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Biomedical subjects

P Riboldi

Publications and source records attributed to P Riboldi.

At least 19 recordsLinked to original sources

Measurement of electrical skin impedance of dermal-visceral zones as a diagnostic tool for disorders of the immune system.

Among complementary medicine approaches, diagnostic screening tools based on neuroreflexology have been recently developed. Such techniques are based on the rationale that measurement of electrical impedance of specific dermal zones might reflect the occurrence of pathological states in the corresponding internal organs or systems. Our objective was to evaluate the reliability of a neuroreflexology-based diagnostic test in diagnosing immune-mediated diseases in a blinded single centre study. Seventy-eight patients with immune-mediated diseases (38 patients with autoimmune diseases (AD), and 40 allergic patients) were included in the study. Thirty age and sex matched healthy subjects were also evaluated as a control group. All the patients and subjects underwent conventional medical history and physical examination. We evaluated a device manufactured by Medex Screen Ltd (Arad, Israel). The Medex Test analysis was carried out by a second physician who was blinded to the previous diagnosis. A high correlation between the formal clinical diagnosis and the results of the measurement of electrical skin impedance was reported, with a specificity of 93.3% and a sensitivity of 81.2%. Both sensitivity and specificity dropped when analysing the autoimmune and the allergic group separately, but remained significant for the autoimmune diseases. Degree of activity of the allergic disorders, or specific treatment, did not affect the diagnostic properties of the described device. The Medex Test neurophysiology based technique has the potential to serve as a diagnostic tool for immune based pathologies. Future studies will define this tool place in routine evaluation and potential screening ability.

Adult↗

Nonorgan specific autoantibodies and heart damage.

Heart damage, mediated by different autoantibodies can involve several anatomical heart structures: valves, arteries, conduction tissue. Verrucous endocarditis is frequently reported in patients with antiphospholipid syndrome (APS) with or without systemic lupus erythematosus (SLE), particularly if they suffer from central nervous system involvement. Antiphospholipid antibodies (aPL) were shown deposited at subendothelial level of the affected valves. According to several in vitro and in vivo experimental models, aPL, anti-oxidized LDL (oxLDL), anti-heat shock protein 65 (HSP65) and anti-endothelial cells antibodies (AECA) seem to be involved in the pathogenesis of the atherosclerosis phenomena described in systemic autoimmune disease and vasculitis. However, the observation of the association of the same antibodies with clinical and subclinical atherosclerosis in patients is still controversial. The children of anti-Ro/SSA positive mothers can be affected by the congenital heart block. Anti Ro/SS-A antibodies play a major pathogenic role in affecting the heart conduction tissue in this rare condition.

Animals↗

Statins and autoimmune diseases.

Besides the well-known lipid-lowering effect, statins display nonlipid-lowering pharmacological activities. In vitro and in vivo studies suggest that statins have direct anti-inflammatory, anti-thrombotic and plaque-stabilizing effects via a number of mechanisms. A direct immunomodulatory effect has been also demonstrated in in vitro and in vivo experimental models. In addition to traditional risk factors, systemic inflammation, immune-mediated responses and thrombophilia have been suggested to play a major role in sustaining the premature atherosclerosis in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. This review focuses on the anti-inflammatory and immunomodulating mechanisms of statins as demonstrated in in vitro and in vivo experimental models, providing new insights for the use of statins in treating systemic autoimmune diseases both for their anti-atherosclerotic activity and for their pleiotropic effects on inflammation, haemostasis and the immune responses.

Animals↗

Prevalence of autoantibodies against structure specific recognition protein 1 in systemic lupus erythematosus.

Antibodies (Abs) against the structure specific recognition protein 1 (SSRP1) were reported in a small systemic lupus erythematosus (SLE) series but not in other systemic autoimmune diseases. The aim of the study was to confirm the selective presence of anti-SSRP1 Abs in a larger SLE series and to evaluate their relationship with disease activity and other immune markers. Anti-SSRP1 Abs were investigated by a 'home made' ELISA in: 120 SLE, 65 rheumatoid arthritis (RA), 51 systemic sclerosis (SSc), 23 Churg-Strauss syndrome (CSS) and 40 idiopathic autoimmune urticaria (IAU) patients and 190 healthy controls. Sera from MRL lpr/lpr and Balb-c mice were also tested. Anti-SSRP1 Abs were detected in 43 SLE (35.8%), nine SSc (17.6%), eight RA (12.3%), six IAU (15%), three CSS (13%) patients and five healthy controls (2.6%). Antibody prevalence and titers were significantly higher in SLE patients than in sera from both normal and disease controls. Anti-SSRP1 Ab activity was also detected in sera from MRL lpr/lpr but not Balb-c mice. The antibodies did not correlate with the disease activity evaluated as the ECLAM index score and were more prevalent in patients without renal involvement. No correlation was found with other serum autoantibodies. Our results confirm that anti-SSRP1 Abs are associated with but not specific for the lupus disease.

