Lilian Varga - Academia.edu (original) (raw)

Papers by Lilian Varga

Research paper thumbnail of Are these patients indeed resistant to treatment with C1 inhibitor concentrate?

British Journal of Dermatology, 2012

Research paper thumbnail of C1r-C1s-C1inhibitor (C1rs-C1inh) complex measurements in tears of patients before and after penetrating keratoplasty

Current Eye Research

The aim of this pilot study was to determine the presence of complement activation products in te... more The aim of this pilot study was to determine the presence of complement activation products in tears from pre- and postkeratoplasty eyes and the fellow eyes in order to investigate the activation of the classical and alternative pathways of the complement system in the early postkeratoplasty period. Tear samples from both eyes of 19 prekeratoplasty patients were tested. From 10 patients, samples were taken before operation, one week and 3 weeks after penetrating keratoplasty. Only baseline and 1 weak samples, and baseline and 3 week samples were available from 5 and 2 patients, respectively, while only baseline tear samples were collected from 2 patients. Tear concentration of two complement activation products, C1rs-C1inh and C3bBbP were determined by enzyme-linked immunosorbent assay. There was no difference (p = 0.339) between baseline samples of the eyes waiting for operation (0.93 +/- 0.51 AU/ml, mean +/- SEM) and the fellow eyes (0.33 +/- 0.33 AU/ml) in respect of mean C1rs-C1inh complex concentration. The one-week samples of the operated eyes revealed significantly (p = 0.006) elevated levels of C1rs-C1inh complexes (18.8. +/- 6.37 AU/ml), compared to their baseline samples (1.18 +/- 0.64 AU/ml), whereas the one-week values of the fellow eyes did not differ from the baseline values. Compared to the increased one-week values, the three-week values decreased to the baseline values in the operated eyes. C3bBbP could be detected in 3/68 tear samples. In our study we demonstrated the increased concentration of C1rs-C1inh complex in several tear samples taken early after human penetrating keratoplasty. These findings provide direct evidence that the classical pathway of complement may be activated in the early postoperative period after penetrating keratoplasty.

Research paper thumbnail of Humán és bakteriális hősokkfehérjék komplementaktiváló képességének összehasonlító vizsgálata = Study on the complement activating ability of human and bacterial heat-shock proteins

A kutatási periódusban 4 célkitűzésben vizsgáltuk humán és bakteriális hősokkfehérjék komplementa... more A kutatási periódusban 4 célkitűzésben vizsgáltuk humán és bakteriális hősokkfehérjék komplementaktiváló képességét. A komplementaktiváció legfontosabb regulátorainak, a Hsp60/65 ellens antitestek vonatkozásában azt kaptuk, hogy jelentős reguláló tényező az IL-6 promóter -174-es polimorfizmusa. Kimutattuk továbbá, hogy az anti-Hsp60 autoantitestek a természetes autoantitest repertoárba tartoznak, valamint epitóp szinten is elkülöníthetők a az anti-Hsp65 antitestektől. Eredményeink jelentőségét az adja, hogy eddig csak korlátozott ismeretanyaggal rendelkeztünk az anti-Hsp autoantitestek összefüggéseire és regulációjára vonatkozóan. A pályázat támogatásával az erre vonatkozó részletes immunológiai ismeretanyag gazdagodott. A Hsp70 komplementaktiváló képességének in vitro vizsgálatát megnehezítette a rekombináns fehérjék endotoxin szennyezettsége, ami mellett nem tudtuk megítélni a komplementaktiváció pontos mechanizmusát. A Hsp70 további vizsgálatát in vivo, klinikai beteganyagon való...

Research paper thumbnail of The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema

Journal of immunology (Baltimore, Md. : 1950), Jan 14, 2015

C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine protea... more C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patient...

