Are the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and the undifferentiated connective tissue disease (UCTD) related to each other? A case-control study of environmental exposures.

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is an entity that includes different autoimmune conditions observed after exposure to an adjuvant. Patients with undifferentiated connective tissue disease (UCTD) present many signs and symptoms of ASIA, alluding to the idea that an exposure to adjuvants can be a trigger also for UCTD. The aim of this case-control study was to investigate exposure to adjuvants prior to disease onset in patients affected by UCTD. Ninety-two UCTD patients and 92 age- and sex-matched controls with no malignancy, chronic infections, autoimmune disease nor family history of autoimmune diseases were investigated for exposure to adjuvants. An ad hoc-created questionnaire exploring the exposure to vaccinations, foreign materials and environmental and occupational exposures was administered to both cases and controls. Autoantibodies were also analyzed (anti-nuclear, anti-extractable nuclear antigens, anti-double-stranded DNA, anti-cardiolipin, anti-ß2 glycoprotein I). UCTD patients displayed a greater exposure to HBV (p = 0.018) and tetanus toxoid (p < 0.001) vaccinations, metal implants (p < 0.001), cigarette smoking (p = 0.006) and pollution due to metallurgic factories and foundries (p = 0.048) as compared to controls. UCTD patients exposed to major ASIA triggers (vaccinations, silicone implants) (n = 49) presented more frequently with chronic fatigue (p < 0.001), general weakness (p = 0.011), irritable bowel syndrome (p = 0.033) and a family history for autoimmunity (p = 0.018) in comparison to non-exposed UCTDs. ASIA and UCTD can be considered as related entities in the "mosaic of autoimmunity": the genetic predisposition and the environmental exposure to adjuvants elicit a common clinical phenotype characterized by signs and symptoms of systemic autoimmunity.

The inter-observer reading variability in anti-nuclear antibodies indirect (ANA) immunofluorescence test: A multicenter evaluation and a review of the literature.

Recently there has been an increase demand for Computer-Aided Diagnosis (CAD) tools to support clinicians in the field of Indirect ImmunoFluorescence (IIF), as the novel digital imaging reading approach can help to overcome the reader subjectivity. Nevertheless, a large multicenter evaluation of the inter-observer reading variability in this field is still missing. This work fills this gap as we evaluated 556 consecutive samples, for a total of 1679 images, collected in three laboratories with IIF expertise using HEp-2 cell substrate (MBL) at 1:80 screening dilution according to conventional procedures. In each laboratory, the images were blindly classified by two experts into three intensity classes: positive, negative, and weak positive. Positive and weak positive ANA-IIF results were categorized by the predominant fluorescence pattern among six main classes. Data were pairwise analyzed and the inter-observer reading variability was measured by Cohen's kappa test, revealing a pairwise agreement little further away than substantial both for fluorescence intensity and for staining pattern recognition (k=0.602 and k=0.627, respectively). We also noticed that the inter-observer reading variability decreases when it is measured with respect to a gold standard classification computed on the basis of labels assigned by the three laboratories. These data show that laboratory agreement improves using digital images and comparing each single human evaluation to potential reference data, suggesting that a solid gold standard is essential to properly make use of CAD systems in routine work lab.

[IgE-mediated allergy to ethylene oxide in hemodialyzed patients]. / Allergia IgE-mediata verso l'ossido di etilene nei pazienti emodializzati.

Ethylene oxide (ETO) is widely employed in sterilization of hemodialysis materials. Many studies have shown that ETO may act as an antigenic compound when bound to human albumin, therefore eliciting allergic reactions during hemodialysis. In the present study, we investigated in 93 patients undergoing long-term hemodialysis the prevalence of sensitization to ETO. All the patients were investigated for the presence of allergic or pseudo allergic reactions during the treatment. Specific IgE to ETO were found in sera of 3 patients: 1 suffered from urticaria and 1 from glottic edema and hypotension during the dialysis. The third one had non symptoms. The employ of a gamma-rays sterilized filter determined the disappearance of clinical manifestations in the two symptomatic patients, therefore suggesting a pathogenetic role of the specific IgE to ETO in determining the clinical manifestations.

