Papers by Anastasios Germenis
BACKGROUND: The consensus documents published to date on hereditary angioedema with C1-inhibitor ... more BACKGROUND: The consensus documents published to date on hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE.
METHODS: During an expert panel meeting that took place during the 9th C1-Inhibitor Deficiency Workshop in Budapest, 2015 [w w w.haenet. hu], pediatric data were presented and discussed and a consensus developed by voting.
RESULTS: The symptoms of C1-INH-HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1-INH-HAE but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1-INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1-INH-HAE family member should be screened for C1-INH deficiency. Pediatric patients should always carry a C1-INH-HAE information card, and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow-up patients in an HAE comprehensive care centre.
CONCLUSIONS: The Pediatric-focused International Consensus for the diagnosis and management of C1-INH-HAE patients was created.
Frontiers in immunology, 2013
Background and Aim:T cell expression of PD1 and inhibition of T effector cells by Foxp3 + -T regu... more Background and Aim:T cell expression of PD1 and inhibition of T effector cells by Foxp3 + -T regulatory cells are among the most powerful mechanisms for achieving a balanced immune response. Our aim was to investigate, how liver FOXP3 and PD1/PDL1 expression is regulated in chronic HBV hepatitis (CHB) on maintained long-term remission in comparison with active disease, and whether they are correlated to the expression of pro-and anti-inflammatory cytokines and apoptosis mediators, along with the degree of histological inflammation and markers of T cell effector restoration.
Archives of Hellenic Medicine
at the end of the article .
Archives of Hellenic Medicine
Äåßêôåò åðéññïÞò (impact factors) ôùí êõñéüôåñùí äéåèíþí ðåñéïäéêþí êáôÜ ãíùóôéêü áíôéêåßìåíï Ìéá... more Äåßêôåò åðéññïÞò (impact factors) ôùí êõñéüôåñùí äéåèíþí ðåñéïäéêþí êáôÜ ãíùóôéêü áíôéêåßìåíï Ìéá ÷ñçóôéêÞ ðñïóÝããéóç 1. Ç ÉÄÅÁ ÊÁÉ Ï ÕÐÏËÏÃÉÓÌÏÓ ÔÏÕ ÄÅÉÊÔÇ ÅÐÉÑÑÏÇÓ Ç ÷ñçóéìïðïßçóç ôùí äçìïóéåõìÝíùí åñåõíçôéêþí áðïôåëåóìÜôùí, üðùò áõôü áðïäåéêíýåôáé áðü ôçí ðá-ñÜèåóç (citation) ôùí áíôßóôïé÷ùí Üñèñùí óôç âéâëéïãñáößá, åß÷å áíáãíùñéóôåß, áðü ðïëý ðáëéÜ, ùò êñé-ôÞñéï ðïéüôçôáò ôçò Ýñåõíáò. Ùò êñéôÞñéï áîéïëüãçóçò ôùí ðåñéïäéêþí, ïé ðáñáèÝóåéò ôùí Üñèñùí ôïõò ÷ñçóé-ìïðïéÞèçêáí, ãéá ðñþôç öïñÜ, ôï 1927, óôçí êëáóéêÞ ìåëÝôç ôùí Gross êáé Gross 1 ãéá ôá ðåñéïäéêÜ ôçò ×çìåßáò, åíþ, óôï ÷þñï ôùí âéïúáôñéêþí ðåñéïäéêþí, ç ðñþôç ðñïóðÜèåéá, ðïõ áíáöåñüôáí óôá ðåñéïäéêÜ Öõóéïëïãßáò, åìöáíßóôçêå ôï 1944. 2 Ç éäÝá åíüò âéâëéïìåôñéêïý äåßêôç, áíåîÜñôçôïõ áðü ôïí üãêï, ôç äéÜñêåéá êáé ôç óõ÷íüôçôá Ýêäïóçò ôùí ðåñéïäéêþí, äéáôõðþèçêå ôï 1955 áðü ôïí Eugene Garfield, éäñõôÞ êáé ôþñá ðéá Åðßôéìï Ðñüåäñï ôïõ Institute for Scientific Information ® (ISI) (www.isinet.com), ìå óôü÷ï ôçí åðéëïãÞ ôùí ðåñéïäéêþí ðïõ èá óõìðåñé-ëáìâÜíïíôáí êáé èá áðïäåëôéþíïíôáí óôç âÜóç äåäï-ìÝíùí (database) ôïõ õðü ßäñõóç éíóôéôïýôïõ. 