Laura Horváth

Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients

The central role of chemokines in the pathogenesis of atherosclerosis has been made clear. Recently polymorphisms in the gene regulatory region of MCP-1 and in the promoter region of RANTES have been found, which increase the expression of these chemokines. We investigated the role of these polymorphisms together with the chemokine SDF-1-801A and the chemokine receptors CCR2-64I and CCR5Delta32 mutations in 318 patients with coronary artery disease (CAD) referred to coronary bypass surgery, comparing them with 320 healthy controls. The prevalence of the MCP-1 -2518 G/G homozygotes was significantly higher among CAD patients than among controls (P<0.005; OR=2.2 (95% CI 1.25-3.92). The Lp(a) levels of CAD patients with G/G genotype were significantly higher than those in patients with G/A or A/A genotypes. No CAD patients homozygous for the CCR5Delta32 and CCR2-64I mutations have been found. The genotype distributions of the two alleles deviated from the Hardy Weinberg equilibrium in patients, indicating that the numbers of homozygotes were significantly lower than expected. The MCP-1 -2518G variant in homozygous form appears as a genetic risk factor for severe CAD. This genotype is associated with elevated Lp(a) levels in patients. Individuals homozygous for CCR2-64I or CCR5Delta32 mutations are at reduced risk for severe CAD.

Independent and Joint Effects of Antibodies to Human Heat-Shock Protein 60 and Chlamydia pneumoniae Infection in the Development of Coronary Atherosclerosis

BackgroundStudies have suggested that the prevalence of antibodies against heat-shock proteins (HSPs), Chlamydia pneumoniae (Cpn), and cytomegalovirus (CMV) is associated with coronary artery disease (CAD), but the independent or joint effects of human (h) HSP60 antibodies and these pathogens in patients have not been fully elucidated. Methods and ResultsA total of 405 subjects (276 patients with CAD and 129 control individuals) were tested for serum antibodies to hHSP60, Cpn, and CMV immediate-early-1 (IE1) antigens. Patients were also assessed for serum cholesterol, triglyceride levels, and smoking habit. Significantly elevated levels of antibodies to hHSP60 and Cpn but not to CMV-IE1 antigens were documented in CAD patients. Multiple logistic regression analysis and subanalyses of selected subjects showed that these associations were independent of age, sex, smoking, and serum lipid levels. Antibodies to hHSP60 and Cpn did not correlate quantitatively; however, the relative risk of disease development was substantially increased in subjects with high antibody levels to both hHSP60 and Cpn, reaching an odds ratio of 82.0 (95% CI 10.6 to 625.0). ConclusionsHigh levels of antibodies to hHSP60 and Cpn are independent risk factors for coronary atherosclerosis, but their simultaneous presence substantially increases the risk for disease development.

Comparative study on antibodies to human and bacterial 60 kDa heat shock proteins in a large cohort of patients with coronary heart disease and healthy subjects

Background Recent observations indicate an association between antibodies against mycobacterial heat shock protein (hsp65) and coronary heart disease (CHD). Previously, we reported on marked differences in antigen specificity and complement activating ability of anti‐hsp65 antibodies and auto‐antibodies against human heat shock protein, hsp60. Here, we investigated whether there are differences between antih‐sp65 and anti‐hsp60 antibodies in their association with CHD.

Antibodies against different epitopes of heat-shock protein 60 in children with type 1 diabetes mellitus

The aim of this study was to investigate the amounts and epitope specificity of antibodies against heat shock protein 60 (hsp60) in the sera of type 1 diabetic and healthy children. Antibodies specific for peptide p277 of human hsp60 and of M. bovis as well as for human hsp60, M. bovis hsp65 proteins were measured by ELISA. Other autoantibodies (islet cell antibodies, glutamate decarboxylase antibodies and IA-2 antibodies) were also determined. A total number of 83 serum samples from children with type 1 diabetes mellitus and 81 samples of control children were investigated. Epitope scanning of the hsp60 for linear antibody epitopes was carried out using synthetic peptides attached to pins. The antibody levels specific for peptide p277 of human- and of M. bovis origin were significantly (human: P=0.0002, M. bovis: P=0.0044) higher in the diabetic children group than in the healthy children. We could not find significant difference in the antibody levels to whole, recombinant hsp proteins among the examined groups of children. Antibodies to two epitope regions on hsp60 (AA394-413 and AA435-454) were detected in high titres in sera of children with diabetes mellitus. The first region similar to the sequence found in glutamate decarboxylase, whereas the second one overlaps with p277 epitope to a large extent. Presence of antibodies to certain epitopes of hsp60 (AA394-413-glutamic acid decarboxylase-like epitope; AA435-454-p277-like epitope) in diabetic children may reflect their possible role in the autoimmune diabetogenic process of the early diabetes.