Adolescent↗

Pathogenic mechanisms mediating antiphospholipid syndrome.

Antiphospholipid antibodies are the marker for antiphospholipid syndrome. There is evidence that these autoantibodies lead to both thrombotic diathesis and obstetrical manifestations. Besides the known interaction with soluble coagulation factors, in vitro and in vivo experimental models and studies in humans recently have shown the ability of antiphospholipid antibodies to modulate functions of cells involved in coagulation homeostasis. These findings support a new hypothesis to explain the paradox of the prolongation of coagulation assays in vitro and the association with thrombophilic diathesis in vivo. Obstetrical manifestations have been linked to a direct antibody effect on the trophoblast leading to defective placentation that is not necessarily associated with thrombotic phenomena. Phospholipid binding proteins such as beta 2 -glycoprotein I appear to behave as a bridge between circulating antiphospholipid antibodies and cellular targets.

Animals↗

Cellular origin, antigen reactivity, and VH segment structure of IgM mAbs from AIDS lymphomas.

In the present studies we analyzed the Ag specificity, VH gene structure, and cellular origin of three IgM mAb-producing cell lines established in vitro from bioptic specimens of three AIDS patients with BL. We found that (i) both HBL-2 and HBL-3 IgM mAbs were cold agglutinins highly specific for the i blood group determinant, a self Ag the expression of which is dominant in the early stages of life, and both mAbs used somatically point-mutated VH 4-21 segments; (ii) HBL-1 IgM mAb, the Ag-specificity of which has not been determined, used a putatively mutated member of the VHIII family; and (iii) both HBL-1 and HBL-2, but not HBL-3, cells expressed CD5 mRNA, suggesting a B-1 cell origin. The utilization of VH4-21 by the HBL-2 and HBL-3 cold agglutinins is consistent with the usage of this gene segment by all the reported pathogenic except the naturally occurring cold agglutinins. This restricted VH gene usage may reflect an inherent affinity of the germline VH4-21 gene product for the i/I carbohydrate structure, and, perhaps, an overrepresentation of VH4-21 in the human early and late B-cell repertoire. Consistent with both an early and late developmental expression of the VH4-21 gene is the B-1 and B-2 cellular origin of the two VH4-21+ cold agglutinins reported here. Thus, the two cold agglutinin autoantibodies possibly emerged at different stages of the natural history of the B-cell repertoires of these patients and might display a different temporal relationship, as discussed below, to the time of emergence of the respective tumoral cells. The somatically mutated status of the HBL-2 and HBL-3 mAb VH segments was suggested by the monomorphism of the human VH4-21 gene, the extension of the nucleotide differences to the, in general, highly conserved JH segment; and it was formally proved in HBL-3 mAb. Positive selection by Ag of the R mutations in the HBL-2 and HBL-3 mAb VH segments was suggested by the differential R:S mutation ratios in the CDRs and FRs (HBL-2 mAb, 5.0 and 1.1, respectively; HBL-3 mAb, 2.2 and 0.3, respectively) but not substantiated by appropriate statistical analysis according to the binomial distribution model.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Two acquired immunodeficiency syndrome-associated Burkitt's lymphomas produce specific anti-i IgM cold agglutinins using somatically mutated VH4-21 segments.

