog to citrulline, Homocitrulline, can be present in proteins and peptides as a product of posttranslational modification. Homocitrulline is formed nonenzymatically from lysine residues in the polypeptide chain by the action of cyanate. The latter compound is derived either from urea or, via a reaction catalyzed by the enzyme myeloperoxidase (MPO), from thiocyanate. The formation of Homocitrulline is known as carbamoylation or carbamylation. In humans, this process takes place predominantly in two types of situations: uremia and inflammation. Smoking increases the circulating thiocyanate concentration and thus enhances carbamoylation of proteins.

Sanna Turunen - One of the best experts on this subject based on the ideXlab platform.

  • rheumatoid arthritis antigens Homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2 3 and 4 in rheumatoid nodule and synovial tissue
    Arthritis Research & Therapy, 2016
    Co-Authors: Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
    Abstract:

    Background Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase.

  • rheumatoid arthritis antigens Homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2 3 and 4 in rheumatoid nodule and synovial tissue
    Arthritis Research & Therapy, 2016
    Co-Authors: Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
    Abstract:

    Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and Homocitrulline contents using HPLC. The location of citrulline- and Homocitrulline-containing proteins, PAD 2, 3, 4 and myeloperoxidase were shown by immunostaining. Myeloperoxidase and citrulline- or Homocitrulline-containing proteins were stained on Western blot. Overall, necrosis was frequent in metatarsals of seropositive RA and absent in seronegative RA and osteoarthritis patients. In histological analysis, there was a significant local patterning and variation in the citrulline and Homocitrulline content and it was highest in metatarsal synovial tissues of seropositive RA patients. We found peptidyl arginine deiminase 2, 3 and 4 in the lining and sublining layers of intact synovial tissue. Myeloperoxidase was found locally around necrotic areas. The tissues with necrosis contained the highest levels of citrulline and Homocitrulline. Rheumatoid nodules and synovia contain significant amount of PAD2, 3 and 4 and myeloperoxidase enzymes. These enzymes could explain the levels of citrulline and Homocitrulline in seropositive RA synovial and rheumatoid nodule tissues especially around necrotic tissue.

  • ureido group specific antibodies are induced in rabbits immunized with citrulline or Homocitrulline containing antigens
    Autoimmunity, 2016
    Co-Authors: Sanna Turunen, Marjakaisa Koivula, Leila Risteli, Juha Risteli
    Abstract:

    AbstractThe specificities and cross-reactions of antibodies induced by citrulline- and Homocitrulline-containing proteins may give implications on the role of citrulline- and Homocitrulline-binding antibodies in the pathogenesis and progression of rheumatoid arthritis (RA). Here we use rabbits as an experimental model of antibody development in RA. Thirty-two animals were immunized with peptide antigens containing either Homocitrulline or citrulline. The sera were tested for binding to CCP and MCV antigens and to peptide sequences related to carboxyterminal telopeptides of type I and II collagens and containing arginine, citrulline, or Homocitrulline. The binding of CCP and MCV antigens to antisera against Homocitrulline-containing immunogens could be inhibited by human serum albumin containing Homocitrulline, whereas similar binding to sera against citrulline-containing immunogens was not inhibited. The antisera induced with citrulline-containing collagen telopeptides recognized type I collagen-related a...

  • separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline and Homocitrulline containing peptides related to type i and ii collagen telopeptides
    Arthritis Research & Therapy, 2015
    Co-Authors: Sanna Turunen, Juha Risteli, Marjakaisa Koivula, Leila Risteli, Pekka Hannonen
    Abstract:

    Introduction Our objective was to find out if there are antibodies binding to Homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and Homocitrulline in the same peptide sequence.

  • Homocitrulline an analog and confounder related to citrulline
    2014
    Co-Authors: Sanna Turunen, Marjakaisa Koivula, Leila Risteli, Anthony P Nicholas, Juha Risteli
    Abstract:

    A structural homolog to citrulline, Homocitrulline, can be present in proteins and peptides as a product of posttranslational modification. Homocitrulline is formed nonenzymatically from lysine residues in the polypeptide chain by the action of cyanate. The latter compound is derived either from urea or, via a reaction catalyzed by the enzyme myeloperoxidase (MPO), from thiocyanate. The formation of Homocitrulline is known as carbamoylation or carbamylation. In humans, this process takes place predominantly in two types of situations: uremia and inflammation. Smoking increases the circulating thiocyanate concentration and thus enhances carbamoylation of proteins.

Johanna Huhtakangas - One of the best experts on this subject based on the ideXlab platform.

  • rheumatoid arthritis antigens Homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2 3 and 4 in rheumatoid nodule and synovial tissue
    Arthritis Research & Therapy, 2016
    Co-Authors: Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
    Abstract:

    Background Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase.