[Evaluation of a new multi-RAST method in the screening of allergy to inhalants]. / Valutazione di un nuovo metodo multirast nello screening dell'allergia da inalanti.

Sera from 1040 adult patients were tested by a new multi-RAST test and PRIST to determine the efficiency of each test in a screening for allergy to inhalants. The patients had been referred to our Institutions for allergological evaluation of respiratory diseases. All the patients had been thoroughly investigated by clinical history, skin prick test and RAST. In 505 a diagnosis of respiratory allergy to one or more inhalants allergens was established, while in 535 a diagnosis of atopy was not confirmed. The new multiRAST test consented to correctly detect 464 out of 505 atopic patients (efficiency 92%) and 517 out of 535 non atopic patients (efficiency 97%). PRIST showed in both cases a minor efficiency (71% in detecting atopy and 77% in detecting non atopy).

Is celiac disease associated with Alzheimer's disease?

An increased prevalence of celiac disease has been reported in neurological disorders of unknown etiology. A large proportion of Alzheimer's cases is still of unexplained etiology. Thirty-three Alzheimer's patients and 24 elderly controls were screened for celiac disease. IgA and IgG antigliadin antibodies were assayed in serum samples with enzyme-linked immunoassay. Confirmation of celiac disease in positive subjects was made by assaying IgA anti-endomysium antibodies by indirect immunofluorescence. Two Alzheimer's patients and 2 controls were positive for antigliadin antibodies (6 versus 8%; NS). None was positive for anti-endomysium antibodies. We conclude that the prevalence of celiac disease in Alzheimer's disease is not higher than in cognitively unimpaired elders, suggesting that the immune changes in celiac disease are unlikely to play a role in Alzheimer's disease.

[Sensitization against Parietaria pollen in a group of 1143 patients in the Brescian area]. / Sensibilizzazione verso il polline di Parietaria in una casistica di 1143 pazienti dell'area Bresciana.

1143 patients were selected among atopic outpatients followed up at our Institution (Clinical Immunology-University of Brescia) on the basis of documented sensitization to one or more inhalant allergens. All patients had been investigated by skin prick tests employing a large panel of allergens. Specific sensitization had been confirmed by clinical history and when necessary by RAST. The patients were investigated retrospectively for the prevalence of sensitization to Paretaria. 880 patients were sensitized to one or more pollens and among these 427 (48.5) to Parietaria. Among pollen monosensitized patients (with no concomitant allergy to other inhalants), 222 were sensitized to Graminacee and 125 to Parietaria. In these groups there was no difference in prevalence of asthma. Our study thereby shows that the prevalence of sensitization to Parietaria in Brescia is higher than described in other cities in North Italy. Our findings are supported by pollen concentration in atmosphere as determined by Burkard pollen trap.

[Sensitization to ethylene oxide: a possible cause of reactions in hemodialysis patients]. / Sensibilizzazione verso l'ossido di etilene: una possibile causa di reazioni nei pazienti in emodialisi.

147 hemodialyzed patient were studied for the presence of allergic reactions related to the dialytic treatment. Total IgE and specific IgE to common inhalants, ethylene oxide and phthalic anhydride were determined in all patients. The same determinations were also performed in two control groups. Specific IgE to ethylene oxide were detected in 7 sera. Among these 6 had a high total IgE level and 2 had a positive Phadiatop. Only 3 among the 7 positive patients had adverse reactions related to the hemodialysis (one suffered from itching, one from urticaria and the third from angioedema and hypotension). The resolution of the symptoms was obtained utilizing a gamma-rays sterilized filter. Therefore ethylene oxide sensitization may be a cause of some problems during hemodialysis. We couldn't find a relationship between atopic status and sensitization to ethylene oxide in as much in only 2 out of 7 patients sensitized to ethylene oxide, specific IgE to common inhalants were detected.