Research paper thumbnail of Complexes between the lectin pathway serine protease MASP-1 and C1 inhibitor are associated with severity of Hereditary Angioedema

Research paper thumbnail of Erratum to: Human Plasma-Derived, Nanofiltered C1-Inhibitor Concentrate (Cinryze®), a Novel Therapeutic Alternative for the Management of Hereditary Angioedema Resulting From C1-Inhibitor Deficiency

Biologics in Therapy, 2012

The authors of the above-mentioned paper noticed a few errors in the text, as reported. In the 'P... more The authors of the above-mentioned paper noticed a few errors in the text, as reported. In the 'Pharmacokinetics' section, with regards to the C1 inhibitor, Cinryze ® (ViroPharma Inc.), the maximum plasma concentration (C max ) (units/mL) values should read 0.68 ± 0.08 (n = 12) versus 0.85 ± 0.12 (n = 13), and not 0.68 ± 0.08 (n = 12) versus 0.33 ± 0.20 (n = 12), as reported. The authors regret this error, and thank Springer Healthcare for publishing the correction.

Research paper thumbnail of High normal serum levels of C3 and C1 inhibitor, two acute-phase proteins belonging to the complement system, occur more frequently in patients with Crohn's disease than ulcerative colitis

Digestive diseases and sciences, 2003

Few data are available on measurements of serum concentrations of complement proteins in inflamma... more Few data are available on measurements of serum concentrations of complement proteins in inflammatory bowel disease (IBD). Therefore we measured serum levels of C3, C4, and C1-esterase inhibitor (C1-INH) as well as C-reactive protein (CRP) in 167 patients with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). Median serum concentrations of C3 and C1-INH were significantly higher in CD than in UC. According to multiple logistic regression analysis adjusted to age, sex, activity of disease, and presence of extraintestinal manifestations, IBD patients with high-normal (> or = 128%, > or = 75th percentile ) C1-INH concentrations had significantly (0.0275) higher odds ratio to have a diagnosis of CD than UC. Patients with high-normal C3 (> or = 1.40 g/liter) and high (> or =20 mg/liter) CRP concentrations had an even higher odds ratio of a CD diagnosis (P = 0.0132). Our findings indicate that measurement of C3, C1-INH, and CRP can be used as an additiona...

Research paper thumbnail of Attacks of hereditary angioedema (HAE) treated with icatibant in the open-label phase of the fast-2 study

World Allergy Organization Journal, 2007

Research paper thumbnail of A középkorú lakosság morbiditásának és mortalitásának összefüggése az MHC centrális régiójában található egyes génvariánsokkal és haplotipusokkal = Relationship between the morbidity and mortality of the middle-age people with some gene variants and haplotypes in the central region of MHC

A projekt keretében -korábbi adataink utánvizsgálat céljából - a középkorú lakosság morbiditásána... more A projekt keretében -korábbi adataink utánvizsgálat céljából - a középkorú lakosság morbiditásának és mortalitásának összefüggéseit tanulmányoztuk az MHC centrális régiójában található egyes génvariánsokkal és haplotipusokkal. Fontosabb új eredményeink: 1. Új módszert dolgoztunk ki a C4A és C4B gének kópiaszámának meghatározására 2. A C4B*Q0 (a C4B gén alacsony kópia száma) és a fokozott cardiovascularis morbiditás és mortalitás között kapcsolatot sikerült megerősítenünk az új genotipizálási módszer segítségével, 3. Elsőként sikerült feltérképezni az ősi kiterjesztett MHC haplotípusok előfordulását a magyar populációban és bizonyítottuk, hogy a leggyakoribb, 8.1 j. ősi haplotípus hordozóinak colorectalis carcinoma kockázata lényegesen nagyobb, mint a nem-hordozóké. 4. A C4B*Q0 genotípus és a fokozott cardiovascularis morbiditás és mortalitás között összefüggés egyik lehetséges magyarázata az, hogy a 21-hidroxiláz enzimet kódoló CYP-21 gén funkcionális rendellenessége és a C4A/C4B gé...

