Clinical significance of antibodies against oxidised low density lipoprotein in early RA.
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Adult↗
Biomedical subjects
T Palosuo
Publications and source records attributed to T Palosuo.
Significance of rubber elongation factor as a latex allergen.
IgE-mediated hypersensitivity to proteins eluting from surgical gloves and other natural rubber products is a well-recognized allergic condition with special impact to health care workers and sensitized patients. Since rubber elongation factor (REF) has been suggested to be the major latex allergen (Hev b 1) we purified REF from rubber particles using electrophoresis and electroelution and reevaluated the occurrence of IgE antibodies to purified REF. The purified protein was subjected to tryptic digestion, peptide separation and amino acid sequencing. Amino acid sequences of 9 tryptic peptides from the purified 14-kD protein gave 100% homology to REF. In immunoblotting, sera from 4 of 6 latex-allergic children with spina bifida or other congenital anomalies exhibited IgE antibodies against REF whereas only 1 serum from the 30 other latex-allergic patients had similar antibodies. In IgE ELISA 8/45 (18%) latex-allergic patients had IgE antibodies to purified REF, whereas 30 (67%) of the same patients had IgE antibodies to purified prohevein, another rubber protein, recently shown to be a major natural rubber latex allergen. The observed overall low frequency of IgE antibodies to purified REF, as measured by two specific IgE assays, indicates that REF is one but not the most significant allergen among the natural rubber latex proteins.
Adolescent↗
Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men.
Antiphospholipid antibodies in patients with "antiphospholipid syndrome" may be directed at least in part against plasma phospholipid-binding proteins, such as beta 2-glycoprotein I or prothrombin, which are involved in the control of thrombosis and haemostasis. IgG-class antibodies against prothrombin and beta 2-glycoprotein I were measured by enzyme-linked immunoassay in initially healthy middle-aged dyslipidaemic men (non-high-density lipoprotein > 5.2 mml/l). Serum samples had been drawn at entry to a 5-year coronary primary-prevention trial with gemfibrozil from 106 subjects who experienced either a non-fatal myocardial infarction or cardiac death during the follow-up and from 106 subjects without coronary episodes, matched for treatment group (gemfibrozil/placebo) and geographical area. The antiprothrombin antibody level, as expressed in optical density units, was significantly higher in patients than in controls (0.26 +/- 0.17 versus 0.22 +/- 0.09; p < 0.02). A high level of antiprothrombin antibodies (highest tertile of distribution) predicted a 2.5-fold increase in the risk (95% confidence interval 1.2-5.3) of myocardial infarction or cardiac death. The distribution of IgG-class antibodies against beta 2-glycoprotein I did not differ significantly between cases and controls. The joint effect of antiprothrombin antibodies and other factors associated with hypercoagulative state: triglyceride level, lipoprotein(a) and smoking, was multiplicative for the risk. Antiprothrombin antibodies are a new immunological predictor of myocardial infarction and the effect of these antibodies may be mediated by hypercoagulative mechanisms.
Apolipoproteins↗
Crossreactivity between allergens in natural rubber latex and banana studied by immunoblot inhibition.
