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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 95 (1976), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW-g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross-react with HMW-g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten-free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the DH patients. This diet-associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW-g and elastin in healthy controls and CD patients, while no such correlation was found in patients with DH. These findings could indicate that HMW-g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that DH may be an autoimmune disease due to cross-reactivity between dietary glutenin and dermal elastin.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Scandinavian journal of immunology 60 (2004), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mannan-binding lectin (MBL) is a pattern recognition receptor in the innate immune system. It recognizes certain sugar residues arranged in a pattern that enables MBL to bind with sufficient strength. Such sugar patterns are common on the surface of many microorganisms, and MBL has therefore been considered to be an agent that can discriminate between self and nonself. There is, however, increasing evidence supporting that MBL, like many membrane-bound C-type lectin-like receptors, also helps to dispose of various outworn or abnormal body components. Most self-components are protected with sialic acid or galactose that disrupt the pattern of the sugars that MBL can bind, but MBL may be significantly involved in the elimination of self-components that have lost these protective terminal residues. The role of MBL in the clearance of invading pathogens has previously been thoroughly reviewed. Here, we review some findings that support the notion that MBL may contribute to noninflammatory removal of immune complexes and abnormal cells by the reticuloendothelial system. Defects in this clearance mechanism may cause an accumulation of potentially dangerous self-components, thereby increasing the likelihood of chronic inflammation and autoimmunity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The interaction with adhesion molecules expressed by vascular endothelium is the first step in lymphocyte infiltration into tissues. At both cutaneous and mucosal sites interleukin-10 (IL-10), IL-12 and transforming growth factor (TGF)-β are important regulators of chronic inflammatory disease, where cutaneous lymphocyte-associated antigen (CLA) and αE integrin (CD103) may be expressed. Unlike CLA, CD103 is not believed to play a role in tissue-specific homing but may help to retain T cells within epithelial layers. We have previously shown that IL-12 alone can together with an unknown cofactor increase the expression of CLA. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8+ but not CD4+ T cells. While IL-12 increased superantigen-stimulated expression of CLA, this cytokine strongly inhibited the CD103 expression, and a combination of IL-12 and TGF-β completely abrogated the induced CD103 expression. Conversely, IL-10 suppressed CLA but increased CD103 expression.These findings indicate that, in addition to suppressing the development of Th1-mediated inflammatory responses, IL-10 may also inhibit the migration of CD8+ T cells into the skin while IL-12 promotes such migration. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL-10 and IL-12, and the balance between these cytokines could influence the T-cell migration of inflammatory cells into epithelial tissues.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 6 (1977), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Using new objective methods for measuring, independently, phagocytosis and killing, it was demonstrated that Candida albicans opsonized by C3-deficient serum was ingested but not killed in vitro by human polymorphonuclear leukocytes. Killing could be induced by adding purified C3 to the C3-deficient serum. It is concluded that C3 participates directly in the intracellular process leading to phagocytic killing of C. albicans.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Respiratory tract infections, allergies and otitis media are common problems in early childhood. Our aim was to evaluate in a longitudinal community-based cohort study the association between maturation of immunoglobulin (Ig) and mannan-binding lectin (MBL) responses and disease manifestations in the first 4 years of life. Sustained low levels of IgA proved the strongest single indicator of susceptibility for recurrent otitis media (P = 0.008) and respiratory tract infections (P = 0.02), and this condition was also associated with low production of IgG subclasses. About 7% of the cohort had sustained low levels of MBL (〈0.4 mg/l). Low MBL did not predispose to any ailments studied, but children with low IgA and recurrent otitis media had relatively low MBL at birth, which failed to increase during the study period and was significantly reduced at the age of 4 years (P = 0.04). MBL levels increased from birth to 2 years (P 〈 0.0001) and were higher in children than in adults (P = 0.001). The increase was 1.9-fold in children with no recorded clinical events and 1.7-fold in children with asthma or infections, but significantly lower, 1.2-fold, in children with recurrent otitis media. Low levels of IgA within the normal range may reveal disease susceptibility not detected by conventional criteria. Slow maturation of Ig appears to be the main factor of susceptibility during childhood, but a strong corollary role for MBL is indicated by the high levels produced during childhood as well as the precipitation of disease in children with low levels of MBL and Ig.