Search

Fifty-one sera from patients with systemic lupus erythematosus (SLE) were studied in order to evaluate the prevalence of anticardiolipin (ACA) and anti-mitochondrial antibodies (AMA) type M5, and also to explore their relationship with the main serological and clinical features of the disease. A group of 25 (49.0%) patients was found to be ACA positive (IgG or IgG and IgM); in this group we found a significantly higher prevalence of false positive VDRL (p less than 0.01), lupus-like anticoagulant (p less than 0.05), and AMA type M5 (p less than 0.01), but not of anti-ds or ss-DNA antibodies. Three sera positive for ACA, AMA-M5 and anti ss-DNA were absorbed with cardiolipin liposomes. Anti-DNA and AMA-M5 showed only a minimal decrease. Central nervous system involvement and especially seizure syndrome was demonstrated with a higher prevalence in ACA-positive groups (p less than 0.05). Despite the results of absorption experiments, the close relationship between AMA-M5 and ACA, false positive VDRL or lupus-like anticoagulant (LLAC) might justify a speculation on the antiphospholipid nature of this antimitochondrial activity.

Twenty-eight subjects affected by perennial asthma were selected in order to investigate the possibility of inducing or relieving an asthmatic attack by means of suggestion. Twenty-five were positive to methacholine challenge test and, among them, eleven reacted to an ultrasonic nebulized distilled water test. The effect of suggestion on airway response was assessed by eight inhalations of normal saline at 32 degrees C alternately presented as a bronchoconstrictor or as a bronchodilator drug. Eight inhalations of the same diluent without any psychic stimulus were used as control test. Seven patients reacted with bronchoconstriction to both positive and negative suggestion and to control test. Further, this group of patients showed a lower methacholine PD20 when compared with the other subjects. In this study, the effects of suggestion on bronchial reactivity were not observed and bronchoconstriction belonged to an individual hyperreactivity of the airways.

Anti-endothelial cell antibodies (AECA) have been detected in 51 lupus sera by cell surface radioimmunoassay with a prevalence of 39·2% for IgG and 45·1% for IgM-AECA. No correlations were found between AECA and different clinical or laboratory parameters, including the presence of anti-cardiolipin antibodies and signs associated with the presence of anti-phospholipid antibodies. However, absorption with cardiolipin liposomes partially inhibited endothelial cell binding, and affinity purified anti-cardiolipin antibodies were able to react with intact human endothelial cells. The binding did not occur via Fc receptors since blocking of Fc receptors with rabbit IgG did not affect the endothelial cell reactivity. Taken together our findings support the hypothesis that antibodies directed against negatively charged phospholipids can be part of the anti-endothelial cell antibodies in certain lupus sera. The possible role of these cross-reacting antibodies in the pathogenesis of vascular thrombosis in lupus patients is discussed.

Sera from patients affected either by the classic/Mediterranean form (5 patients) and human immune deficiency virus (HIV)-associated (12 patients) form of Kaposi's sarcoma (KS) were compared in supporting endothelial cell in-vitro proliferation. Healthy blood donors (15) and a group of 7 HIV-positive drug addicts with no dermatological involvement were used as control groups. Endothelial cell growth was assessed by means of a [3H]thymidine incorporation and by an optical density direct cell-counting assay. Our results indicate that, at the highest concentrations, sera obtained from patients affected by KS with no sign of HIV infection induced significantly higher levels of endothelial cell proliferation when compared with HIV-associated KS and with normal controls. This growth-promoting activity was apparently cell selective, being present in endothelial cell but not in fibroblast cultures.