Research paper thumbnail of Special Issue: 12th European Meeting on Complement in Human Disease, Visegrad, September 5-8, 2009 Introduction

Research paper thumbnail of Early complement activation follows eversion carotid endarterectomy and correlates with the time of clamping of the carotid artery

Molecular Immunology, 2008

Complement activation plays an important role in ischemia/reperfusion (I/R) injury. The objective... more Complement activation plays an important role in ischemia/reperfusion (I/R) injury. The objective of the present study was to detect the presence and mechanism of complement activation in patients who underwent carotid endarterectomy (CEA). Complement activation products C1rsC1-inhibitor, C4d, C3a and SC5b-9 and concentrations of C-reactive protein (CRP) were measured in samples serially taken from 16 patients with eversion CEA and 10 with carotid artery stenting (CAS) in the first 24h post-surgery/intervention. MBL2 genotypes were also determined. In patients with CEA an intense increase in C3a levels were observed immediately after surgery (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), accompanied by a slight elevation in SC5b-9 levels (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). C3a levels remained elevated until 4h post-surgery, compared with the baseline values and with CAS patients. Peak C3a levels correlated with the time of carotid clamping (r=0.5921, p=0.02). No significant changes were detected in C1rsC1-inhibitor or C4d levels following CEA, and we found no association between the generation of C3a and MBL2 genotypes or CRP levels. Complement activation was not present in patients with CAS. Early complement activation follows CEA and correlates with the time of I/R injury. The lack of C4d generation suggests the role of the alternative and not the lectin pathway in the process.

Research paper thumbnail of Role of Complement in Allergy

The Complement System, 2004

ABSTRACT For several decades the role for complement as a mediator of type I hypersensitivity rea... more ABSTRACT For several decades the role for complement as a mediator of type I hypersensitivity reaction was not considered important. In the last ten years, however, the role of complement in allergy and asthma has been revisited and revised. This chapter summarizes the recent results on this topic. In in vitro and animal experiments several findings on the role of complement activation in both the sensitization and effector phases of allergic reactions have been published. Association between allergy-induced provocation of airway symptoms and generation of complement activation products was demonstrated in patients as well. Our group studied the mechanism of complement activation by allergens, and revealed a strong correlation between the extent of in vitro activation by ragweed allergen and the severity of clinical symptoms in the ragweed season in the same allergic patients. The results of most experiments described in the chapter have therapeutic relevance; clinical trials are expected to be started in the near future.

Research paper thumbnail of The level of C1rC1sC1inh complexes is elevated in hereditary angioedema and correlates with disease severity

Molecular Immunology, 2008

Research paper thumbnail of Early complement activation is associated with unfavorable outcomes in acute ischaemic stroke

Molecular Immunology, 2008

Research paper thumbnail of Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema

European Journal of Gastroenterology & Hepatology, 2001

Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of t... more Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of the disease can mimic surgical emergencies, prompt and accurate diagnosis is essential. This study was undertaken to evaluate the usefulness of serial abdominal ultrasound (US) examinations. Seventy patients with HAE were followed up for almost a decade. All patients presenting with an acute oedematous attack underwent abdominal US, which was then repeated 24 and 48 h after appropriate therapy. Twenty-two acute oedematous attacks with abdominal complaints severe enough to justify hospital admission occurred in the study population. Abdominal US performed during the attack showed oedematous thickening of the intestinal wall in 80% of cases and invariably demonstrated the presence of free peritoneal fluid in all patients. Rapid symptomatic relief achieved by treatment was accompanied by the significant regression of US abnormalities. Transitory ascites demonstrated by abdominal US is a clue to the diagnosis of an acute abdominal attack of HAE. The possibility of HAE should always be considered whenever unexplained abdominal pain recurs with or without ascites.

Research paper thumbnail of Frequency of the virilising effects of attenuated androgens reported by women with hereditary angioedema

Orphanet Journal of Rare Diseases, 2014

Background: Danazol, a drug extensively used in the management of hereditary angioedema due to C1... more Background: Danazol, a drug extensively used in the management of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), has various side effects. This study investigated the virilizing actions of this drug in 31 danazol-treated female patients with HAE-C1-INH. We compared our findings with those of healthy controls and with literature data.