3 ¸ôóé, óôéò áñ÷Ýò ôçò äåêáåôßáò ôïõ 1960, ìáaeß ìå ôïí Irving H. Sher, o E. Garfield êáôÝëçîå óôç äéáìüñöùóç åíüò äåßêôç, ôïí ïðïßï ïíüìáóå äåßêôç åðéññïÞò (impact factor, IF). Áðü ôüôå êáé ìÝ÷ñé óÞìåñá, ùò IF êÜèå ðåñéïäéêïý ïñßaeåôáé ôï ðçëßêï ôïõ áñéèìïý ôùí ðáñáèÝóåùí üëùí ôùí Üñèñùí ôïõ ôçò ðñïçãïýìåíçò äéåôßáò, ðïõ åìöáíßóôçêáí óôï óýíïëï ôùí ðåñéïäéêþí êáôÜ ôï ðñïçãïýìåíï Ýôïò, äéÜ ôïõ áñéèìïý ôùí Üñèñùí, ðïõ äçìïóéåý-èçêáí óôï óõãêåêñéìÝíï ðåñéïäéêü êáôÜ ôçí ðñïçãïýìåíç äéåôßá. 4 ÄçëáäÞ, ï IF ôïõ ðåñéïäéêïý × ãéá ôï Ýôïò 2003 éóïýôáé ìå ôï ðçëßêï ôïõ áñéèìïý ôùí ðáñáèÝóåùí üëùí ôùí Üñèñùí, ðïõ äçìïóéåýèçêáí ó' áõôü êáôÜ ôá Ýôç 2001 êáé 2002, êáé ïé ïðïßåò åìöáíßóôçêáí êáôÜ ôï Ýôïò 2003 óôá ðåñéïäéêÜ ðïõ êáôáëïãïãñáöïýíôáé áðü ôï ISI, äéÜ ôïõ áñéèìïý ôùí Üñèñùí, ðïõ äçìïóéåýèçêáí óôï ðåñéïäéêü × êáôÜ ôá Ýôç 2001 êáé 2002.
Data in brief, 2015
The quantum state of functional avidity of the synapse formed between a peptide-Major Histocompat... more The quantum state of functional avidity of the synapse formed between a peptide-Major Histocompatibility Complex (pMHC) and a T cell receptor (TCR) is a subject not previously touched upon. Here we present atomic pair correlation meta-data based on crystalized tertiary structures of the Tax (HTLV-1) peptide along with three artificially altered variants, all of which were presented by the (Class I) HLA-A201 protein in complexation with the human (CD8(+)) A6TCR. The meta-data reveal the existence of a direct relationship between pMHC-TCR functional avidity (agonist/antagonist) and peptide pair distribution function (PDF). In this context, antagonist peptides are consistently under-coordinated in respect to Tax. Moreover, Density Functional Theory (DFT) datasets in the BLYP/TZ2P level of theory resulting from relaxation of the H species on peptide tertiary structures reveal that the coordination requirement of agonist peptides is also expressed as a physical observable of the protonat...
International angiology: a journal of the International Union of Angiology
Complement activation in the plasma of patients with severe atherosclerosis (arterial occlusive o... more Complement activation in the plasma of patients with severe atherosclerosis (arterial occlusive or aneurysmatic disease) was investigated in this study. The effects of angiography and reconstructive arterial surgery (RAS) were also assessed. Atherosclerosis was not found to be associated with systemic complement activation. Angiography resulted in high levels of C3 breakdown products. Surgery caused a significant degree of systemic complement activation in both patients with atherosclerosis and controls. Post-operative levels of C3 breakdown products were significantly higher in atheromatic patients than in controls, most likely due to the insertion of dacron arterial prostheses in the first group.
