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R Rolla

Publications and source records attributed to R Rolla.

7 recordsLinked to original sources

Circulating antibodies recognizing malondialdehyde-modified proteins in healthy subjects.

Antibodies against malondialdehyde (MDA)-modified proteins are often increased in patients with diseases related to oxidative stress. However, the clinical significance of these antibodies is hampered by their frequent presence also in healthy controls. Aim of this work has been to characterize the immune reactivity against MDA-derived antigens in healthy subjects. The sera of 120 healthy subjects contained IgG and IgM targeting MDA-modified human albumin (HSA), fibrinogen, and LDL. These sera also displayed weak reactivity with oxidized LDL and HSA complexed with oxidized arachidonic acid. Conversely, oxidized HSA or HSA complexed with other aldehydic lipid peroxidation products was not recognized. Control sera also did not recognize cyclic dihydropyridine-MDA products, while HSA-MDA reactivity was associated (r > 0.9; p <.0005) with the presence of fluorescent lysine-conjugated-imine cross-links. In Western blots both IgG and IgM recognized high molecular weight HSA-MDA aggregates, but not monomeric HSA-MDA adducts. The addition of sodium cyanoborohydride, that prevented conjugated-imine fluorescence and protein aggregation during HSA-MDA preparation, abolished the antibody binding. This suggested that the plasma of healthy subjects contained IgG and IgM recognizing protein aggregates linked through 1-amino-3-imino-propene bridges. The function of these antibodies is at the moment unknown, but they might contribute to scavenging MDA cross-linked proteins.

Adult↗

Antiphospholipid antibodies associated with alcoholic liver disease specifically recognise oxidised phospholipids.

BACKGROUND: Circulating antiphospholipid antibodies (aPL) are often detected in patients with alcoholic liver disease (ALD) but little is known about the causes of their formation. AIMS: We have evaluated whether ethanol mediated oxidative injury might promote the development of aPL in ALD. PATIENTS AND METHODS: IgG against beta(2) glycoprotein 1 (beta(2)-GP1), cardiolipin, and human serum albumin (HSA) complexed with either oxidised arachidonic acid (HSA-APP) or malondialdehyde (HSA-MDA) were assayed by ELISA in heavy drinkers with or without ALD and in healthy subjects. RESULTS: Circulating IgG recognising cardiolipin were significantly higher in ALD patients than in controls. However, anticardiolipin reactivity of ALD sera was only evident using, as the antigen, oxidised cardiolipin but not oxidation protected cardiolipin. In ALD patients, individual values of IgG antioxidised cardiolipin were associated with the titres of antibodies against HSA-MDA and HSA-APP (r=0.68 and 0.72, respectively; p<0.0001) used as markers of oxidative stress. ALD patients also displayed increased levels of antibodies against phospholipid binding protein beta(2)-GP1, and individual reactivity towards oxidised cardiolipin and beta(2)-GP1 were highly correlated (r=0.85; p<0.0001). IgG binding to oxidised cardiolipin, HSA-MDA, and HSA-APP was also significantly higher in beta(2)-GP1 positive than in beta(2)-GP1 negative sera. However, preadsorption of beta(2)-GP1 positive sera on beta(2)-GP1 coated ELISA plates reduced reactivity to oxidised cardiolipin by 80%, without affecting that to HSA-APP or HSA-MDA. CONCLUSIONS: Ethanol induced oxidative injury is associated with the development of antibodies targeting complexes between oxidised cardiolipin and beta(2)-GP1. These antibodies might account for high aPL titres observed in patients with severe ALD.

Adult↗

Antibodies against advanced glycation end product Nepsilon-(carboxymethyl)lysine in healthy controls and diabetic patients.

AIMS/HYPOTHESIS: Nepsilon-(carboxymethyl)lysine (CML) is one of the end products of protein glycoxidation and its accumulation is associated with diabetes complications. Since CML-modified proteins are immunogenic, we have investigated the presence of anti-CML antibodies in diabetic patients. METHODS: Antibodies against CML-modified human serum albumin (HSA) were measured by direct enzyme-linked immunosorbent assay in the sera from 289 non-selected diabetic and in 120 healthy control subjects. RESULTS: Immunoglobulin-G reactivity towards CML-HSA was significantly higher in diabetic than in control sera. The presence of anti-CML IgG in diabetics, however, was not influenced by age, duration of disease or glycaemic control. Analysis of distribution frequency revealed that anti-CML IgG in both control and diabetic subjects were not normally distributed and that the distribution curves were similar in the two groups. Moreover, only 14% of the diabetic subjects displayed antibody binding to CML-HSA above 95 centile in the control cohort. Competition experiments confirmed that the IgG detected in both control and diabetic groups were specific for CML epitopes and did not recognise glycated-HSA in which CML formation was inhibited. CONCLUSION/INTERPRETATION: The presence of anti-CML IgG in diabetic sera is probably not related to the development of an immune response against protein glycoxidation products.

Adult↗

Detection of circulating antibodies against malondialdehyde-acetaldehyde adducts in patients with alcohol-induced liver disease.

Acetaldehyde and malonildialdehyde can form hybrid protein adducts, named MAA adducts that have strong immunogenic properties. The formation of MAA adducts in the liver of chronic alcohol-fed rats is associated with the development of circulating antibodies that specifically recognized these adducts. The aim of this study was to examine whether MAA adducts might participate in the immune response associated with human alcohol-induced liver disease. Circulating antibodies against MAA adducts were evaluated in 50 patients with alcohol-induced hepatitis or cirrhosis, in 40 patients with non-alcohol-induced liver disease, in 15 heavy drinkers without liver damage and in 40 healthy controls by enzyme-linked immunosorbent assays (ELISA). Immunoglobulin G (IgG) reacting with MAA-modified proteins were significantly increased in the patients with alcohol-induced cirrhosis or hepatitis. The individual levels of anti-MAA IgG in those patients were associated with the severity of liver damage. Anti-MAA antibodies were also positively correlated with the levels of IgG recognizing epitopes generated by acetaldehyde and malonildialdehyde. However, competitive inhibition experiments indicated that the anti-MAA antibodies were unrelated to those against acetaldehyde- or malonildialdehyde-derived antigens and mainly recognized a specific, cyclic MAA epitope. Some degree of immune reactivity towards MAA adducts was also observed in patients with non-alcohol-induced liver injury. However, competitive ELISA showed that the antigens recognized by these sera were not the cyclic MAA adducts. Altogether, these results showed the formation of MAA antigens during alcohol-induced liver disease and suggest their possible contribution to the development of immunologic reactions associated with alcohol-related liver damage.

Acetaldehyde↗

[Immunoglobulin classes: M, A, G in blood serum of patients with mumps].

The levels of immunoglobulins of: M, A, G classes in 65 patients (11 women and 54 men) ill from epidemic parotitis, at acute phase and after subsidence of symptoms, were determined. The results of examinations were considered in two categories. One of them concerned all the patients, the other one comprised the patients with three groups of complications: meningitis, orchitis and joint occurrence of meningitis and orchitis. No deviations from the norm were found in IgM and IgA levels, both in acute phase and during convalescence. An increase of IgG content was observed only in the initial phase of epidemic parotitis. Taking into consideration the complications during the disease there was obtained an increase of IgM level in the patients with joint occurrence of meningitis and orchitis only in acute phase. Increased IgG values in the course of mumps concerned the patients with meningitis and orchitis and could be still observed after subsidence of the symptoms of the disease.

Adolescent↗