Research paper thumbnail of Plasma-Derived C1 Inhibitor Concentrate Did Not Increase the Risk of Thromboembolism in Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency – a Long-Term Survey

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Successful prophylaxis with recombinant human C1 inhibitor in a patient with hereditary angioedema

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2015

Research paper thumbnail of Dancing with Complement C4 and the RP-C4-CYP21-TNX (RCCX) Modules of the Major Histocompatibility Complex

Progress in Nucleic Acid Research and Molecular Biology, 2003

The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among diff... more The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among different human individuals. Three quarters of the C4 genes in Caucasian populations have the endogenous retrovirus, HERV-K(C4), in the ninth intron. The remainder does not. The C4 serum proteins are highly polymorphic and their concentrations vary from 100 to approximately 1000 microg/ml. There are two distinct classes of C4 protein, C4A and C4B, which have diversified to fulfill (a) the opsonization/immunoclearance purposes and (b) the well-known complement function in the killing of microbes by lysis and neutralization, respectively. Many infectious and autoimmune diseases are associated with complete or partial deficiency of C4A and/or C4B. The adverse effects of high C4 gene dosages, however, are just emerging, as the concepts of human C4 genetics are revised and accurate techniques are applied to distinguish partial deficiencies from differential expression caused by unequal C4A and C4B gene dosages and gene sizes. This review attempts to dissect the sophisticated genetics of complement C4A and C4B. The emphases are on the qualitative and quantitative diversities of C4 genotypes and phenotypes. The many allotypic variants and the processed products of human and mouse C4 proteins are described. The modular variation of C4 genes together with the serine/threonine nuclear kinase gene RP, the steroid 21-hydroxylase CYP21, and extracellular matrix protein TNX (RCCX modules) are investigated for the effects on homogenization of C4 protein polymorphisms, and on the unequal genetic crossovers that knocked out the functions of CYP21 and/or TNX. Furthermore, the influence of the endogenous retrovirus HERV-K(C4) on C4 gene expression and the dispersal of HERV-K(C4) family members in the human genome are discussed.

Research paper thumbnail of Home treatment of attacks with conestat alfa in hereditary angioedema due to C1-inhibitor deficiency

Allergy and Asthma Proceedings, 2014

Conestat alfa, a recombinant human C1 inhibitor (rhC1-INH) is a novel therapeutic option for the ... more Conestat alfa, a recombinant human C1 inhibitor (rhC1-INH) is a novel therapeutic option for the acute treatment of hereditary angioedema due to C1-INH (HAE-C1-INH) deficiency. Our aim was to investigate the efficacy and safety profile of conestat alfa in patients with HAE-C1-INH, under real-life conditions. We analyzed 65 edematous episodes requiring acute treatment and occurring in two female HAE-C1-INH patients. The patients were treated at home with rhC1-INH per occasion. They recorded the time of rhC1-INH administration, the time to the onset of improvement, and time to the complete resolution of symptoms, as well as the side effects. Symptom severity and patient satisfaction were measured with a visual analog scale (VAS). Thirty-three HAE attacks occurred in submucosal tissue, 17 in subcutaneous tissue, and 15 had mixed locations. After the administration of rhC1-INH, clinical symptoms improved within 0.50 (0.17-4.50 hours) hours and resolved completely within 9.00 (1.67-58.75 hours) hours. The time between the onset of the attack and the administration of rhC1-INH was correlated with the time when the symptoms stopped worsening (R = 0.3212; p = 0.0096) and the time to complete resolution of the symptoms (R = 0.4774; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). The time to response to the drug differed with attack location. The efficacy and safety of rhC1-INH persisted after repeated use. None of the patients experienced a recurrence of the HAE attack or drug-related systemic adverse events. The mean VAS score of patient satisfaction was 93.14. Home treatment with rhC1-INH was an effective and well-tolerated therapy for all types of HAE attacks.