Despite the fact that in Greece it is expected that there are ≈300-500 HAE patients, by 2010 th... more Despite the fact that in Greece it is expected that there are ≈300-500 HAE patients, by 2010 there were only occasional reports of HAE cases. In 2009, the Greek HAE Registry (GHAER) was established under the auspices of the Greek Society of Allergy and Clinical Immunology aiming to ac hieve a baseline epidemiological description, to provide a framework to study the patients' quality of life, to establish a relevant biobank, and to further characterize the disease. 104 patients / 35 families (55% male, 45% female) Age of onset: Median: 8 yrs Lowest: 1st year-of-life (1 case) Highest: 57th year-of-life (1 case)
Journal of Hepatology, 2015
Data in Brief, 2015
The coordination difference between the unprotonated tertiary structures of a native (Tax) peptid... more The coordination difference between the unprotonated tertiary structures of a native (Tax) peptide and a number of its variants - all peptides presented by HLA-A201 and bound to the human A6 T cell receptor-was discovered to constitute a metric of pMHC-TCR functional avidity. Moreover, increasing coordination deviations from the index were found to flag correspondingly weakening immunological outcomes of the variant peptides. The prognostic utility of the coordination difference of unprotonated tertiary structure was established to operate strictly on the peptide scale, seizing to be of relevance either to the immediate peptide environment (i.e. within the realm of peptide short range order, within 7 Å of any peptide atom) or over the entirety of the pMHC-TCR complex. Additionally, the imprint of peptide immunological identity was expressed both by the total coordination as well as by its C-C partial.
at the end of the article Πρωτοπαθείς αντισωματικές ανεπάρκειες στους ενήλικες Σύγχρονη κλινική π... more at the end of the article Πρωτοπαθείς αντισωματικές ανεπάρκειες στους ενήλικες Σύγχρονη κλινική προσέγγιση Οι πρωτοπαθείς αντισωματικές ανεπάρκειες (primary antibody deficiencies, PADs) δεν θεωρούνται πλέον σπάνια νοσήματα. Με τις μισές περίπου από αυτές να διαγιγνώσκονται κατά την ενήλικο ζωή, με μέση καθυστέρηση περί τα 5 έτη και με διάμεση ηλικία θανάτου των ασθενών >50ό έτος της ζωής, αντιπροσωπεύουν ένα κοινό πρόβλημα της Παθολογίας. Το μεγαλύτερο ποσοστό ασθενών με PAD που έχει ανάγκη ιατρικής φροντίδας κατά την ενήλικο ζωή πάσχουν από κοινή ποικίλη ανοσοανεπάρκεια (common variable immunodeficiency, CVID). Στην ανασκόπηση αυτή παρουσιάζονται οι PADs που απαντώνται στους ενήλικες, με ιδιαίτερη έμφαση στις ανεξήγητες μέχρι στιγμής φλεγμονώδεις και λεμφοϋπερπλαστικές εκδηλώσεις της CVID. Οι εν λόγω εκδηλώσεις επικρατούν στην κλινική εικόνα της νόσου, μετά από την αποτελεσματική αντιμετώπιση των λοιμώξεων που επιτεύχθηκε με τη χορήγηση ενδοφλέβιων ανοσοσφαιρινών. Αναφέρονται, επίσης, οι προσπάθειες ταξινόμησης της CVID με βάση τα κλινικά και τα παθοφυσιολογικά χαρακτηριστικά της νόσου. Η σημασία αυτών των ταξινομήσεων και των ανοσοφαινοτυπικών δυνητικών δεικτών που έχουν προσδιοριστεί, αναμένεται να είναι χρήσιμη αναφορικά με την έγκαιρη διάγνωση, ιδιαίτερα στις περιπτώσεις ασθενών που εμφανίζονται με κοκκιωματώδη νόσο ή και λεμφαδενοπάθεια, η κλινική αναγνώριση των οποίων μπορεί να καθυστερήσει σημαντικά. Τέλος, παρουσιάζονται τα κριτήρια και τα διαφορικά διαγνωστικά προβλήματα της CVID στους ενήλικες ασθενείς, καθώς και τα δεδομένα που αφορούν στην αποτελεσματικότητα της θεραπείας υποκατάστασης με την ενδοφλέβια ή υποδόρια χορήγηση ανοσοσφαιρινών, όπως αξιολογούνται 30 χρόνια μετά από την έναρξη της εφαρμογής της.
