Association of Low Ficolin-Lectin Pathway Parameters with Cardiac Syndrome X.

In patients with typical angina pectoris, inducible myocardial ischaemia and macroscopically normal coronaries (cardiac syndrome X (CSX)), a significantly elevated plasma level of terminal complement complex (TCC), the common end product of complement activation, has been observed without accompanying activation of the classical or the alternative pathways. Therefore, our aim was to clarify the role of the ficolin-lectin pathway in CSX. Eighteen patients with CSX, 37 stable angina patients with significant coronary stenosis (CHD) and 54 healthy volunteers (HC) were enrolled. Serum levels of ficolin-2 and ficolin-3, ficolin-3/MASP-2 complex and ficolin-3-mediated TCC deposition (FCN3-TCC) were determined. Plasma level of TCC was significantly higher in the CSX than in the HC or CHD group (5.45 versus 1.30 versus 2.04 AU/ml, P < 0.001). Serum levels of ficolin-2 and ficolin-3 were significantly lower in the CSX compared to the HC or CHD group (3.60 versus 5.80 or 5.20 µg/ml, P < 0.05; 17.80 versus 24.10 or 26.80 µg/ml, P < 0.05). The ficolin-3/MASP-2 complex was significantly lower in the CSX group compared to the HC group (92.90 versus 144.90 AU/ml, P = 0.006). FCN3-TCC deposition was significantly lower in the CSX group compared to the HC and CHD groups (67.8% versus 143.3% or 159.7%, P < 0.05). In the CSX group, a significant correlation was found between TCC and FCN3-TCC level (r = 0.507, P = 0.032) and between ficolin-3/MASP-2 complex level and FCN3-TCC deposition (r = 0.651, P = 0.003). In conclusion, in patients with typical angina and myocardial ischaemia despite macroscopically normal coronary arteries, low levels of several lectin pathway parameters were observed, indicating complement activation and consumption. Complement activation through the ficolin-lectin pathway might play a role in the complex pathomechanism of CSX.

Complement activation and its prognostic role in post-cardiac arrest patients.

Cardiac arrest causes generalized ischaemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34 °C body temperature for 24 h and then allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and 24 h, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9 and Bb) were measured by ELISA in blood samples. Patients were followed up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 h after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose post-cardiac arrest patients.

Evidence-based hydro- and balneotherapy in Hungary--a systematic review and meta-analysis.

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.

Serum concentration of immunoglobulin G-type antibodies against the whole Epstein-Barr nuclear antigen 1 and its aa35-58 or aa398-404 fragments in the sera of patients with systemic lupus erythematosus and multiple sclerosis.

Several studies suggest that infection by Epstein-Barr virus (EBV) might be one of the environmental factors which facilitates the development of autoimmune disorders in genetically susceptible individuals. Recent data indicate that high anti-Epstein-Barr nuclear antigen 1 (EBNA)-1 immunoglobulin (Ig)G titre is a strong risk factor for multiple sclerosis (MS) in patients both with and without the main genetic predisposing trait, human leucocyte antigen (HLA)-DRB1*15:01. Because no similar studies have been published in systemic lupus erythematosus (SLE) patients, we determined the HLA-DRB1*15:01 carrier state and the serum titres against the whole EBNA-1 and its small fragments aa35-58 and aa398-404 in 301 SLE patients, 135 MS patients and in 345 healthy controls. The carrier state of the HLA-DRB1*15:01 allele was deduced from genotyping of a tagSNP (rs3135388) by applying a Taqman-based assay. The serum concentrations of antibodies to EBNA-1 and its aa35-58 or aa398-404 fragments were determined using a commercial assay (ETI-EBNA-G) and home-made enzyme-linked immunosorbent assays, respectively. The serum concentration of anti-EBNA-1 antibodies was significantly (P < 0·001) higher both in MS and SLE patients than in controls. Similar significant differences were found both in HLA-DRB1*15:01 carriers and non-carriers. Furthermore, titres of antibodies against the aa35-58 EBNA-1 fragment were elevated both in MS and SLE patients. By contrast, the levels of aa398-404 EBNA-1 antibodies were elevated significantly only in the SLE patients. These findings indicate that high anti-EBNA-1 IgG titres are HLA-DRB1*15:01-independent risk factors not only for MS, but also for SLE, while high antibody titres against the aa398-404 fragment are characteristic for SLE.

Circulating ficolin-2 and ficolin-3 in normal pregnancy and pre-eclampsia.