We analyzed the reactivity and the structure of the VH and VL segments of two IgM monoclonal antibodies (MoAbs) produced by spontaneously in vitro outgrowing cell lines, HBL-2 and HBL-3, established from two acquired immunodeficiency syndrome (AIDS) patients with Epstein-Barr virus (EBV)-negative Burkitt's lymphoma (BL). These B-cell clones were representative of the respective neoplastic parental clones, as determined by immunophenotypic and molecular genetic analysis. The IgM MoAbs were highly specific for the i determinant on red blood cells (cold agglutinins), but bound none of the other eight self and nine foreign antigens (Ags) tested, including those most commonly recognized by natural antibodies or autoantibodies. Structural analysis showed that the IgM MoAb VH segment sequences were 93.5% and 84.2% identical with that of the germline VH4-21 gene, which encodes the vast majority of cold agglutinins that are specific for the i/l carbohydrate Ag and are produced under chronic lymphoproliferative conditions. The HBL-2 MoAb VH4-21 gene segment was juxtaposed with 20P3 and JH6 genes and paired with a V lambda 1 segment, the sequence of which was 95.5% identical to that of the germline Humlv117 gene; the HBL-3 MoAb VH4-21 gene segment was juxtaposed with DXP'1 and JH5 genes and paired with a V lambda 1 segment, the sequence of which was 86.7% identical to that of the germline Humlv1L1 gene. The high degree of conservation of the VH4-21 gene in the human population, the nature of the nucleotide differences in the expressed VH4-21 segments, and the presence of nucleotide substitutions in the HBL-2 and HBL-3 IgM MoAb JH and/or J lambda segments suggested that the MoAb V segments underwent a process of somatic hypermutation. This was formally shown in the HBL-3 MoAb VH segment, by differentially targeted polymerase chain reaction amplification of the HBL-3 MoAb-producing cell genomic DNA. In addition, cloning and sequencing of the genomic DNA from fibroblasts of the same patient whose neoplastic B cells gave rise to the HBL-3 cell line yielded a germline copy of the VH4-21 gene. Thus, the expression of VH4-21 gene products may be involved in a self Ag-driven process of clonal B-cell expansion and selection associated with BL in these AIDS patients.

Agglutinins↗

Relationship between antibodies to dsDNA and to soluble cellular antigens and histologically defined glomerulonephritis in patients with SLE.

To better define the relationships between circulating autoantibodies and renal involvement in systemic lupus erythematosus (SLE), antibodies to both dsDNA and soluble cellular antigens were detected in sera from a large series of SLE patients. Significantly higher dsDNA binding activities and lower complement levels at onset were found in patients with renal disease; however, this was uniquely due to subjects with diffuse or focal proliferative glomerulonephritis. Patients with membranous nephropathy (MGN) showed very low dsDNA binding activities (6/9 of them being negative for dsDNA antibodies) and normal mean C3 and C4 levels. A comparison between patients with proliferative nephritis and patients without renal involvement with high dsDNA binding activities revealed significantly lower complement levels in the former group. No significant difference was observed in the prevalence of antibodies to soluble cellular antigens between patients with or without renal disease; however, nRNP antibody was two-fold more frequent in patients with MGN than in all other subgroups. This study highlights the close relationship between concurrently high anti-dsDNA and low complement levels and proliferative glomerulonephritis in SLE, and suggests that subjects with MGN may represent a subgroup of SLE patients showing peculiar serological features. Different mechanisms possibly involved in the pathogenesis of MGN in SLE are discussed.

Adolescent↗

The clinical significance of autoantibodies to soluble cellular antigens in systemic lupus erythematosus.

The relationships between autoantibodies to soluble cellular antigens and clinical features in systemic lupus erythematosus (SLE) were investigated in a large clinical-serological study. The absence of these precipitins in serum was associated with a low prevalence of vasculitis and membranous nephropathy (MGN). Other significant findings were the associations between nRNP antibody and Raynaud's phenomenon and MGN, SSB antibody and sicca complex, PCNA antibody and a young age at onset, and Bu antibody and an old age at onset. However, the most impressive findings were in DA1-positive patients which showed a unique prevalence of photosensitive skin lesions, lymphoadenopathy and hepatosplenomegaly. The present study confirms the usefulness of antibodies to soluble cellular antigens in the classification of patients with SLE.

Adolescent↗

Clinical findings in patients with SLE whose sera contain antibodies to ribosomal ribonucleoprotein.

In a clinical and serological study performed on a large series of patients with different connective tissue diseases, anti-ribosomal ribonucleoprotein (rRNP) antibodies were detected only in a small proportion of sera with systemic lupus erythematosus (SLE). SLE patients positive for anti-rRNP autoantibodies showed a significantly higher incidence of hemolytic anemia. The reasons for this surprising association are still unclear; however, this finding suggests that rRNP precipitin might be considered as a useful marker of a particular subgroup of patients with SLE.

Anemia, Hemolytic, Autoimmune↗

Anti-Epstein-Barr virus antibodies in systemic lupus erythematosus.