Data in Brief, 2015
The tertiary structure of the native Cytomegalovirus peptide (NLV) presented by HLA-A2 and bound ... more The tertiary structure of the native Cytomegalovirus peptide (NLV) presented by HLA-A2 and bound to the RA14 T cell receptor was used as a reference for the calculation of atomic coordination differences of both the NLV as well as of a number of singly substituted NLV variants in the absence of TCR. Among the pMHC complexes, the native peptide was found to exhibit the highest total coordination difference in respect to the reference structure, suggesting that it experienced the widest structural adaptation upon recognition by the TCR. In addition, the peptide on the isolated NLV-MHC complex was overcoordinated as compared to the rest of the variants. Moreover, the trend was found to account for a set of measured dissociation constants and critical concentrations for target-cell lysis for all variants in complexation with RA14: functionally, all variant peptides were established to be either weak agonists or null peptides, while, at the same time, our current study established that they were also undercoordinated in respect to NLV. It could, thus, be argued that the most 'efficient' structural adaptation upon pMHC recognition by the TCR requires of the peptide to undergo the widest under-coordination possible. The main structural characteristic which differentiated the NLV in respect to the variants was a the presence of sixteen oxygen atoms (waters) in the former's second coordination shell which accounted for over-coordination of roughly 100% and 30% in the O-O and C-O partials respectively. In fact, in the absence of second shell oxygens, the NLV peptide was decidedly under-coordinated in respect to all of the variants, as also suggested by the C-C partial.
Scandinavian Journal of Haematology, 1986
Immunobiology, 2014
Sepsis and septic shock frequently cause the admission or complicate the clinical course of criti... more Sepsis and septic shock frequently cause the admission or complicate the clinical course of critically ill patients admitted in the intensive care units (ICU). Genetic variations disrupting the immune sensing of infectious organisms, could affect the ability of the immune system to respond to infection, and may influence both the genetic predisposition to infection and the diversity of the clinical presentation of sepsis. The aim of this study was to uncover possible associations between common functional immune gene polymorphisms (of both innate and adaptive immunity) and ICU-acquired sepsis and mortality. The TLR4-D299G (rs4986790), TLR4-T399I (rs4986791), C2-c.841_849+19del28 (rs9332736), TACI-C104R (rs34557412), BAFFR-P21R (rs77874543), and BAFFR-H159Y (rs61756766) polymorphisms were detected in a cohort of 215 critically ill patients, admitted in an 8-bed medical/surgical ICU. Interestingly, TLR4-D299G, TLR4-T399I and BAFFR-P21R carriage was associated with a lower risk of ICU-acquired sepsis. This association applied particularly in medical patients, while in trauma and surgical patients no significant associations were observed. Moreover, carriers of TACI-C104R displayed an undiagnosed mild to moderate hypogammaglobulinemia along with a significantly lower survival rate in the ICU, although lethal events were not attributed to sepsis. These findings further elucidate the role that host immune genetic variations may play in the susceptibility to ICU-acquired sepsis and ICU mortality.
Journal of Autoimmunity, 2015
Aberrant removal of necrotic debris is considered a feature with inflammatory consequences in SLE... more Aberrant removal of necrotic debris is considered a feature with inflammatory consequences in SLE. Herein, primary Sj€ ogren's syndrome (SS) patients were investigated for the first time for the capacity of their sera to degrade secondary necrotic cell remnants (SNEC) and DNA (endonuclease DNase1 activity), as well as for uptake of SNEC by blood-borne phagocytes. For comparison, specimens from unselected SLE and RA patients and from healthy blood donors (HBD) were also studied. Compared to HBD, the sera from SS and SLE patients studied (but not RA) were found to exhibit significantly impaired capacity for degradation of SNEC (both for p ¼ 0.007) and deficient DNase1 activity (both for p < 0.0001). The deficient DNase1 activity in SS and SLE sera did not owe to decreased DNase1 protein levels. It correlated inversely with increased serum levels of circulating nucleosomes and cell-free DNA (p < 0.0001), as well as with the disease activity indices of SS (r ¼ À0.445, p ¼ 0.0001) and SLE (r ¼ À0.500, p ¼ 0.013). In exvivo whole blood analyses, SS and SLE patients (but not RA) also manifested significantly increased SNECphagocytosis by monocytes and granulocytes (all for p < 0.0001) that also correlated with disease severity indices of SS (p ¼ 0.001) and SLE (p ¼ 0.01). In various cross-admixture experiments, such aberration was found to reside in the hyperfunctional activity of phagocytes, the impaired degrading activity of serum DNase1 and the SNEC-binding capacity of serum IgG of SS and SLE patients. The sera of SS and SLE patients (but not of RA) induced significant SNEC-phagocytosis by healthy monocytes that correlated inversely with the DNase1 activity (r ¼ À0.634, p < 0.0001) of these sera. In line with this, the inhibition of DNase1 in HBD sera by G-actin was found to lead to significantly diminished SNEC degradation and increased SNEC uptake by healthy phagocytes (p ¼ 0.0009), supporting the important physiologic role of serum DNase1 in the prevention of SNEC-phagocytosis. Purified serum IgG preparations from SS and SLE patients manifested increased binding to SNEC and were able to enhance significantly the engulfment of SNEC by healthy phagocytes both directly (under serum-free conditions, p 0.009) and via the prevention of physiologic degradation of SNEC by serum, most likely due to their "shielding" against endonuclease digestion (p ¼ 0.0005). These data indicate that upon cell necrosis, the immune system of SS and SLE patients may be overly exposed to the necrotic debris, a fact that probably holds a key role in the pathogenesis of inflammatory and autoimmune reactions observed in these disorders.