  • rheumatoid arthritis antigens Homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2 3 and 4 in rheumatoid nodule and synovial tissue
    Arthritis Research & Therapy, 2016
    Co-Authors: Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
    Abstract:

    Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and Homocitrulline contents using HPLC. The location of citrulline- and Homocitrulline-containing proteins, PAD 2, 3, 4 and myeloperoxidase were shown by immunostaining. Myeloperoxidase and citrulline- or Homocitrulline-containing proteins were stained on Western blot. Overall, necrosis was frequent in metatarsals of seropositive RA and absent in seronegative RA and osteoarthritis patients. In histological analysis, there was a significant local patterning and variation in the citrulline and Homocitrulline content and it was highest in metatarsal synovial tissues of seropositive RA patients. We found peptidyl arginine deiminase 2, 3 and 4 in the lining and sublining layers of intact synovial tissue. Myeloperoxidase was found locally around necrotic areas. The tissues with necrosis contained the highest levels of citrulline and Homocitrulline. Rheumatoid nodules and synovia contain significant amount of PAD2, 3 and 4 and myeloperoxidase enzymes. These enzymes could explain the levels of citrulline and Homocitrulline in seropositive RA synovial and rheumatoid nodule tissues especially around necrotic tissue.

Philippe Gillery - One of the best experts on this subject based on the ideXlab platform.

  • measurement of Homocitrulline a carbamylation derived product in serum and tissues by lc ms ms
    Current protocols in protein science, 2018
    Co-Authors: Stephane Jaisson, Aurore Desmons, Manon Doue, Laetitia Gorisse, Christine Pietrement, Philippe Gillery
    Abstract:

    Carbamylation corresponds to the non-enzymatic binding of isocyanic acid to protein amino groups and participates in protein molecular aging, characterized by the alteration of their structural and functional properties. Carbamylated proteins exert deleterious effects in vivo and are involved in the progression of various diseases, including atherosclerosis and chronic kidney disease. Therefore, there is a growing interest to evaluate the carbamylation rate of blood or tissue proteins, since carbamylation-derived products (CDPs) constitute valuable biomarkers in these contexts. Homocitrulline, formed by isocyanic acid covalently attaches to the e-NH2 group of lysine residue side chain, is the most characteristic CDP. Sensitive and specific quantification of Homocitrulline requires mass spectrometry-based methods. This unit describes a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of Homocitrulline, with special emphasis on pre-analytical steps that allow quantification of total or protein-bound Homocitrulline in serum or tissue samples. © 2018 by John Wiley & Sons, Inc.

  • Homocitrulline as marker of protein carbamylation in hemodialyzed patients
    Clinica Chimica Acta, 2016
    Co-Authors: Stephane Jaisson, Aurore Desmons, Philippe Rieu, Isabelle Kazes, Fouad Fadel, Jeanbaptiste Oudart, Izabella Castilhos Ribeiro Dos Santosweiss, Herve Millart, Fatouma Toure, Philippe Gillery
    Abstract:

    Abstract Background Homocitrulline (HCit) is a carbamylation-derived product (CDP) that has been identified as a valuable biomarker of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of this study was to determine whether initiation of hemodialysis therapy (HD) could induce variations of HCit concentrations in CKD patients. Methods Serum HCit concentrations were determined by LC-MS/MS in CKD patients (n = 108) just before (M0) and six months (M6) after the initiation of HD therapy. Results Mean HCit concentrations reached 1000 μmol/mol Lysine before initiation of HD therapy and decreased by 50% within 6 months after HD onset. HCit concentrations remained stable over time as assessed during a 24-months follow-up period. HCit was mostly found in its protein-bound form in HD patients. HCit concentrations obtained at M0 were positively correlated with urea (r = 0.58) and carbamylated hemoglobin (r = 0.41), and are likely to be promising predictive markers of mortality. However, no correlations were found between HCit concentrations and Kt/V values, suggesting that HCit is not a marker of HD efficiency. Conclusion HCit concentrations reflect the intensity of protein carbamylation and are stable over time during HD treatment, making HCit a reliable biomarker in the follow-up of CKD patients.

  • Homocitrulline a new marker for differentiating acute from chronic renal failure
    Clinical Chemistry and Laboratory Medicine, 2016
    Co-Authors: Aurore Desmons, Stephane Jaisson, Christine Pietrement, Alain Wynckel, Philippe Rieu, Philippe Gillery
    Abstract:

    BACKGROUND Carbamylation is a non-enzymatic post-translational modification of proteins characterized by the addition of isocyanic acid to amino groups. As isocyanic acid mainly originates from the spontaneous dissociation of urea, carbamylation rate is increased during renal failure. The aim of the study was to evaluate serum Homocitrulline (HCit), which results from the carbamylation of e-amino groups of lysine (Lys) residues, in acute renal failure (ARF) and to determine if it could be useful for differentiating acute from chronic renal failure (CRF). METHODS In total, 213 patients with renal failure referred to the nephrology department of the university hospital of Reims were included. Patients were classified into three groups: patients with ARF (ARF group, n=39), patients with CRF complicated with ARF (A/CRF group, n=29) and patients with CRF (CRF group, n=145). Serum HCit concentrations were measured by LC-MS/MS. Concentration kinetics of HCit and urea were studied in patients suffering from ARF. The HCit thresholds distinguishing ARF and CRF were investigated. RESULTS HCit concentrations increased in ARF patients reaching a peak delayed compared to urea concentration peak. HCit concentrations were positively correlated with urea concentrations (r=0.51) and with the time elapsed since the estimated onset of ARF (r=0.57). Serum HCit concentrations were higher (p<0.05) in CRF group compared to ARF group. The receiver operating characteristic curve analysis showed that HCit concentrations <289 μmol/mol Lys were predictive of ARF (Sensitivity: 83%, Specificity: 72%, AUC: 0.856). CONCLUSIONS Our results demonstrate that HCit is a promising biomarker for distinguishing between ARF and CRF patients.

