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1.
Brain Behav Immun ; 38: 91-9, 2014 May.
Article in English | MEDLINE | ID: mdl-24389156

ABSTRACT

Circulating 45 and 62kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N=355), their unaffected siblings (N=142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62kDa antibodies are correlated with autism severity: the 45kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62kDa autoAb in the child is significantly associated with presence of the 39 and/or 73kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering.


Subject(s)
Autoantibodies/blood , Brain/immunology , Child Development Disorders, Pervasive/immunology , Adolescent , Adult , Autoantibodies/immunology , Autoimmunity , Child , Child, Preschool , Female , Humans , Italy , Male , Middle Aged , Young Adult
2.
J Perinatol ; 33(9): 691-7, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23599119

ABSTRACT

OBJECTIVE: To investigate the impact of probiotic Bifidobacterium longum ssp. infantis on the fecal microbiota and plasma cytokines in neonates with congenital heart disease. STUDY DESIGN: Sixteen infants with congenital heart disease were randomly assigned to receive either B. infantis (4.2 × 10(9) colony-forming units two times daily) or placebo for 8 weeks. Stool specimens from enrolled infants and from six term infants without heart disease were analyzed for microbial composition. Plasma cytokines were analyzed weekly in the infants with heart disease. RESULTS: Healthy control infants had increased total bacteria, total Bacteroidetes and total bifidobacteria compared to the infants with heart disease, but there were no significant differences between the placebo and probiotic groups. Plasma interleukin (IL)10, interferon (IFN)γ and IL1ß levels were transiently higher in the probiotic group. CONCLUSION: Congenital heart disease in infants is associated with dysbiosis. Probiotic B. infantis did not significantly alter the fecal microbiota. Alterations in plasma cytokines were found to be inconsistent.


Subject(s)
Bifidobacterium , Cytokines/blood , Feces/microbiology , Heart Defects, Congenital/blood , Heart Defects, Congenital/microbiology , Probiotics/therapeutic use , Cohort Studies , Female , Heart Defects, Congenital/therapy , Humans , Infant, Newborn , Male , Pilot Projects
3.
Acta Derm Venereol ; 79(2): 98-104, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10228625

ABSTRACT

Mast cells contain large amounts of the powerful serine proteinases, tryptase and chymase, of which only chymase can be inactivated by serum protease inhibitors. In this study, 20 patients with psoriasis and a control group of 13 with atopic dermatitis were biopsied for lesional and non-lesional skin specimens. The presence of chymase inhibitor alpha 1-proteinase inhibitor (alpha 1-PI), alpha 1-antichymotrypsin (alpha 1-AC), alpha 2-macroglobulin (alpha 2-MG) and C1-esterase inhibitor (C1-Inh) immunoreactivity in mast cells was verified using the sequential double-staining method. Tryptase- and chymase-positive mast cells were stained enzyme-histochemically. Tryptase-positive mast cells were increased in number in the upper dermis of the psoriatic lesion compared with lesion-free psoriatic skin (308 +/- 109 vs. 100 +/- 29 cells/mm2, respectively, mean +/- SD, p < 0.0005, t-test) while the percentage of mast cells showing chymase activity was decreased (76.8 +/- 22.1% vs. 28.6 +/- 14.4%, p < 0.0005). These findings are consistent with our previous ones. In contrast to the decreased percentage of chymase-positive mast cells, a novel finding was that the percentages of alpha 1-AC+ (86.9 +/- 7.2% vs. 59.5 +/- 12.6%, p < 0.0005), alpha 1-PI+ (72.2 +/- 14.9% vs. 33.4 +/- 18.6%, p < 0.0005) and alpha 2-MG+ (16.8 +/- 7.0% vs. 6.2 +/- 3.5%, p < 0.002) mast cells were significantly higher in the psoriatic lesion with the exception of the percentage of C1-Inh+ mast cells (13.7 +/- 10.0% vs. 11.0 +/- 6.1%, p < 0.7). The localization of these inhibitors in mast cells is not a characteristic feature of psoriasis, since mast cells in atopic dermatitis skin also showed immunoreactivity though in slightly lower percentages. Previously, we have shown that MCTC (tryptase+, chymase+) mast cells increase in number in the psoriatic lesion but chymase becomes inactive. The results of this study show again the decreased chymase activity, which could be due to increased levels of its inhibitors (alpha 1-AC, alpha 1-PI and alpha 2-MG) in the same mast cells. Thus, active tryptase could promote inflammation but chymase seems not to be an important mediator in the pathomechanism of psoriasis.