Research paper thumbnail of Are these patients indeed resistant to treatment with C1 inhibitor concentrate?

British Journal of Dermatology, 2012

Research paper thumbnail of C1r-C1s-C1inhibitor (C1rs-C1inh) complex measurements in tears of patients before and after penetrating keratoplasty

Current Eye Research

The aim of this pilot study was to determine the presence of complement activation products in te... more The aim of this pilot study was to determine the presence of complement activation products in tears from pre- and postkeratoplasty eyes and the fellow eyes in order to investigate the activation of the classical and alternative pathways of the complement system in the early postkeratoplasty period. Tear samples from both eyes of 19 prekeratoplasty patients were tested. From 10 patients, samples were taken before operation, one week and 3 weeks after penetrating keratoplasty. Only baseline and 1 weak samples, and baseline and 3 week samples were available from 5 and 2 patients, respectively, while only baseline tear samples were collected from 2 patients. Tear concentration of two complement activation products, C1rs-C1inh and C3bBbP were determined by enzyme-linked immunosorbent assay. There was no difference (p = 0.339) between baseline samples of the eyes waiting for operation (0.93 +/- 0.51 AU/ml, mean +/- SEM) and the fellow eyes (0.33 +/- 0.33 AU/ml) in respect of mean C1rs-C1inh complex concentration. The one-week samples of the operated eyes revealed significantly (p = 0.006) elevated levels of C1rs-C1inh complexes (18.8. +/- 6.37 AU/ml), compared to their baseline samples (1.18 +/- 0.64 AU/ml), whereas the one-week values of the fellow eyes did not differ from the baseline values. Compared to the increased one-week values, the three-week values decreased to the baseline values in the operated eyes. C3bBbP could be detected in 3/68 tear samples. In our study we demonstrated the increased concentration of C1rs-C1inh complex in several tear samples taken early after human penetrating keratoplasty. These findings provide direct evidence that the classical pathway of complement may be activated in the early postoperative period after penetrating keratoplasty.

Research paper thumbnail of Humán és bakteriális hősokkfehérjék komplementaktiváló képességének összehasonlító vizsgálata = Study on the complement activating ability of human and bacterial heat-shock proteins

A kutatási periódusban 4 célkitűzésben vizsgáltuk humán és bakteriális hősokkfehérjék komplementa... more A kutatási periódusban 4 célkitűzésben vizsgáltuk humán és bakteriális hősokkfehérjék komplementaktiváló képességét. A komplementaktiváció legfontosabb regulátorainak, a Hsp60/65 ellens antitestek vonatkozásában azt kaptuk, hogy jelentős reguláló tényező az IL-6 promóter -174-es polimorfizmusa. Kimutattuk továbbá, hogy az anti-Hsp60 autoantitestek a természetes autoantitest repertoárba tartoznak, valamint epitóp szinten is elkülöníthetők a az anti-Hsp65 antitestektől. Eredményeink jelentőségét az adja, hogy eddig csak korlátozott ismeretanyaggal rendelkeztünk az anti-Hsp autoantitestek összefüggéseire és regulációjára vonatkozóan. A pályázat támogatásával az erre vonatkozó részletes immunológiai ismeretanyag gazdagodott. A Hsp70 komplementaktiváló képességének in vitro vizsgálatát megnehezítette a rekombináns fehérjék endotoxin szennyezettsége, ami mellett nem tudtuk megítélni a komplementaktiváció pontos mechanizmusát. A Hsp70 további vizsgálatát in vivo, klinikai beteganyagon való...

Research paper thumbnail of The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema

Journal of immunology (Baltimore, Md. : 1950), Jan 14, 2015

C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine protea... more C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patient...

