G. Füst

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.

The efficacy of short-term danazol prophylaxis in hereditary angioedema patients undergoing maxillofacial and dental procedures

PURPOSE This study evaluated the efficacy of short-term danazol prophylaxis in hereditary angioedema patients undergoing maxillofacial or dental procedures. PATIENTS AND METHODS Twelve patients with a history of edema after dental procedures were administered danazol (600 mg/d) 4 days preoperatively and 4 days postoperatively. The serum levels of complement components were determined preoperatively and postoperatively as well as at 6, 12 and 24 hours in six patients. RESULTS None of the 12 patients developed angioneurotic edema. The serum levels of the complement components were decreased immediately after surgery and returned to normal within 24 hours. CONCLUSION The short-term prophylactic use of danazol in patients with hereditary angioedema undergoing oral surgery is an effective preventive measure.

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.

Association of polymorphisms and allelic combinations in the tumour necrosis factor-α-complement MHC region with coronary artery disease

It is a complicating factor in the search for disease associated genes in the human population that most diseases are very heterogeneous clinically and that certain genetic factors may not alone cause susceptibility to a disease, but in association with other genetic and environmental factors. It is especially true for coronary artery disease (CAD) and disease susceptibility genes in the human major histocompatibility complex (MHC). Given the conservation of whole haplotypes (polymorphic frozen blocks or extended haplotypes) and the cis acting genes within the MHC, it is highly likely that disease association is the result of a multiplicity of interactive genetic influences rather than a single gene.1 By tradition, a disease is said to be MHC associated if the frequency of one or more alleles is increased or decreased significantly when a patient group is compared with a relevant control group. This approach cannot uncover the possible interactions of different alleles and may result in both false positive and false negative association. In our study on patients with CAD, we make an attempt to investigate not only the impact of single allelic variations within the MHC, but also the impact of a combination of these allelic variations on susceptibility to the disease. The tumour necrosis factor-α ( TNFα ) gene is located on chromosome 6 between the class I and III clusters of the human MHC.2 It has been suggested that TNFα plays a role in cardiovascular pathophysiology as it may affect lipid metabolism3 and predispose to obesity related insulin resistance.4 Several TNFα variants with polymorphisms in their promoter regions have been described.5 Two of them (−308G-A and −238G-A) have been found to be associated with a variety of MHC linked diseases.5–7 Complement factor genes are located just a few hundred kilobases (kb) from the …

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.

Low activity of the classical complement pathway predicts short survival of patients with chronic lymphocytic leukaemia

The activities of the classical (CP) and alternative (AP) complement pathways as well as the levels of some complement components and circulating immune complexes were measured in 43 patients with chronic lymphocytic leukaemia (CLL) between 1980 and 1984. Depressed C P activities were frequently found in these patients. Clinical course of the disease in the patients was followed until 1992, and compared with the initial complement values. During the follow‐up period 36 patients died, death of 33 patients being related to the underlying disease. A strong positive correlation (P < 0.01) was found between the length of survival of the patients and the initial CP values. Patients were divided into two groups: group A, short‐term survivors, i.e patients who died in CLL‐related complications within 3 years after the complement measurements; and group B, long‐term survivors who died ≥ 4 years after the complement measurements due to any cause, or were alive at the end of the follow‐up period. Average CP values in Group B were almost twice those in group A (P= 0.002), and a similar but less pronounced difference was found in C3 levels (P= 0.055). These differences were even more marked (P= 0 0006 and P= 0.0015, respectively) when only patients in Rai stage 2 and 3 were considered. Low classical pathway activities predicted short survival time: according to the logrank test, patients in Rai stage 2–3 with low (< mean − 2 s.d. of the normal values), and normal CP levels survived for 2.0 ± 1.1, and 4.6 ± 3.0 years, respectively. All the nine and 11/13 patients with low CP and C4 levels, respectively, died within 3 years after the complement measurements were made. These findings indicate that complement measurements performed in CLL patients have a clinical value.

High anti-EBNA-1 IgG levels are associated with early-onset myasthenia gravis

Background:  Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acethylcholine receptor (AchR) of the neuromuscular junction in the majority of patients.

Usefulness of detection of complement activation products in evaluating SLE activity

Complement activation products, such as C1rs-C1inh, specific for the activation of the classical pathway, C3b(Bb)P, specific for the activation of the alternative pathway and SC5b-9, specific for common terminal pathway of the complement cascade, were measured in healthy donors and in patients with clinically active and inactive systemic lupus erythematosus (SLE). Plasma levels of C3b(Bb)P and SC5b-9 were moderately, those of C1rs-C1inhibitor (C1rs-C1inh) were markedly elevated in patients with clinically inactive SLE, compared with healthy controls. The difference between active and inactive stages of the disease was best reflected by C3b(Bb)P plasma concentration (P < 0.001), which also showed the highest correlation with the SLEDAI (Rs = 0.41 P < 0.001) and which was the most useful in distinguishing active and inactive sample pairs as well. The difference between SC5b-9 levels in the active and inactive stages was also significant (P = 0.007), while that of C1rs-C1inh did not differ significantly (P = 0.136). The correlation of the SLEDAI with SC5b-9 was 0.3 (P = 0.015), while with C1rs-C1inh it was 0.21 (P = 0.089). These findings suggest that the measurement of complement activation products, especially that of the alternative pathway, are sensitive markers of the activity of SLE and can be used for clinical purposes.

C1-inhibitor autoantibodies in SLE

The presence of anti-C1-inhibitor (anti-C1-INH) autoantibodies is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence, diagnostic value, and/or significance in systemic lupus erythematosus (SLE). In a multicentre study, we determined the levels of autoantibodies to C1-inhibitor in sera from 202 patients with SLE and 134 healthy controls. Additional clinical and laboratory parameters, such as organ involvement, as well as anti-C1q, anti-double-stranded DNA antibody, erythrocyte sedimentation rate, C-reactive protein, C3 and C4 serum complement levels have been studied in patients. The level of anti-C1-INH IgG was significantly higher (p = 0.034) in SLE patients, than in the controls. A high anti-C1-INH level of ≥0.4 U/ml (mean of controls + 2 SD) was found in 17% of the patients, but in only 4% of the controls (p = 0.0003). The SLEDAI score was significantly higher (p = 0.048) and the duration of SLE was significantly longer (p = 0.0004) among patients with elevated anti-C1-INH levels compared with patients without this autoantibody (median disease duration 8 vs. 17 years, respectively). Anti-C1-INH level was not correlated with any other laboratory parameter or organ manifestation of the disease. These findings indicate that the anti-C1-INH level is higher in SLE patients than in healthy controls and furthermore, the anti-C1-INH level correlates with the duration and activity of the disease. Lupus (2010) 19, 634—638.

Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients.

ObjectiveWe investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn’s disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis.SubjectsWe analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants.MethodsThe analysis was carried out using PCR–RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls.ResultsWe observed no significant difference of the examined variants between the patient and control groups.ConclusionsOur results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.