Characterization of immune cell phenotypes in adults with autism spectrum disorders.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impairments in verbal and non-verbal communication, impaired social interactions and repetitive behaviors. There is evidence of a link between ASD symptoms and immune dysfunction, but few studies have been performed in adult patients to confirm this. In this work, we used flow cytometry to study immunological differences in peripheral blood mononuclear cells from 59 adult patients and 26 healthy control subjects to identify possible immune cell profiles related with this group of disorders. We analyzed six immune cell subpopulations (ie, B-cells, CD4(+) and CD8(+) T-cells, NK, NKT cells, and monocytes) and their corresponding stages of apoptosis and activation. The most noteworthy results showed that, compared to healthy controls, patients had increased percentages of CD8(+) T-cells and B-cells, and a decrease in the percentage of NKT cells. Regarding CD25 expression, we found overall CD25(+) overexpression, primarily in NK and NKT cells. Apoptosis percentage showed an increasing trend only in monocytes of patients. These data support a link between ASD and immune dysfunction, suggesting that specific cellular phenotypes and/or activation status of immune cells may be relevant in adult ASD.

Therapeutic targets for olive pollen allergy defined by gene markers modulated by Ole e 1-derived peptides.

Two regions of Ole e 1, the major olive-pollen allergen, have been characterized as T-cell epitopes, one as immunodominant region (aa91-130) and the other, as mainly recognized by non-allergic subjects (aa10-31). This report tries to characterize the specific relevance of these epitopes in the allergic response to olive pollen by analyzing the secreted cytokines and the gene expression profiles induced after specific stimulation of peripheral blood mononuclear cells (PBMCs). PBMCs from olive pollen-allergic and non-allergic control subjects were stimulated with olive-pollen extract and Ole e 1 dodecapeptides containing relevant T-cell epitopes. Levels of cytokines were measured in cellular supernatants and gene expression was determined by microarrays, on the RNAs extracted from PBMCs. One hundred eighty-nine differential genes (fold change >2 or <-2, P<0.05) were validated by qRT-PCR in a large population. It was not possible to define a pattern of response according the overall cytokine results but interesting differences were observed, mainly in the regulatory cytokines. Principal component (PCA) gene-expression analysis defined clusters that correlated with the experimental conditions in the group of allergic subjects. Gene expression and functional analyses revealed differential genes and pathways among the experimental conditions. A set of 51 genes (many essential to T-cell tolerance and homeostasis) correlated with the response to aa10-31 of Ole e 1. In conclusion, two peptides derived from Ole e 1 could regulate the immune response in allergic patients, by gene-expression modification of several regulation-related genes. These results open new research ways to the regulation of allergy by Oleaceae family members.

Association of immunological cell profiles with specific clinical phenotypes of scleroderma disease.

This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4(+) and CD8(+) T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies.

Polymorphisms of tumor necrosis factor-α, transforming growth factor-ß, and interleukin-10 in asthma associated with olive pollen sensitization.

Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been correlated with a clinical pattern of asthma. This study analyzes the association between several polymorphims of TNFA (G-308A, C-857T, and C-1031T), IL10 (C-571A and A-1117G), and TGFB (C-509-T) and these sensitizations. These polymorphisms were genotyped by allelic discrimination, in olive pollen-allergic patients (phenotyped for specific Ole e 2 and 10 sensitizations) and healthy controls. Levels of serum-soluble cytokines were correlated with specific genotypes and clinical phenotypes. The results showed that heterozygous TGFB C-509T genotype, besides having the lowest sera TGF- levels, was significantly increased in olive pollen-allergic patients compared with controls. According specific sensitizations, CC genotype of IL10 C-571A could be a protective factor for Ole e 2 sensitization and mainly for asthmatic Ole e 2 sensitized patients compared with asthmatic non-Ole e 2 sensitized patients (OR: 0.26, P = 0.008). In contrast, heterozygous CA genotype was increased in Ole e 2 asthmatic subjects compared to asthmatic non-Ole e 2 sensitized patients. Lastly, heterozygous TNFA G-308A genotype was associated with Ole e 10 sensitization (OR: 2.5, P = 0.04). In conclusion, these results suggest a role of TGF-ß1 in olive-pollen sensitization and TNF-α and IL-10 genotypes in the asthma induced by specific olive-pollen allergens.

Visual hallucinations and HLA class II antigens in cortical dementia.

BACKGROUND: Visual hallucinations are a core feature of dementia with Lewy bodies (DLB) and have been proposed as being part of a narcolepsy-like REM sleep disorder. Selective loss of hypothalamic hypocretin-producing neurons is common to both narcolepsy and the spectrum of Lewy body diseases. We hypothesized that the genetic marker associated with narcolepsy, the HLA class II DR2-DQ6 haplotype, could confer some degree of susceptibility to brainstem-hypothalamic damage leading to the manifestation of visual hallucinations. METHODS: We examined HLA class II haplotypes in 30 patients with prominent visual hallucinations in the context of clinical criteria for DLB and in 30 patients affected by a cortical-type dementia without hallucinations. RESULTS: No significant differences were found in the distribution of DR and DQ antigens. CONCLUSIONS: We conclude that hypothalamic vulnerability in different diseases is not mediated by a common HLA haplotype.