Anti-T3-induced T cell activation was standardized in human peripheral blood lymphocytes with respect to dose response, time kinetics and effect of exogenous IL-2 on blastogenesis and on IL-2 receptor expression, identified by anti-Tac monoclonal antibody. IL-2 was able to significantly increase 3H-thymidine uptake and Tac antigen expression in unstimulated and anti-T3 activated lymphocytes. This enhancement was more evident in cultures stimulated with non-mitogenic concentrations of anti-T3, supporting the hypothesis that these concentrations sensitize T cells to the Tac-inducing effects of IL-2. This model of lymphocyte activation was then applied to selected immunocompromized elderly subjects. The aged subjects showed depressed blastogenetic responses and Tac antigen expression, which were not corrected by prolonging the time of cultures. Aged lymphocytes showed a good response to costimulation with anti-T3 and IL-2, suggesting that at least for the anti-T3 activation pathway they are able to respond to IL-2 signals.

Con A induced suppressor cell assay was further characterized in this study. Significant lower mitogenic responses of autologous fresh cells cocultured with Con A-activated cells were found when compared with the response of cocultures of responders plus control cells preincubated in medium alone. However, Con A-activated cells did not express a real suppression, since no difference was found between responses of fresh responders alone and responses of cocultures with Con A-activated cells. So, Con A activation seemed to block the expression of the enhancement provided by control cells to autologous responders, rather than to induce a real suppressor activity. The induction of the Con A suppressor cell activity required cell proliferation but it was not proportional to the degree of DNA synthesis. Monocyte depleted cell populations exhibited lower Con A suppressor cell activity compared to unfractionated cells, suggesting a cooperative role of monocytes in the Con A induction step. The expression of this activity was not due to a cytotoxicity against the responders and was dependent on the number of activated cells added. Mononuclear cells from active lupus erythematosus (SLE) patients, but not from inactive SLE patients differed from normal controls in showing a significant loss of suppression index.

To determine the diagnostic value and precision of the quantitative skin test (QST), RAST, specific nasal (NPT) and conjunctival (CPT) provocation tests, we studied 91 patients, suffering from allergic rhinoconjunctivitis with positive skin prick tests (SPT) to common allergens, among whom sixty-nine of them had symptoms related to the positive SPT, and 22 had no clinical correspondence. In these two groups, by comparing the threshold of positivity, we investigated whether there was any parallelism between responses to the tests considered. We also compared the level of specific IgE (RAST) to the wheal-areas evoked by preliminary SPT for the corresponding allergen in order to detect any quantitative relationship between these investigations. Increasing concentrations of standardized allergen extracts (from 10 to 100,000 BU/ml) were used in all in vivo tests. NPT was evaluated on the basis of multiple recordings of nasal resistances by anterior passive rhinomanometry. QST proved to correlate well with RAST and its easier method ensures it a major role in assessing the levels of allergic sensitization. SPT wheal-areas and RAST vales correlated well only for grass and birch, presumably because of better standardization of these allergen extracts. When provocation tests, especially NPT, were positive, patients were almost always symptomatic for the allergen tested (high positive predictive value). Likewise, 21 out of the 22 asymptomatic subjects had negative NPT (high specificity). These results suggested the utility of standardized provocation tests in order to restrict diagnosis to the truly causative allergens in patients with multiple positive SPT results.

Peripheral blood mononuclear cells (PBMC) from 40 normal individuals, 20 men and 20 women, divided according to age were evaluated for their ability to mediate natural killer (NK) cytotoxicity, using the K562 erythroleukemic cells as target. The results of a specific 51Cr release assay demonstrated that NK activity was greater in men than in women. There was a significant correlation between NK activity and the percentages of Leu 11a+ cells in younger women, but not in the other groups and no correlation between NK activity and Leu 7+ cells.

In a series of 42 positive sera, anti-mitochondrial type M5 antibodies (AMA-M5) were found most frequently in patients with SLE (24) and SLE-like syndromes. Patients with AMA-M5 displayed a higher prevalence of thrombocytopenia, thrombosis, biological false positive seroreactions for syphilis, lupus-like anticoagulant activity and anti-cardiolipin antibodies in comparison with a group of 43 SLE AMA-M5 negative patients. The strong association between anti-phospholipid and AMA-M5 antibodies cannot be explained entirely by cross-reactivity between these two groups of antibodies, as indicated by absorption experiments and studies using affinity purified antibody preparations. However, cardiolipin liposomes were able to reduce partially the titres of AMA-M5 sera, suggesting that a small population of AMA-M5 antibodies exists that cross-reacts with cardiolipin. The existence of this population was further substantiated by our demonstration that an IgM monoclonal antibody, from a patient with Waldenström's macroglobulinaemia, displayed both anti-cardiolipin and AMA-M5 activity, and AMA-M5 activity was completely inhibited by cardiolipin.