Research paper thumbnail of Complexes between the lectin pathway serine protease MASP-1 and C1 inhibitor are associated with severity of Hereditary Angioedema

Research paper thumbnail of Erratum to: Human Plasma-Derived, Nanofiltered C1-Inhibitor Concentrate (Cinryze®), a Novel Therapeutic Alternative for the Management of Hereditary Angioedema Resulting From C1-Inhibitor Deficiency

Biologics in Therapy, 2012

The authors of the above-mentioned paper noticed a few errors in the text, as reported. In the 'P... more The authors of the above-mentioned paper noticed a few errors in the text, as reported. In the 'Pharmacokinetics' section, with regards to the C1 inhibitor, Cinryze ® (ViroPharma Inc.), the maximum plasma concentration (C max ) (units/mL) values should read 0.68 ± 0.08 (n = 12) versus 0.85 ± 0.12 (n = 13), and not 0.68 ± 0.08 (n = 12) versus 0.33 ± 0.20 (n = 12), as reported. The authors regret this error, and thank Springer Healthcare for publishing the correction.

Research paper thumbnail of High normal serum levels of C3 and C1 inhibitor, two acute-phase proteins belonging to the complement system, occur more frequently in patients with Crohn's disease than ulcerative colitis

Digestive diseases and sciences, 2003

Few data are available on measurements of serum concentrations of complement proteins in inflamma... more Few data are available on measurements of serum concentrations of complement proteins in inflammatory bowel disease (IBD). Therefore we measured serum levels of C3, C4, and C1-esterase inhibitor (C1-INH) as well as C-reactive protein (CRP) in 167 patients with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). Median serum concentrations of C3 and C1-INH were significantly higher in CD than in UC. According to multiple logistic regression analysis adjusted to age, sex, activity of disease, and presence of extraintestinal manifestations, IBD patients with high-normal (> or = 128%, > or = 75th percentile ) C1-INH concentrations had significantly (0.0275) higher odds ratio to have a diagnosis of CD than UC. Patients with high-normal C3 (> or = 1.40 g/liter) and high (> or =20 mg/liter) CRP concentrations had an even higher odds ratio of a CD diagnosis (P = 0.0132). Our findings indicate that measurement of C3, C1-INH, and CRP can be used as an additiona...

Research paper thumbnail of Attacks of hereditary angioedema (HAE) treated with icatibant in the open-label phase of the fast-2 study

World Allergy Organization Journal, 2007

Research paper thumbnail of A középkorú lakosság morbiditásának és mortalitásának összefüggése az MHC centrális régiójában található egyes génvariánsokkal és haplotipusokkal = Relationship between the morbidity and mortality of the middle-age people with some gene variants and haplotypes in the central region of MHC

A projekt keretében -korábbi adataink utánvizsgálat céljából - a középkorú lakosság morbiditásána... more A projekt keretében -korábbi adataink utánvizsgálat céljából - a középkorú lakosság morbiditásának és mortalitásának összefüggéseit tanulmányoztuk az MHC centrális régiójában található egyes génvariánsokkal és haplotipusokkal. Fontosabb új eredményeink: 1. Új módszert dolgoztunk ki a C4A és C4B gének kópiaszámának meghatározására 2. A C4B*Q0 (a C4B gén alacsony kópia száma) és a fokozott cardiovascularis morbiditás és mortalitás között kapcsolatot sikerült megerősítenünk az új genotipizálási módszer segítségével, 3. Elsőként sikerült feltérképezni az ősi kiterjesztett MHC haplotípusok előfordulását a magyar populációban és bizonyítottuk, hogy a leggyakoribb, 8.1 j. ősi haplotípus hordozóinak colorectalis carcinoma kockázata lényegesen nagyobb, mint a nem-hordozóké. 4. A C4B*Q0 genotípus és a fokozott cardiovascularis morbiditás és mortalitás között összefüggés egyik lehetséges magyarázata az, hogy a 21-hidroxiláz enzimet kódoló CYP-21 gén funkcionális rendellenessége és a C4A/C4B gé...