Ficolins are soluble molecules of the innate immune system that recognize carbohydrate molecules on microbial pathogens, apoptotic and necrotic cells. They act through two distinct routes: initiating the lectin pathway of complement activation and mediating a primitive opsonophagocytosis. In this study, we measured plasma levels of ficolin-2 and ficolin-3 in 60 pre-eclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by enzyme-linked immunosorbent assay (ELISA). Circulating levels of complement activation products (C4d, C3a, SC5b9), angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and markers of endothelial activation (von Willebrand factor antigen), endothelial injury (fibronectin) and trophoblast debris (cell-free fetal DNA) were also determined. Plasma levels of ficolin-2 were significantly lower in healthy pregnant than in healthy non-pregnant women, while ficolin-3 levels did not differ significantly between the two groups. Furthermore, pre-eclamptic patients had significantly lower ficolin-2 and ficolin-3 concentrations than healthy non-pregnant and pregnant women. In the pre-eclamptic group, plasma ficolin-2 levels showed a significant positive correlation with serum placental growth factor (PlGF) concentrations and significant inverse correlations with serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1), blood urea nitrogen and creatinine, serum lactate dehydrogenase activities, as well as with plasma VWF:antigen, fibronectin and cell-free fetal DNA concentrations. In conclusion, circulating levels of ficolin-2 are decreased in the third trimester of normal pregnancy. There is a further decrease in plasma ficolin-2 concentrations in pre-eclampsia, which might contribute to the development of the maternal syndrome of the disease through impaired removal of the trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed pre-eclamptic placenta.

Dense deposit disease in an adolescent male mimicking acute post-streptococcal glomerulonephritis.

BACKGROUND: Dense deposit disease (DDD), a subtype of complement factor 3 glomerulopathy (C3G), is a rare entity associated with dysregulation of the alternative complement pathway. It usually affects children, with a 50% likelihood of progression to end-stage renal disease within ten years of diagnosis. Description of the case: We report the case of an adolescent male with acute nephritic syndrome and nephrotic range proteinuria, initially diagnosed as acute post-streptococcal glomerulonephritis (APSGN). Despite his spontaneous improvement, renal biopsy, performed due to a persistently low C3 level for over 18 weeks, confirmed the diagnosis of DDD. Complement and genetic studies showed high levels of C3-nephritic factor and risk polymorphisms for developing the disease. He was treated with prednisolone and mycophenolate mofetil (MMF). At the last follow-up, 15 months from onset, the serum creatinine level and 24h-hour total protein excretion were normal. CONCLUSION: C3G (including the DDD subtype) should be suspected in apparent APSGN with atypical clinical features at presentation/follow-up, even in the case of spontaneous improvement. Timely and accurate diagnosis, based on histopathological, complement, and genetic studies, is important to initiate the appropriate treatment aimed at preventing or slowing the disease progression. HIPPOKRATIA 2020, 24(4): 191-193.

Adrenomedullin and endothelin-1 are related to inflammation in chronic heart failure.

BACKGROUND: Adrenomedullin (ADM) and endothelin-1 (ET-1) are novel promising peptide biomarkers in chronic heart failure (CHF). According to recent studies among their pleiotropic effect they play roles in the regulation of inflammation. The aim of the study was to measure the above mentioned two vasoactive peptides in parallel in a well characterized population of patients with CHF, and study their associations with inflammatory markers. MATERIALS AND METHODS: A total of 186 patients (138 male, 48 female) with <45% left ventricular ejection fraction (LVEF), and without acute inflammatory disease, were enrolled. Plasma midregional-proADM (MR-proADM) and C-terminal-proET-1 (CT-proET-1) were determined by a novel sandwich immunoluminometric assay. RESULTS: Increased MR-proADM and CT-proET-1 plasma levels were measured in patients with severe CHF (NYHA III-IV) as compared to the group of NYHA I-II (p<0.0001). MR-proADM and CT-proET-1 levels showed significant negative correlation with serum albumin and prealbumin levels (p

Association of elevated serum heat-shock protein 70 concentration with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia: a case-control study.