BACKGROUND: An association between allergic reactions to natural rubber latex and to banana has been reported but the immunochemical properties of the putative cross-reacting allergens remain unknown. OBJECTIVE: To study extracts of banana and natural rubber latex and sera from latex-allergic patients for possible crossreacting allergens and IgE antibodies. METHODS: Sera from 22 latex-allergic patients and 22 control subjects with no evidence of allergy to latex or to banana were studied. All patients had positive and controls negative reactions in skin-prick testing using an eluate of latex gloves. IgE antibodies to natural rubber latex and to banana were evaluated by immunoblotting and by radioallergosorbent test (RAST) and crossreactivity between allergens in banana and natural rubber latex by immunoblot inhibition. Skin-prick testing was used to examine in vivo reactivity to banana. RESULTS: Ten of the 22 (45%) latex-allergic patients sera recognized altogether 14 allergens in banana by immunoblotting. The most frequently identified banana allergens were 23, 32, 36, 39 and 47 kDa proteins. The banana skin-prick test was positive in 14 of 18 (78%) latex-allergic patients studied and banana RAST in 12 of 14 patient sera tested. Fourteen of 21 interviewed patients reported symptoms from eating or handling bananas. In immunoblot inhibition studies a dose-dependent inhibition of IgE binding to banana extract with natural rubber latex proteins was observed in all five patient sera tested and, likewise, the binding of IgE to natural rubber latex extract was inhibited with banana proteins in four of the five patient sera. CONCLUSIONS: The present results confirm the existence of crossreacting allergens in natural rubber latex and banana and provide new information on the immunochemical nature and heterogeneity of these allergens.
Adult↗
Effect of cetirizine on the inflammatory cells in mosquito bites.
BACKGROUND: Mosquito bites frequently cause wealing and delayed papules which appear within a few hours after the bites and may persist for several days. Cetirizine is an effective drug against mosquito bites by decreasing wealing and also the size and pruritus of the delayed bite papules. OBJECTIVES: To characterize inflammatory cells in the delayed mosquito-bite lesions, and to study the effect of cetirizine on the inflammatory cell response. METHODS: Twenty-six mosquito-bite sensitive subjects received cetirizine 20 mg (14 subjects) or placebo (12 subjects) in a double-blind fashion. Aedes aegypti-bites were given on a forearm and serial punch biopsies were taken at 2-, 6- and 24h after the bite exposure. Eosinophils, neutrophils, mast cells, mononuclear cells and T- helper (CD4+) and suppressor (CD8+) lymphocytes were counted from dermal infiltrates. RESULTS: Eosinophils and neutrophils were found already in 2-h bite lesions. Moreover, the number of mononuclear and CD4+ cells increased significantly (P < 0.01) from 2- to 24-h bite lesions. Unexpectedly, the overall numbers of eosinophils (P < 0.05), mononuclear cells (P < 0.01) and CD4+ cells (P < 0.01) were significantly higher in the cetirizine-treated subjects compared with the placebo-treated subjects. CONCLUSIONS: The results suggest that the inflammatory cell response in the delayed mosquito-bite lesions is similar to that occurring in allergic late-phase responses, i.e. an early influx of eosinophils, neutrophils and subsequent accumalation of CD4+ lymphocytes. The reason for the high numbers of eosinophils and CD4+ cells in the cetirizine-treated subjects is not known.
Adult↗
Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men.
BACKGROUND: Data concerning the relation between antiphospholipid (aPL) antibodies and myocardial infarction in subjects without evidence of overt autoimmune disease are conflicting. All published studies have been performed on survivors of myocardial infarction or in patients with established coronary heart disease. The purpose of the present study was to determine whether the presence of aPL antibodies, namely, anti-cardiolipin (aCL) antibodies, carries a risk for myocardial infarction in a prospective cohort. METHODS AND RESULTS: The sera to be studied were drawn at entry from middle-aged dyslipidemic men (non-high-density lipoprotein cholesterol, > or = 5.2 mmol/L) participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil. Samples were tested for IgG-class antibodies to cardiolipin by an ELISA. The risk was estimated with logistic regression analysis using a nested case-control design with 133 patients (myocardial infarction or cardiac death) and 133 control subjects, matched for treatment (gemfibrozil/placebo) and geographical area. The aCL antibody level, as expressed in optical density units, was significantly higher in patients than in control subjects (0.417 versus 0.361; P < .005). Subjects with the antibody level in the highest quartile of distribution had a relative risk for myocardial infarction of 2.0 (95% confidence interval, 1.1 to 3.5) compared with the remainder of the population. This risk was independent of confounding factors, such as age, smoking, systolic blood pressure, low-density lipoprotein (LDL), and high-density lipoprotein. There was a correlation between the levels of aCL antibodies and antibodies to oxidized LDL (r = .40, P < .001), and their joint effect was additive for the risk. CONCLUSIONS: In a prospective cohort of healthy middle-aged men, the presence of a high aCL antibody level is an independent risk factor for myocardial infarction or cardiac death. Antibodies to cardiolipin and oxidized LDL may, at least in part, represent cross-reactive antibody populations.