  • increased serum Homocitrulline concentrations are associated with the severity of coronary artery disease
    Clinical Chemistry and Laboratory Medicine, 2015
    Co-Authors: Stephane Jaisson, Izabella Castilhos Ribeiro Dos Santosweiss, Mohsen Kerkeni, Faouzi Addad, Mohammed Hammami, Philippe Gillery
    Abstract:

    BACKGROUND Carbamylation is a non-enzymatic post-translational modification of proteins that has been recently identified as a non-traditional risk factor for atherosclerosis. The aim of this study was to determine whether serum Homocitrulline (HCit), a characteristic carbamylation-derived product, was related to the presence and the severity of coronary artery disease (CAD). METHODS Forty-five control subjects and 109 patients were included in this cross-sectional study. After coronary angiography, the patients were classified as non-CAD patients (patients with normal arteries, n=33) and CAD patients (n=76). The severity of CAD was then evaluated using the Gensini scoring system. Serum total HCit concentrations were determined by LC-MS/MS. RESULTS Serum HCit concentrations were significantly (p<0.001) higher in CAD patients than in control or non-CAD subjects. The receiver operating characteristic curve analysis showed an area under the curve equal to 0.908 (95% confidence interval, 0.853-0.964, p<0.001) and a threshold HCit concentration of 0.16 mmol/mol Lys for predicting the presence of CAD (78.9% sensitivity and 78.8% specificity). HCit concentrations significantly (p<0.001) increased concomitantly with the severity of CAD and were positively correlated with Gensini scores (r=0.725, p<0.001) as well as with the number of stenotic coronary arteries (p<0.001). Furthermore, in a multiple stepwise regression analysis, HCit was significantly (p<0.001) and independently associated with the presence of CAD, the Gensini score, and the number of stenotic arteries (standardized β values of 0.525, 0.722, and 0.642, respectively). CONCLUSIONS Our results demonstrate that serum HCit concentrations are increased during CAD and are positively associated with the severity of the disease.

  • Homocitrulline nouveau marqueur de l insuffisance renale aigue
    Nephrologie & Therapeutique, 2014
    Co-Authors: Aurore Desmons, Stephane Jaisson, Alain Wynckel, Philippe Rieu, Philippe Gillery
    Abstract:

    Introduction La carbamylation est une modification post-traductionnelle non enzymatique correspondant a la fixation irreversible d’acide isocyanique sur les groupements amines des proteines. La principale source endogene d’acide isocyanique etant l’uree, cette reaction est augmentee au cours de l’insuffisance renale. Notre etude a consiste a evaluer le comportement de l’Homocitrulline (HCit), residu d’acide amine resultant de la carbamylation de la lysine (Lys), au cours de l’IRA, et de determiner s’il permettait de differencier IRA et IRC. Patients et methodes Des dosages d’HCit ont ete realises par chromatographie liquide couplee a la spectrometrie de masse en tandem chez 214 patients : 39 en IRA pure (IRA), 30 presentant une IRA surajoutee a l’IRC (IRA/IRC) et 145 en IRC pure (IRC). Des cinetiques d’evolution des concentrations d’uree et d’HCit chez 5 patients atteints d’IRA ont egalement ete realisees. Resultats Les concentrations d’HCit exprimees en μmol/mol de Lys etaient en moyenne de 241,7 (IC 95 % [195,5–287,9], 443,5 (IC 95 % [335,3–551,7]) et 560,5 (IC 95 % [511,7–609,3]) pour les groupes IRA, IRA/IRC, et IRC, respectivement. Ces concentrations etaient significativement plus faibles dans le groupe IRA que dans les groupes IRA/IRC et IRC. Une correlation significative entre la concentration d’HCit et l’uremie a ete retrouvee dans les trois groupes. Une concentration seuil de 300 μmol d’HCit/mol de Lys peut etre proposee pour differencier les patients atteints d’IRA et d’IRC (valeur predictive positive de 91 %). Les cinetiques realisees chez les patients en IRA montrent un decalage dans le temps des concentrations maximales d’HCit et d’uree, avec une concentration maximale d’uree atteinte de facon plus precoce. Discussion et conclusion L’HCit qui, contrairement a l’hemoglobine carbamylee ne subit pas de variations liees a la modification de la duree de vie des hematies, semble constituer un marqueur interessant de differenciation de l’IRA et IRC.