Our aim was to investigate the association between serum heat-shock protein (Hsp) 70 concentration and hypertensive disorders of pregnancy. One hundred and forty-two pregnant women with hypertensive disorders (93 with preeclampsia, 29 with transient hypertension of pregnancy and 20 with superimposed preeclampsia) and 127 normotensive, healthy pregnant women were included in the study. Serum Hsp70 concentration was measured using enzyme-linked immunosorbent assay. The serum Hsp70 concentration was significantly higher in patients with transient hypertension of pregnancy, in preeclamptic patients and in patients with superimposed preeclampsia than in the control group (median (25-75 percentile): 0.66 (0.52-0.84), 0.55 (0.42-0.80), 0.61 (0.42-0.91) ng/ml vs 0.31 (0.27-0.39) ng/ml, respectively; P<0.001). Multivariate logistic regression analysis showed independent association of elevated serum Hsp70 level with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia. The difference in serum Hsp70 concentration between preeclamptic patients and the control group was statistically significant in each gestational age category. In the groups of preeclamptic and superimposed preeclamptic patients, there was no significant difference in serum Hsp70 concentration between mild and severe preeclamptic patients, between patients with late and early onset of the disease, as well as between preeclamptic patients without and with foetal growth restriction. In conclusion, serum Hsp70 concentration is elevated in transient hypertension of pregnancy, in preeclampsia and in superimposed preeclampsia. Circulating Hsp70 may not only be a marker for these conditions, but might also play a role in their pathogenesis. However, further studies are needed to explore its role in the pathogenesis of hypertensive disorders of pregnancy.

Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis.

BACKGROUND: Studies 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 RESULTS: A 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). CONCLUSIONS: High 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.

The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review.

The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past couple of years. These ubiquitous, well-conserved proteins account for 1-2% of all cellular proteins in most cells. However, their precise function is still far from being elucidated. Their involvement in the aetiology of several autoimmune diseases, in various infections, in recognition of malignant cells, and in antigen-presentation already demonstrates the essential role they likely will play in clinical practice of the next decade. The present review summarizes our current knowledge about the cellular functions, expression, and clinical implications of the 90-kDa molecular chaperone family and some approaches for future research.

Defensins purified from human granulocytes bind C1q and activate the classical complement pathway like the transmembrane glycoprotein gp41 of HIV-1.

The transmembrane glycoprotein gp41 of HIV-1 contains a C1q binding domain (HIVenv 583-610) and activates the human complement system through the classical pathway. Based on structural and functional similarities between human defensins (human neutrophil peptide, HNP 1-3) and synthetic peptides representing the env 583-610 region of HIV-1, we found it interesting to investigate the C1q binding and complement activating ability of human defensins. Human defensins were purified and characterized by size exclusion chromatography, ultrafiltration, gel electrophoresis and HPLC. The complement activating ability of the purified peptides was assessed in a solid-phase immunoassay. Defensins, fixed to an ELISA plate, were able to bind the C1q subcomponent of the first complement component (C1), triggering the classical pathway of complement activation which led to C4b binding to the plate. Reduction and subsequent alkylation of disulfide bridges of defensins greatly decreased the C1q binding ability but complement activation (C4b binding) remained high. Further acetylation of the reduced defensin peptide resulted in a molecule which bound very little or no C1q but still activated the complement cascade. These phenomena indicate that defensins interact with the complement system via C1q-dependent and C1q-independent mechanisms, and extend the number of functional similarities between defensins and gp41 of HIV-1 to include C1q binding and complement activation.

A 60 kD heat-shock protein-like molecule interacts with the HIV transmembrane glycoprotein gp41.

The heat-shock protein hsp60 is typically found in mitochondria, but, in smaller amounts, also in the cell cytoplasm and associated with the cell membrane. Since heat-shock proteins are known to interact with a variety of molecules and since purified HIV-1 particles were described to contain hsp60 molecules, we tested the possibility that a previously described putative receptor for HIV transmembrane protein gp41 is identical to hsp60. The gp41-binding human protein P62 was purified from H9 and Raji cell lysates by a gp41-coupled affinity column. We could show crossreactivity of both polyclonal and monoclonal anti-hsp60 antibodies with the purified P62. In addition we analyzed binding of P18, a soluble gp41 fragment harboring the extracellular domain (Env aa539-684), to recombinant hsp60. Hsp60 bound well to P18-coated ELISA plates whereas HIV-1 surface protein gp120 induced no binding of hsp60. Preincubation of hsp60 with gp41 abolished the binding. The possible role of this molecule as a cofactor in the pathogenesis of HIV disease is discussed.

Strong correlation between the complement-mediated antibody-dependent enhancement of HIV-1 infection and plasma viral load.