Antibodies, Anticardiolipin↗
IgM class autoantibodies in human cord serum.
It has previously been shown that human neonatal B lymphocytes in vitro can synthesize autoantibodies which typically are of IgM class, polyreactive and of low affinity and thought to represent natural autoantibodies. We screened 1034 cord serum specimens to find sera with elevated IgM levels; 98 such sera were further examined by an enzyme-linked immunosorbent assay (ELISA) to determine whether antibodies against a panel of autoantigens could be found. We detected low levels of IgM class antibodies against cardiolipin, pyruvate dehydrogenase, single-stranded DNA, thyroglobulin and Fc fragments of IgG as rheumatoid factors. The IgM concentration correlated with autoantibody levels. The specificity of the autoantibody assays was confirmed by inhibition tests. We conclude that several types of autoantibodies can be found in some sera of newborns and that increased IgM concentration of some neonates may reflect a polyclonal antibody response.
Antibodies, Anticardiolipin↗
Antibodies to oxidized low-density lipoprotein and to cardiolipin in nonpregnant and pregnant women with habitual abortion.
OBJECTIVE: To determine the occurrence of antibodies to oxidized low-density lipoprotein (LDL) in women with a history of habitual abortion before and during pregnancy. DESIGN: Immunoglobulin G class antibodies to malondialdehyde modified LDL were determined by a solid-phase ELISA in 42 habitual aborters before pregnancy, in 39 patients during pregnancy, and in 23 comparable nonpregnant and 22 pregnant control women without a history of abortion. In addition, we assessed the presence of anticardiolipin antibodies by ELISA in the same sera. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Early pregnancy was accompanied by a decrease in the median levels of antibodies to oxidized LDL both in habitual aborters and in the control series. Only one patient exhibited a raised level of antibodies to oxidized LDL before pregnancy but, during pregnancy, nine patients (23%) had elevated levels of antibodies to oxidized LDL, similar to women with a favorable outcome of pregnancy (6/27, 22%) and in women whose current pregnancy also ended in abortion (3/12, 25%). Cardiolipin binding antibodies were detected in three habitual aborters before pregnancy (7%) and in nine women during pregnancy (23%), with a tendency to be more frequent in patients with miscarrying pregnancies than in those with continuing pregnancies (4/12, 33% and 5/27, 19%). Antibodies to oxidized LDL and cardiolipin were simultaneously present in three habitual aborters with continuing pregnancies. CONCLUSIONS: Increased levels of antibodies to oxidized LDL and cardiolipin may be associated with habitual abortion.
Abortion, Habitual↗
Cross-reacting allergens in natural rubber latex and avocado.
BACKGROUND: An association between allergy to latex and avocado has been reported but the responsible cross-reacting allergens have not been identified or characterized. METHODS: Immunoblotting, immunoblot inhibition, and RAST inhibition methods were used to study cross-reactive proteins between natural rubber latex (NRL) and avocado. Sera from 18 patients with previously verified latex allergy were used as the source of IgE antibodies, and 11 of the patients underwent skin prick testing with fresh avocado. RESULTS: Fourteen of the 18 sera (78%) had IgE antibodies that bound to a total of 17 avocado proteins with apparent molecular weights ranging from 16 to 91 kd. Ten most strongly reacting sera were used for immunoblot inhibition studies. When NRL proteins were used as soluble inhibitors, binding of IgE antibodies to solid-phase avocado proteins was inhibited in a dose-dependent manner: 100 micrograms of NRL proteins inhibited IgE binding to 15 of the 17 avocado proteins, and 10 micrograms caused inhibition to 13 protein bands. Comparably, soluble avocado proteins were able to inhibit IgE binding to solid-phase NRL. Corresponding RAST inhibitions were performed with two patient sera; in both, avocado inhibited IgE binding to NRL and in one NRL proteins inhibited IgE binding to avocado. Skin prick test responses to fresh avocado were positive in seven of the 11 patients with latex allergy who were tested. CONCLUSIONS: The large number of inhibitable proteins in immunoblot experiments and clinical observations from skin prick tests suggest considerable immunologic cross-reactivity between NRL and avocado. The observed cross-reacting protein components may be responsible for the recently reported type I hypersensitivity reactions to NRL and avocado in patients with a preexisting allergy to either allergen.