The clinical and immunochemical classification of 166 patients with cryoglobulinemia are presented. 52% of the cryoglobulins were detected in patients hospitalized because of various causes. The most frequent association was with liver and lymphoproliferative diseases (in particular with Waldenström's macroglobulinemia); two thirds of the patients with liver diseases presented with a purpura-arthralgia syndrome, and the hepatic involvement was only brought to evidence by subsequent laboratory investigation. The presence of cryoglobulins did not usually interfere with the clinical course of the basic condition. In 79 patients the cryoglobulinemia was considered idiopathic. In order to study the natural course of the disease in the idiopathic cases, a group of 35 patients had been followed up for 8-17 years: 37% developed a membranous proliferative glomerulonephritis, and more than half died of renal insufficiency; in 11% cirrhosis was diagnosed after a period of 4-9 years; another 11% developed a lymphoproliferative disease; of the remaining 40%, 2 are still asymptomatic, and the others are affected by purpura-arthralgia syndrome.

The detection of specific IgE antibodies to environmental allergens does not always coincide with a diagnosis of clinically evident allergic disease, because some patients with positive skin and/or in vitro test results have no symptoms related to the allergen or allergens that induced the antibodies.In a multicenter study the optimal cutoff values for specific IgE antibody levels and skin test results that could discriminate between patients with symptomatic and those with asymptomatic allergy were determined.IgE antibodies specific for a panel of common aeroallergens were assayed with the Pharmacia CAP System (Pharmacia, Uppsala, Sweden) in two groups of patients, a group of 267 patients with symptomatic allergy and a group of 232 with asymptomatic allergy--both with positive skin prick test results--and in a group of 243 healthy, nonallergic control subjects. The cutoff values were established by receiver operating characteristic analysis.A significantly higher mean specific IgE antibody value was found in patients with symptomatic allergy compared with patients with asymptomatic allergy (p0.001) and in patients with symptomatic allergy compared with healthy control subjects (p0.001). The optimal CAP System cutoff value between patients with symptomatic and those with asymptomatic allergy was 11.7 kU/L, and when seasonal allergens were compared with perennial allergens, the cutoffs were 10.7 kU/L and 8.4 kU/L, respectively. The optimal cutoff value for the skin prick test was a wheel area of 32 mm2 for seasonal allergens and 31 mm2 for perennial allergens. The skin test had a lower diagnostic value (sum of sensitivity and specificity) than the CAP System.Cutoff values for specific serum IgE antibody levels are likely to be useful in clinical practice to distinguish symptomatic from asymptomatic allergy in patients with positive skin test results.

Thirty-one AIDS patients were typed for HLA A, B, C, and DR antigens. We confirmed that frequency of B35 is significantly higher in patients than in controls. No significant frequency differences in other HLA antigens were found. The analysis of HLA distribution in AIDS patients by risk categories suggests that B35 is a major risk factor, primarily mainly for patients belonging to the category of intravenous (IV) drug addicts.

HLA phenotype distribution was investigated in 91 affective patients. Significant increases over those of the control population were found in HLA-A 29 and in Bw 22 frequencies, while A 10 and A 30 were decreased. No significant difference was shown between the two clinical subgroups (41 unipolar patients and 50 bipolar ones). On comparing our data with those from other authors, Bw 16 was significantly increased. However, a high degree of heterogeneity was also shown for this antigen. Of some interest is the finding that relapsed and non-relapsed patients during long-term lithium therapy display diverging HLA phenotype distributions, with B 5 increased among the non-relapsed subjects.