Research paper thumbnail of Special Issue: 12th European Meeting on Complement in Human Disease, Visegrad, September 5-8, 2009 Introduction

Research paper thumbnail of Early complement activation follows eversion carotid endarterectomy and correlates with the time of clamping of the carotid artery

Molecular Immunology, 2008

Complement activation plays an important role in ischemia/reperfusion (I/R) injury. The objective... more Complement activation plays an important role in ischemia/reperfusion (I/R) injury. The objective of the present study was to detect the presence and mechanism of complement activation in patients who underwent carotid endarterectomy (CEA). Complement activation products C1rsC1-inhibitor, C4d, C3a and SC5b-9 and concentrations of C-reactive protein (CRP) were measured in samples serially taken from 16 patients with eversion CEA and 10 with carotid artery stenting (CAS) in the first 24h post-surgery/intervention. MBL2 genotypes were also determined. In patients with CEA an intense increase in C3a levels were observed immediately after surgery (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), accompanied by a slight elevation in SC5b-9 levels (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). C3a levels remained elevated until 4h post-surgery, compared with the baseline values and with CAS patients. Peak C3a levels correlated with the time of carotid clamping (r=0.5921, p=0.02). No significant changes were detected in C1rsC1-inhibitor or C4d levels following CEA, and we found no association between the generation of C3a and MBL2 genotypes or CRP levels. Complement activation was not present in patients with CAS. Early complement activation follows CEA and correlates with the time of I/R injury. The lack of C4d generation suggests the role of the alternative and not the lectin pathway in the process.

Research paper thumbnail of Role of Complement in Allergy

The Complement System, 2004

ABSTRACT For several decades the role for complement as a mediator of type I hypersensitivity rea... more ABSTRACT For several decades the role for complement as a mediator of type I hypersensitivity reaction was not considered important. In the last ten years, however, the role of complement in allergy and asthma has been revisited and revised. This chapter summarizes the recent results on this topic. In in vitro and animal experiments several findings on the role of complement activation in both the sensitization and effector phases of allergic reactions have been published. Association between allergy-induced provocation of airway symptoms and generation of complement activation products was demonstrated in patients as well. Our group studied the mechanism of complement activation by allergens, and revealed a strong correlation between the extent of in vitro activation by ragweed allergen and the severity of clinical symptoms in the ragweed season in the same allergic patients. The results of most experiments described in the chapter have therapeutic relevance; clinical trials are expected to be started in the near future.

Research paper thumbnail of The level of C1rC1sC1inh complexes is elevated in hereditary angioedema and correlates with disease severity

Molecular Immunology, 2008

Research paper thumbnail of Early complement activation is associated with unfavorable outcomes in acute ischaemic stroke

Molecular Immunology, 2008

Research paper thumbnail of Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema

European Journal of Gastroenterology & Hepatology, 2001

Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of t... more Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of the disease can mimic surgical emergencies, prompt and accurate diagnosis is essential. This study was undertaken to evaluate the usefulness of serial abdominal ultrasound (US) examinations. Seventy patients with HAE were followed up for almost a decade. All patients presenting with an acute oedematous attack underwent abdominal US, which was then repeated 24 and 48 h after appropriate therapy. Twenty-two acute oedematous attacks with abdominal complaints severe enough to justify hospital admission occurred in the study population. Abdominal US performed during the attack showed oedematous thickening of the intestinal wall in 80% of cases and invariably demonstrated the presence of free peritoneal fluid in all patients. Rapid symptomatic relief achieved by treatment was accompanied by the significant regression of US abnormalities. Transitory ascites demonstrated by abdominal US is a clue to the diagnosis of an acute abdominal attack of HAE. The possibility of HAE should always be considered whenever unexplained abdominal pain recurs with or without ascites.

Research paper thumbnail of Frequency of the virilising effects of attenuated androgens reported by women with hereditary angioedema

Orphanet Journal of Rare Diseases, 2014

Background: Danazol, a drug extensively used in the management of hereditary angioedema due to C1... more Background: Danazol, a drug extensively used in the management of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), has various side effects. This study investigated the virilizing actions of this drug in 31 danazol-treated female patients with HAE-C1-INH. We compared our findings with those of healthy controls and with literature data.