Adolescent↗
Prognostic value of quantitative measurement of rheumatoid factor in early rheumatoid arthritis.
The prognostic value of quantitative measurement of rheumatoid factor (RF) by immunoturbidimetry was evaluated in 78 patients with early rheumatoid arthritis (RA) during a 3-yr follow-up. After starting disease-modifying antirheumatic treatment, a significant improvement in conventional clinical and laboratory variables measuring disease activity was observed, while a steady increase was found in radiological progression. Initial RF levels correlated with radiologically determined joint damage up to 3 yr, whereas no correlation of other initially determined conventional variables of disease activity was found. High levels of RF at entry and persistent RF positivity during the follow-up were markers for destructive disease. Initial RF positivity alone was a sensitive predictor for later joint destruction, but quantitative measurement of the initial RF level and especially repeated measurements of RF seemed to add significantly to the prognostic value of RF in distinguishing between progressive and non-progressive disease in early RA.
Adult↗
Prohevein from the rubber tree (Hevea brasiliensis) is a major latex allergen.
BACKGROUND: There is general agreement that proteins eluting from different natural rubber latex products can cause immediate type hypersensitivity reactions in latex-allergic patients. However, there is as yet no consensus as to what are the most important allergens in natural rubber latex. OBJECTIVE: We wanted to purify and characterize at the primary structure level three natural latex proteins, suggested to represent significant allergens. METHODS: Proteins were purified from ultracentrifuged bottom fraction of natural rubber latex using high performance liquid chromatography gel filtration and reversed phase chromatography. Purified proteins were subjected to tryptic cleavage, peptide separation and amino acid sequencing. Immunoblotting was used to demonstrate IgE antibodies to the purified proteins in sera from latex-allergic patients. RESULTS: A 20 kDa protein was identified by amino acid sequencing as prohevein, a major protein in the rubber tree Hevea brasiliensis, and a 30 kDa natural rubber latex protein as hevamine, another essential rubber tree protein. A third, previously undescribed natural rubber latex protein, showed high homology to several plant endo-1,3-beta-glucosidases. In immunoblotting, the purified prohevein bound IgE antibodies from 24/29 (83%) sera of latex-allergic patients including positive results in 4/6 latex-allergic children with spina bifida or other congenital anomalies. The purified prohevein elicited positive skin-prick test reactions in all six latex-allergic patients showing IgE to prohevein. The purified 36 kDa protein bound IgE from 6/29 (21%) latex-allergic sera, and the purified hevamine from only 1/29 patient sera. CONCLUSION: The observed high frequency of IgE antibodies to prohevein suggests that this protein is a major natural rubber latex allergen.
Adolescent↗
Purification and partial amino acid sequencing of a 27-kD natural rubber allergen recognized by latex-allergic children with spina bifida.