Levels of antibodies against C1q and 60 kDa family of heat shock proteins in the sera of patients with various autoimmune diseases

Previously a strong positive correlation was found between antibodies to C1q (C1qAb) and antibodies against human heat shock protein (hsp60) and mycobacterial hsp65 in HIV infected patients. Here the levels of these antibodies were measured in the sera of patients with different autoimmune diseases (122 systemic lupus erythematosus (SLE), 55 systemic sclerosis, 33 undifferentiated connective tissue disease (UCTD), 27 primary Raynaud syndrome, 21 rheumatoid arthritis (RA), 14 polymyositis/dermatomyositis (PM/DM), and 192 healthy blood donors. The prevalence of IgG C1qAb was found to be high (P<0.0001 as compared to the healthy controls) only in the SLE group. The levels of the anti-hsp60 (P=0.0094) and anti-hsp65 (P=0.0108) antibodies were high only in the UCTD patients. No correlation was found between the C1qAb and anti-hsp antibodies in any group except a significant (P=0.011) positive correlation between C1qAb and hsp65 antibodies in the patients with UCTD. These findings indicate that the autoantibodies against C1q are heterogeneous: in different diseases different types of C1qAb may dominate.

Frequencies of certain complement protein alleles and serum levels of anti-heat-shock protein antibodies in cerebrovascular diseases

Background and Purpose A strong correlation exists between the intensity of atherosclerotic alterations in different arteries. Marked differences exist, however, in the age and sex distribution and risk factors for coronary heart disease (CHD) and cerebrovascular disease (CVD). We therefore performed genetic and immunologic studies in patients with CVD. Methods We studied 292 patients with CVD (stroke or transient ischemic attack) and as control either 198 healthy blood donors and 485 healthy elderly (aged >60 years) people (genetic study) or 94 blood donors aged 45 to 60 years and 49 healthy elderly (aged >60 years) people (anti–heat-shock protein [hsp] measurements). Allele frequencies of 3 genes (C4A, C4B, and C3) encoding proteins of the complement system were determined by electrophoresis and immunofixation. Serum concentration of autoantibodies against 60-kDa heat-shock protein (anti-hsp60) was measured by the enzyme-linked immunosorbent assay method. Results Marked differences were observed between CVD patients and controls in the genetic studies. In the CVD patients aged >60 years, the frequency (11.3%) of the deficient allele of the C4B gene (C4B*Q0) was significantly (P =0.0003) higher than that of the healthy controls (5.4%). By contrast, in the group aged 45 to 60 years, the frequency of the C4B*Q0 allele was lower in patients than in controls. Serum concentration of anti-hsp60 in the CVD patients did not differ from control values. Conclusions In previous studies C4B*Q0 frequency was reported to be higher in CHD patients aged 45 to 60 years than in aged-matched controls. Moreover, high anti-hsp60 levels were found in CHD patients. These findings contrast with our present report of lower frequency of C4B*Q0 in CVD patients. Therefore, genetic and immunologic factors may at least partly explain the differences between the natural history and risk factors of CHD and CVD.

Multiple Myeloma of the Central Nervous System: 13 Cases and Review of the Literature

Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment. Recent case reports show promising effectivity of pomalidomide and marizomib.

Thalidomidkezelés relabált, diffúz nagy B-sejtes lymphomában idős betegekben. Három eset bemutatása

Absztrakt: A diffuz nagy B-sejtes lymphoma (DLBCL) a leggyakoribb malignus lymphomatipus, amely a non-Hodgkin-lymphomak (NHL) 31%-at teszi ki. A standard kemoterapias protokollok jelentős toxicitasuk miatt nem vagy nehezen alkalmazhatoak az idősebb betegpopulacioban, kulonosen a relabalt esetekben, ahol kurativ lehetőseget leginkabb a nagy dozisu kezeles es a ver-őssejtatultetes jelenthetne. Egyre tobb adat lat napvilagot a thalidomid es az ujabb IMiD-ek (lenalidomid, pomalidomid) kedvező hatasairol az NHL kezeleseben, amelyek reszei a standard kezelesnek myeloma multiplexben es myelodysplasias szindromaban. Az IMiD-ek kiterjedt anti-angiogenetikus, immunmodulans es gyulladasellenes hatasuknak koszonhetik az egyre szeleskorűbb alkalmazast. 2010-ben azonositottak az E3-ubiquitin-ligaz-komplex egyik komponenset, a cereblont, amely a thalidomid molekularis tamadasi pontja. Az irodalomban kozolt eredmenyek alapjan thalidomidkezelest inditottunk harom relabalt, idős DLBCL-es betegunknel. Ket esetben kozponti i...

A krónikus myeloid leukaemia korszerű diagnosztikája és kezelése

Absztrakt A kronikus myeloid leukaemia klonalis myeloproliferativ betegseg, amelyben a haemopoeticus őssejt malignus transzformacioja kovetkezik be a 9-es es a 22-es kromoszoma hosszu karjai kozotti reciprok transzlokaciobol szarmazo BCR-ABL1 fuzios gen altal eredmenyezett konstitutivan aktivalt tirozinkinaz aktivitasanak koszonhetően. A korabbi kezelesi lehetősegek ellenere a progressziv betegseg kezeleseben uj tavlatokat nyitott a BCR-ABL1 fuzios feherjet gatlo tirozinkinaz-gatlo keszitmenyek felfedezese. A terapias siker megiteleset ennek megfelelően a kezeles mellett elert molekularis valasz melysege hatarozza meg. Jelenleg hazankban mar harom tirozinkinaz-gatlo keszitmeny elerhető a kronikus myeloid leukaemia kezelesere. Szakmai iranyelvunk osszefoglalja a kronikus myeloid leukaemia korszerű kezelesenek Magyarorszagon aktualis szempontjait, valamint az azok mellett szukseges terapias valasz melyseget. Orv. Hetil., 2016, 157(37), 1459–1468.