Subject(s)
Dermatitis, Atopic/enzymology , Mast Cells/enzymology , Protease Inhibitors/metabolism , Psoriasis/enzymology , Serine Endopeptidases/metabolism , Adult , Aged , Case-Control Studies , Chymases , Dermatitis, Atopic/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Psoriasis/pathology , Tryptases
4.
J Allergy Clin Immunol ; 99(4): 502-7, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9111495

ABSTRACT

BACKGROUND: No information is available on allergenicity of tree nut oils, and information on peanut oils has been conflicting. Many of the nut oils now on the market undergo minimal processing and may contain residual antigen. OBJECTIVE: This study was carried out to determine whether several of the new "gourmet" tree nut oils, as well as peanut oils, contain residual proteins that could bind IgE from sera of patients with allergy. METHODS: Several brands of walnut, almond, hazelnut, pistachio, and macadamia nut oils were examined. Peanut oils, both unrefined oils (which have been shown to contain allergenic proteins) and refined oils (without previously demonstrable allergens), were also examined to confirm reproducibility of immunoreactivity as reported by other investigators. Oils were extracted with 0.2 mol/L ammonium bicarbonate, and protein concentrations in the aqueous extracts were measured. IgE binding was assayed by slot-blot and Western immunoblotting. Pooled sera from patients with a history of systemic reactions to various tree nuts or peanuts were used as appropriate. RESULTS: The oil extracts known to be from oils that had undergone less processing at lower temperatures tended to demonstrate qualitatively greater IgE binding and higher protein concentrations. CONCLUSIONS: Tree nut and peanut oils may pose a threat to patients with allergy, depending on the method of manufacture and processing.


Subject(s)
Allergens/immunology , Food Handling/methods , Nuts/immunology , Plant Oils , Allergens/analysis , Arachis/immunology , Humans , Immunoblotting/methods , Immunoglobulin E/blood , Peanut Oil , Plant Proteins/analysis , Plant Proteins/immunology , Trees
5.
J Autoimmun ; 4(2): 369-80, 1991 Apr.
Article in English | MEDLINE | ID: mdl-1883483

ABSTRACT

As a prelude to deciphering the mechanisms of intrathymic T-cell maturation we produced a panel of 18 monoclonal antibodies (mAbs) against chicken thymic stromal elements. Eleven of these detected epithelial cells. They were: pan-epithelial; subcapsule and peri-vascular (pan type 1 epithelium); subcapsular, perivascular and medulla; medulla; or cortex. Of particular interest were the sub-specificities within these regions, especially the subcapsular region. Four mAbs stained both epithelial and non-epithelial cells in discrete regions. In addition, three mAbs recognized only non-epithelial cells. One identified macrophages scattered throughout the thymus, another the connective tissue and another the medullary vascular endothelium. These reagents have provided an extensive profile of the thymic stromal architecture and revealed that these cells are equally as complex as the T cells whose differentiation they induce and regulate. While the mAbs provide a valuable means for studying the mechanisms of normal thymopoiesis, their clinical significance is unknown. UCD line 200 chickens develop an autoimmune disease manifest by dermal and internal organ fibrosis, T cell infiltrates of skin and other affected organs and production of multiple autoantibodies. We have used our panel of mAbs to evaluate the thymic microenvironment in these autoimmunity-prone chickens. A comparative analysis with control chickens revealed striking deficiencies in the L200 subcapsular regions coupled with excessive expression of MHC class II antigens, particularly in the cortex. We hypothesize that these abnormalities induce altered T-cell differentiation, thereby predisposing the L200 chickens to autoimmune disease.