We purified from natural rubber latex (NRL) by means of high-performance liquid chromatography a 27-kD protein, recognized characteristically by IgE in sera from latex-allergic children with spina bifida or other congenital anomalies and histories of multiple surgeries. N-terminal sequence analysis of the purified 27-kD protein was unsuccessful suggesting that its N-terminus is blocked. To obtain internal sequence information from the protein it was digested with trypsin and the purified tryptic peptides were subjected to sequence analysis. Thirteen of the 14 sequenced peptides revealed no significant homology to any of the published protein sequences indicating that the 27-kD protein is previously undescribed at the primary structure level. However, one of the 14 sequenced peptides showed significant homology to the rubber elongation factor, a 14.6-kD NRL protein. For the time being, the 27-kD NRL protein is the first molecularly characterized NRL allergen associated with defined clinical manifestations of latex allergy.
Adolescent↗
Antibodies against oxidised low-density lipoprotein in juvenile chronic arthritis.
Enhanced lipid peroxidation, reported to take place in rheumatoid joints and suggested to play a significant role in joint inflammation, led us to study the occurrence of antibodies against oxidised low-density lipoprotein (Ox-LDL Ab) in patients with juvenile chronic arthritis. Enzyme-linked immunosorbent assay was used to detect Ox-LDL Ab and antiphospholipid antibodies (aPL Ab) in sera from 84 patients and 91 controls. Elevated levels of Ox-LDL Ab were found in 14 patients (17%) as opposed to 4 controls (4%; p < 0.01). Similarly, 14 patients had an elevated aPL Ab level and a fairly good correlation between Ox-LDL Ab and aPL Ab (r = 0.52) existed in the patients. The increased frequency of elevated levels of Ox-LDL Ab may reflect lipid peroxidation occurring in rheumatoid joints but crossreactivity with aPL Ab for the induction of Ox-LDL Ab cannot be excluded.
Adolescent↗
Predictive significance of rheumatoid factor.
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Arthritis, Rheumatoid↗
Antibody against oxidized low-density lipoprotein predicting myocardial infarction.
BACKGROUND: Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction. METHODS: Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay. RESULTS: The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P = .002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P = .005 for trend). CONCLUSIONS: Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.
Adult↗
Serum antibodies to oxidised low-density lipoprotein.
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Adolescent↗
Passive transfer of cutaneous mosquito-bite hypersensitivity by IgE anti-saliva antibodies.
BACKGROUND: Mosquito bites frequently cause cutaneous wheal and flare reactions, and recent immunoblotting studies have shown specific anti-saliva IgE antibodies in many persons who have such reactions. OBJECTIVE: The study was designed to show that human serum containing mosquito saliva-specific IgE antibodies can produce histamine release in vitro and whealing in vivo. METHODS: Two mosquito bite-tolerant subjects had bite challenges and Prausnitz-Küstner tests with heated and unheated serum from one patient with Aedes mosquito allergy. Immunoblotting and basophil histamine release tests were performed with the patient's and subjects' sera. RESULTS: Both mosquito bite-tolerant subjects had positive Prausnitz-Küstner reactions, which indicated a successful transfer of cutaneous mosquito hypersensitivity. The ordinary and passive basophil histamine release tests also produced positive results with Aedes communis antigens. CONCLUSION: The results of the Prausnitz-Küstner test, immunoblotting, and basophil histamine release tests are consistent with the hypothesis that mosquito bite whealing is mediated by specific anti-saliva IgE antibodies.
Animals↗
IgE immune response to rubber proteins in adult patients with latex allergy.
In the present immunoblot study we examined IgE immune responses to natural rubber latex proteins in sera from 27 adult patients with latex allergy. We demonstrated at least 30 proteins in the rubber tree sap, of which 19 bound IgE antibodies in a heterogeneous manner in patient sera. Twenty-two of the 27 patient sera (81%) showed positive immunoblot test results. IgE antibodies in the patient sera bound most frequently to a 20 kd allergen, which was recognized by 17 of the 22 (77%) patient sera with positive immunoblot test results. These results suggest that a 20 kd rubber protein could be a major allergen in adult patients with latex allergy. Immunoblotting with a representative set of allergens as antigen would offer a sensitive, confirmatory in vitro test to demonstrate hypersensitivity to latex.
Adult↗