Research paper thumbnail of Plasma-Derived C1 Inhibitor Concentrate Did Not Increase the Risk of Thromboembolism in Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency – a Long-Term Survey

Journal of Allergy and Clinical Immunology, 2015

Research paper thumbnail of Successful prophylaxis with recombinant human C1 inhibitor in a patient with hereditary angioedema

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2015

Research paper thumbnail of Dancing with Complement C4 and the RP-C4-CYP21-TNX (RCCX) Modules of the Major Histocompatibility Complex

Progress in Nucleic Acid Research and Molecular Biology, 2003

The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among diff... more The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among different human individuals. Three quarters of the C4 genes in Caucasian populations have the endogenous retrovirus, HERV-K(C4), in the ninth intron. The remainder does not. The C4 serum proteins are highly polymorphic and their concentrations vary from 100 to approximately 1000 microg/ml. There are two distinct classes of C4 protein, C4A and C4B, which have diversified to fulfill (a) the opsonization/immunoclearance purposes and (b) the well-known complement function in the killing of microbes by lysis and neutralization, respectively. Many infectious and autoimmune diseases are associated with complete or partial deficiency of C4A and/or C4B. The adverse effects of high C4 gene dosages, however, are just emerging, as the concepts of human C4 genetics are revised and accurate techniques are applied to distinguish partial deficiencies from differential expression caused by unequal C4A and C4B gene dosages and gene sizes. This review attempts to dissect the sophisticated genetics of complement C4A and C4B. The emphases are on the qualitative and quantitative diversities of C4 genotypes and phenotypes. The many allotypic variants and the processed products of human and mouse C4 proteins are described. The modular variation of C4 genes together with the serine/threonine nuclear kinase gene RP, the steroid 21-hydroxylase CYP21, and extracellular matrix protein TNX (RCCX modules) are investigated for the effects on homogenization of C4 protein polymorphisms, and on the unequal genetic crossovers that knocked out the functions of CYP21 and/or TNX. Furthermore, the influence of the endogenous retrovirus HERV-K(C4) on C4 gene expression and the dispersal of HERV-K(C4) family members in the human genome are discussed.

Research paper thumbnail of Home treatment of attacks with conestat alfa in hereditary angioedema due to C1-inhibitor deficiency

Allergy and Asthma Proceedings, 2014

Conestat alfa, a recombinant human C1 inhibitor (rhC1-INH) is a novel therapeutic option for the ... more Conestat alfa, a recombinant human C1 inhibitor (rhC1-INH) is a novel therapeutic option for the acute treatment of hereditary angioedema due to C1-INH (HAE-C1-INH) deficiency. Our aim was to investigate the efficacy and safety profile of conestat alfa in patients with HAE-C1-INH, under real-life conditions. We analyzed 65 edematous episodes requiring acute treatment and occurring in two female HAE-C1-INH patients. The patients were treated at home with rhC1-INH per occasion. They recorded the time of rhC1-INH administration, the time to the onset of improvement, and time to the complete resolution of symptoms, as well as the side effects. Symptom severity and patient satisfaction were measured with a visual analog scale (VAS). Thirty-three HAE attacks occurred in submucosal tissue, 17 in subcutaneous tissue, and 15 had mixed locations. After the administration of rhC1-INH, clinical symptoms improved within 0.50 (0.17-4.50 hours) hours and resolved completely within 9.00 (1.67-58.75 hours) hours. The time between the onset of the attack and the administration of rhC1-INH was correlated with the time when the symptoms stopped worsening (R = 0.3212; p = 0.0096) and the time to complete resolution of the symptoms (R = 0.4774; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). The time to response to the drug differed with attack location. The efficacy and safety of rhC1-INH persisted after repeated use. None of the patients experienced a recurrence of the HAE attack or drug-related systemic adverse events. The mean VAS score of patient satisfaction was 93.14. Home treatment with rhC1-INH was an effective and well-tolerated therapy for all types of HAE attacks.