Subject(s)
Autoimmune Diseases/pathology , Disease Models, Animal , Scleroderma, Systemic/pathology , Thymus Gland/pathology , Animals , Antibodies, Monoclonal/immunology , Antibody Specificity , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Cell Differentiation , Chickens/genetics , Chickens/immunology , Epithelium/immunology , Epithelium/pathology , Fluorescent Antibody Technique , Scleroderma, Systemic/genetics , Scleroderma, Systemic/immunology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Thymus Gland/immunology , Thymus Hormones/deficiency
6.
Clin Immunol Immunopathol ; 56(2): 169-84, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2143126

ABSTRACT

UCD line 200 chickens develop an inherited fibrotic disease associated with the production of antinuclear antibodies, antibodies to type II collagen, and early skin lesions characterized by intense T lymphocyte infiltrates. In the present study we have investigated the hypothesis that developmental abnormalities in T lymphocyte differentiation predispose the line 200 chickens to autoimmune disease. The status of the thymic microenvironment in these birds during ontogeny was studied with an extensive panel of monoclonal antibodies (mAbs) reactive with distinct stromal cell subsets including MHC determinants. In addition, their T-cell graft-versus-host reactivity and responses to mitogenic stimulation and interleukin (IL)-2 were also analyzed. Line 200 chickens have profound defects in thymic structure with a virtual complete absence of antigens specific for type I epithelium which lines the thymic subcapsular and perivascular regions. There are excessive levels of MHC class II positive cells, particularly in the cortex, and B cells/subset macrophages identified by mAb MUI 36. These defects are found from the late embryonic period, long before clinical disease is manifest. Furthermore, by FACS analysis, line 200 thymocytes have a major increase in IL-2 receptor density. In addition, line 200 chicken peripheral blood lymphocytes (PBL) respond poorly to mitogenic agents and have a reduced response to IL-2. Finally, it is important to note that line 200 PBL produce a normal graft-versus-host reaction. We propose that these abnormalities in T-cell differentiation are selective, not global, and may be reflective of a defect in thymic education resulting in an inappropriate response to self-antigens.


Subject(s)
Poultry Diseases/immunology , Scleroderma, Systemic/veterinary , T-Lymphocytes/cytology , Animals , Antigens, Differentiation, T-Lymphocyte/analysis , CD3 Complex , CD4 Antigens/analysis , CD8 Antigens , Cell Differentiation , Chickens , Flow Cytometry , Fluorescent Antibody Technique , Interleukin-2/pharmacology , Lymphocyte Activation , Mitogens/pharmacology , Receptors, Antigen, T-Cell/analysis , Scleroderma, Systemic/immunology , T-Lymphocytes/immunology , Thymus Gland/cytology
7.
Arthritis Rheum ; 32(8): 1031-40, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2669767

ABSTRACT

University of California, Davis (UCD) line 200 chickens spontaneously develop a progressive fibrotic syndrome with features similar to those observed in human autoimmune connective tissue diseases, including fibrosis, vascular occlusion, and lymphocytic infiltration of the comb, skin, digits, and viscera. Beginning at 2 weeks post hatch, line 200 chickens develop intense lymphocytic infiltration of the comb and dorsal neck skin. To further characterize the nature of these cellular infiltrates, weekly serial skin biopsy specimens from line 200 and control birds were examined using hematoxylin and eosin staining and indirect immunofluorescence with a library of mouse anti-chicken monoclonal antibodies specific for lymphocyte markers. In situ staining performed on serial skin sections revealed the presence of large groups of T cells beginning at 2 weeks of age. Further characterization of these infiltrates demonstrated the presence of both T helper and T cytotoxic/suppressor cells with a mean +/- SD T4:T8 ratio of 1.44 +/- 0.29 by 4 weeks of age. As the lesions progressed, the infiltrates also contained distinct groups of B cells as characterized by MUI 36. In addition, the lesions were strongly positive for B-L (Ia) antigen, which was noted on B cells, monocytes/macrophages, activated T cells, and fibroblasts. The skin sections were negative for 2 different macrophage monoclonal antibodies at all time-points. Upon extraction from affected skin, 42.0 +/- 13.06% (mean +/- SD) of these cells were positive for B-L, 35.10 +/- 6.51% were T cells, and 31.25 +/- 3.14% were recognized by MUI 36. Although positive staining for IgG was not found in these extracted cells, 7% of the isolated cells were positive for surface IgM.


Subject(s)
Scleroderma, Systemic/veterinary , T-Lymphocytes/pathology , Animals , Antibodies, Monoclonal , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Chickens , Fluorescent Antibody Technique , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/pathology , Scleroderma, Systemic/immunology , Scleroderma, Systemic/pathology , Skin/blood supply , Skin/immunology , Skin/pathology , T-Lymphocytes/immunology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/pathology
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