Vox Sanguinis, 1982
Determination of the genetically controlled variants of the C3 system has been accomplished by el... more Determination of the genetically controlled variants of the C3 system has been accomplished by electrophoresis on cellulose acetate membrane followed by immunofixation with a specific anti-C3 antiserum. The results have been confirmed with the use of reference sera and compared with those obtained from conventional high voltage agarose gel electrophoresis. The interference of some electrophoretic variables on the technique has been investigated. The method is rapid, accurate, reliable and gives good separation of at least the three common C3 phenotypes.
Hellenic Journal of Surgery, 2010
Objective: This study was scheduled in an attempt to detect the complement activation following a... more Objective: This study was scheduled in an attempt to detect the complement activation following abdominal operations of medium severity with uneventful postoperative course, and the possible effect of gallstones in bile complement. Method: Seventeen patients with cholelithiasis (mean age 58.1 years) were studied after undergoing elective open cholecystectomy. Blood samples were obtained before and immediately after the operation as well as on postoperative days 1, 2, 4 and 5. Complement activation was also measured in bile collected intraoperatively from ten patients (mean age 63.7 years range 47-79) submitted to elective cholecystectomy for cholelithiasis. Bile was also collected intraoperatively from ten other patients (mean age 66.2 years, range 51-78) who were operated electively for benign disease. This bile was incubated with gallstones and complement activation was measured before, immediately after, and at the 30min, 1h and 2h of incubation. Twenty-seven apparently healthy individuals (mean age 41.9 years) were used as controls. Results: (a) Among the complement activation products, only C4d presented a statistically significant postoperative variation (p<0.005) with a peak value between the 1st and 4th postoperative day. (b) C3adesArg and SC5b-9 concentrations were significantly higher in all samples than those of the controls. (c) C3 and C4 levels varied in accordance with the postoperative acute phase reaction as reflected by the CRP values. (d) The levels of all activation products measured in the bile of patients with cholelithiasis were significantly higher than those detected in the bile of patients with benign disease (p<0.005). (e) There was also a great increase in the levels of these products in the bile incubated with gallstones. Conclusions: The uneventful postoperative course following abdominal operations of medium severity is accompanied by a low level activation of the classical complement pathway, and the above results indicate that the presence of gallstones may activate serum complement system directly. Gallstones cause activation of bile complement in vivo. Furthermore, they cause an in vitro activation of bile complement. The in vivo activation of bile complement in the presence of gallstones indicates that they exert a direct effect on the final evolution of the in situ processes
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Papers by Anastasios Germenis
METHODS: During an expert panel meeting that took place during the 9th C1-Inhibitor Deficiency Workshop in Budapest, 2015 [w w w.haenet. hu], pediatric data were presented and discussed and a consensus developed by voting.
RESULTS: The symptoms of C1-INH-HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1-INH-HAE but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1-INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1-INH-HAE family member should be screened for C1-INH deficiency. Pediatric patients should always carry a C1-INH-HAE information card, and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow-up patients in an HAE comprehensive care centre.
CONCLUSIONS: The Pediatric-focused International Consensus for the diagnosis and management of C1-INH-HAE patients was created.
METHODS: During an expert panel meeting that took place during the 9th C1-Inhibitor Deficiency Workshop in Budapest, 2015 [w w w.haenet. hu], pediatric data were presented and discussed and a consensus developed by voting.
RESULTS: The symptoms of C1-INH-HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1-INH-HAE but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1-INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1-INH-HAE family member should be screened for C1-INH deficiency. Pediatric patients should always carry a C1-INH-HAE information card, and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow-up patients in an HAE comprehensive care centre.
CONCLUSIONS: The Pediatric-focused International Consensus for the diagnosis and management of C1-INH-HAE patients was created.