OBJECTIVE: We have previously demonstrated that complement-mediated antibody-dependent enhancement (C-ADE) of HIV-1 infection correlates with accelerated immunosuppression and disease progression in HIV-1-infected individuals. In the present work the relationship between C-ADE and plasma HIV-1 RNA concentrations was studied to determine the effect of C-ADE on viral replication. METHODS: Three studies were performed: (a) C-ADE and HIV-1 RNA concentrations were determined in the serum and plasma aliquots taken at the same time from 98 HIV patients, mostly in the advanced stage of the disease; (b) the above two parameters as well as HIV enzyme-linked immunosorbent assay (ELISA)-reactive antibodies (Abbott HIV 1/2 test), and p24 antigen levels (Abbott antigen test; Abbott, Delkenheim, Germany) were determined in four seroconversion panels purchased from the Boston Biomedica firm; (c) changes of HIV-1 RNA concentration and C-ADE during a 17 month follow-up period were determined in 18 HIV-infected patients. C-ADE was measured by the method previously established in our laboratories. The results were expressed by an enhancement/neutralization index (E/NI). HIV-1 RNA levels were determined with the Amplicor monitor kit (Roche, Basel, Switzerland), and in some experiments with the nucleic acid sequence based amplification (Organon Teknika, Turnhout, Belgium) kits. RESULTS: (a) We found a highly significant (P<0.0001) positive correlation between E/NI values reflecting the extent of HIV-1 infection enhancement and plasma HIV-1 RNA levels. Both E/NI and HIV-1 RNA levels negatively correlated to the CD4 cell counts. (b) C-ADE was first detected just before, or concomitantly with, seroconversion in 4/4 seroconversion panels. (c) Both E/NI values and HIV-1 RNA levels significantly (P<0.001) increased during a 17 month observation period in 18 HIV-infected patients. CONCLUSION: We found strong association between the extent of the complement-mediated antibody-dependent enhancement of HIV-1 infection and the plasma viral load in HIV patients. On the basis of these findings, C-ADE correlates with HIV replication in vivo, and potentially contributes to the progression of HIV disease.

Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection.

OBJECTIVE: To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-ADE) of HIV infection which may play a significant role in the progression of HIV-disease. METHODS: In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1IIIB and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources. RESULTS: All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum. CONCLUSION: These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.

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.

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.

Anti-cholesterol antibodies (ACHA) in patients with different atherosclerotic vascular diseases and healthy individuals. Characterization of human ACHA.

In animal experiments the protective role of anti-cholesterol antibodies (ACHA) in the development of atherosclerosis has been demonstrated. Despite the fact that ACHA are present in the serum of healthy humans, no data on the occurrence of these antibodies in human diseases are available. We determined serum concentrations of IgG type ACHA by an enzyme immunosorbent assay in 600 patients with atherosclerotic vascular diseases (86 patients with peripheral occlusive atherosclerosis, 146 patients with cerebrovascular diseases, 341 patients with severe coronary heart disease (CHD) who received aorto-coronary by-pass, 27 patients with myocardial infarction who did not undergo by-pass operation), in 57 patient controls (complaints of CHD, without coronarographic alterations) and in 218 healthy individuals. ACHA were present in the sera of all persons tested. No serum cofactor is needed for the binding of human ACHA to solid phase cholesterol, binding can be inhibited dose-dependently by LDL and even more strongly with LDL/VLDL preparations purified from human serum. ACHA levels were found to be considerably lower in patients with peripheral occlusive atherosclerosis and cerebrovascular diseases compared with the levels in healthy individuals. By contrast, the ACHA levels of patients with CHD were considerably higher. No differences in the IgG subclass distribution and binding efficiency of ACHA in the sera of CHD patients and controls were found. Thus, our present findings indicate that both low and high ACHA production may be associated with different atherosclerotic vascular diseases.

Mannan-binding lectin serum concentrations in HIV-infected patients are influenced by the stage of disease.

Serum concentrations of mannan-binding lectin (MBL) were determined in the sera of 67 HIV-seropositive patients in different stages of HIV disease and in the sera of 75 HIV-seronegative healthy individuals. In the asymptomatic (AS) HIV-infected persons MBL concentrations were found to be significantly (P < 0.05) lower than in the HIV-seronegative controls, whereas in the AIDS patients they were not. Very low (< or = 25 ng/ml) MBL serum concentrations were detected in 5/19 (26.3%) and 7/75 (9.3%) of the AS HIV-seropositive and HIV-seronegative individuals, respectively (P = 0.06). In the sera of the HIV-infected patients, MBL levels positively correlated to the neopterin concentrations (Spearman correlation coefficient, 0.401, P = 0.0009) while they negatively correlated to the percentage (-0.447, P = 0.0011) and absolute number (-0.453, P = 0.0012) of the CD4+ lymphocytes. These observations indicate that MBL level, which is under strict genetic control, may influence the susceptibility to HIV infection and the progression of HIV disease.

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.