Sera from 18 patients with Systemic Lupus Erythematosus (SLE), 20 with nonA-nonB acute hepatitis and 19 healthy subjects were tested for the presence of antibodies to the viral capside of Epstein-Barr virus. In patients with SLE the mean titre of anti-VCA IgG was significantly higher than in normal subjects (p less than 0.02), and the percentage of patients with titres greater than 1:160 was significantly higher than in normal population (p less than 0.01). These high anti-VCA) titres in SLE patients are probably related to a defective immune surveillance.

Adolescent↗

Antibodies to Epstein-Barr virus and cytomegalovirus in primary Sjogren's syndrome.

Sera from 28 patients with Primary Sjögren's Syndrome (SS) and 20 healthy subjects were tested for the presence of antibodies to Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV). No difference was noted in the mean titre of anti-CMV antibodies in patients and in controls. For what concerns EBV, the mean titre of anti-EBNA antibodies was significantly higher in SS patients than in normals (p less than 0.001); moreover, within the SS population, titres were higher in SSB-positive than in SSB-negative patients (p less than 0.05). These results, together with the fact that anti-SSB antibodies (characteristic of Sjögren's Syndrome) recognize also two EBV-encoded RNAs, strengthen the hypothesis that EBV is involved in the pathogenesis of SS.

Adult↗

Comparison between counterimmunoelectrophoresis and double radial immunodiffusion in the detection of antibodies to topoisomerase I in sera from scleroderma patients.

Sera from 146 patients with progressive systemic sclerosis have been submitted to the detection of anti-Scl 70 antibodies by both double radial immunodiffusion (ID) and counterimmunoelectrophoresis (CIE). CIE detected a significantly higher number of positive sera from patients with diffuse scleroderma, while no difference between the two techniques was noted in sera from patients with CREST variant. CIE increases the diagnostic importance of the serologic investigation in systemic sclerosis and gains a better distinction between subgroups of patients with different clinical expressions of this disease.

Autoantigens↗

Detection of two associated precipitating autoantibodies (DA1 and DA2) in sera from patients with systemic lupus erythematosus.

In a clinical and serological study performed on a large series of patients with different connective tissue disorders, only sera from patients with systemic lupus erythematosus (SLE) contained two precipitin systems (DA1 and DA2) directed against nuclear proteins present in a total extract of human spleen. DA1 antibody appeared in 5% of SLE patients and was always associated with DA2 antibody which was found in about 22% of SLE patients. Sera monospecific for DA1 and DA2 antibodies gave a speckled staining pattern on both rat kidney and HEp2 cells. DA1-positive patients showed a higher incidence of photosensitivity (p less than 0.001), hepatosplenomegaly (p less than 0.001), hemolytic anemia (p less than 0.05), CNS involvement, vasculitis, and diffuse proliferative glomerulonephritis than DA1-negative ones. DA2-positive patients showed an increased incidence of leukopenia (p less than 0.05) and thrombocytopenia (p less than 0.01) than controls. While several indirect evidences suggest that DA1 precipitin might be identical to the previously described MA antibody, DA2 precipitin appears as a new system in SLE. The serological association between DA1 and DA2 antibodies might be analogous to the well known ones between antibodies to Sm and nRNP and to SSA/Ro and SSB/La.

Antibodies, Antinuclear↗

Detection of circulating DNA in plasma of patients with pulmonary embolism by counterimmunoelectrophoresis.

In order to confirm the usefulness of free plasma DNA detection in the diagnosis of pulmonary embolism (PE), we have studied 16 patients with PE, 33 with various diseases, and 13 normal subjects. Free plasma DNA was detectable in 15 of 16 patients with PE (94%) and in 3 control patients, but never in plasma from normal subjects. In most cases, DNA was detectable until the 10th day after PE. In conclusion, counterimmunoelectrophoresis is a rapid, inexpensive and specific test which may be used as an exclusion test in the detection of patients suspected of having PE, who will have to undergo more extensive evaluation.

Counterimmunoelectrophoresis↗

Autoantibody to proliferating cell nuclear antigen (PCNA) in SLE: a clinical and serological study.

In a clinical and serological follow-up study on a large series of subjects with different connective tissue disorders, anti-PCNA/cyclin autoantibodies were found in about 3% of patients with SLE. Positive subjects showed a higher incidence of diffuse proliferative glomerulonephritis and hematological disorders than the general SLE population. A highly significant serological association between PCNA and SL/Ki autoantibodies (p less than 0.001) has been observed. Persistence or disappearance of serum PCNA antibodies were independent of any clinical and serological feature or the therapeutic regimen employed.

Adolescent↗