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mannose-binding lectin (MBL) is an important component of innate immunity that can bind to certain sugar residues on the surface of many types of pathogenic micro-organisms. On binding, MBL generates opsonic activity mainly through activation of the complement system. Genetically determined MBL deficiency is very common and can be associated with increased susceptibility to a variety of infections, especially in children and immunosuppressed individuals. The potential benefits of MBL reconstitution therapy therefore need to be evaluated. We have carried out a phase I safety and pharmacokinetic study on 20 MBL-deficient healthy adult volunteers. The MBL was prepared from plasma of nonremunerated, voluntary Danish donors tested and found negative for hepatitis B surface antigen, antibodies to human immunodeficiency virus (HIV) and hepatitis C virus. Each volunteer received a total of 18 mg of MBL in three 6 mg doses given intravenously, once weekly over a period of 3 weeks. The volunteers were closely monitored at the University Hospital in Reykjavik for 8 h after each infusion and daily thereafter for 5 days after each infusion. No adverse clinical or laboratory changes were observed in any of the 20 participants, and frequent measurements did not reveal any signs of infusion-associated complement activation. No antibodies to MBL, HIV or hepatitis viruses were observed 24 weeks after the last infusion. Serum MBL levels increased up to normal levels (1200–4500 ng/ml) immediately after each infusion, but the half-life of the infused MBL was highly variable, ranging from 18 to 115 h (mean 69.6). It is concluded that infusion of purified MBL as prepared by Statens Serum Institut (SSI) is safe. However, adults have to be given at least 6 mg twice or thrice weekly for maintaining protective MBL levels assumed to be about 1000 ng/ml.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Psoriasis is a T-cell mediated inflammatory skin disease which has been associated with group A, β-haemolytic streptococcal infections. Four 20 a.a. long M6-peptides sharing 5–6 a.a. sequences with human epidermal keratins were identified. To investigate the role of potentially cross-reactive T cells in the pathogenesis of psoriasis, interferon-γ (IFN-γ) and interleukin-4 (IL-4) responses of circulating T cells to these peptides were analysed by ELISPOT and RT-PCR in 14 psoriatic patients, 12 healthy individuals and six patients with atopic dermatitis (AD). Untreated psoriatic patients’ responses were significantly higher to these peptides than healthy and AD controls, while responses to a control M6-peptide, not sharing sequences with keratin, were negligible in all groups. No difference was found in response to streptokinase/streptodornase (SK/SD). M6-protein and peptides exclusively elicited IFN-γ production, with little IL-4 production, even in AD patients. Interferon-γ responses to all the M6-peptides were abolished after successful treatment of psoriatic patients, but responses to SK/SD were unaffected. The results indicate that active psoriasis is associated with Th1-like cells responding to streptococcal M6-peptides sharing sequences with human epidermal keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein specific Th1-like cells that cross-react with human epidermal keratin.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The association of psoriasis with throat infections by streptococcus pyogenes suggests a potential antigenic target for the T cells that are known to infiltrate dermis and epidermis of psoriatic skin. Streptococcal M protein shares an extensive sequence homology with human epidermal keratins. Keratins 16 (K16) and 17 (K17) are mostly absent from uninvolved skin but are upregulated in psoriatic lesions. There is increasing evidence that CD8+ T cells play an important effector role in psoriasis and M protein-primed T cells may recognize these shared epitopes in skin via molecular mimicry. To identify candidate epitopes, peptides with sequences from K17 were selected on the basis of predicted binding to HLA-Cw6 and sequence similarities with M6 protein. Matched peptides from the sequence of M6 protein and a set of peptides with poor predicted binding were also selected. Cw6+ individuals with psoriasis and Cw6+ healthy controls, having a family history of psoriasis, were recruited. PBMCs were incubated with the peptide antigens. T-cell activation in the CD4+, CD8+ and later the skin-homing cutaneous lymphocyte-associated antigen (CLA)-expressing subset of CD8+ T cells was evaluated by CD69 expression and intracellular IFN-γ accumulation using flow cytometry. We demonstrate that Cw6+ psoriasis patients had significant CD8+ T-cell IFN-γ responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA+) subset of CD8+ T cells. CD4+ T cells showed only borderline responses. CD8+ T cells from Cw6 + nonpsoriatic individuals responded to some M6 peptides but very rarely to K17 peptides, and this also applied to the CLA+CD8+ subset. These findings indicate that psoriatic individuals have CD8+ T cells that recognize keratin self-antigens and that epitopes shared by streptococcal M protein and human keratin may be targets for the CD8+ T cells that infiltrate psoriatic skin lesions.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Pediatric allergy and immunology 5 (1994), S. 0 
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The predictive value of cord blood IgE (clgE) for atopy and related disorders was investigated. Samples were collected from 792 infants delivered consecutively at the National University Hospital in Reykjavik in 1987. The concentration of IgE, but not that of IgA, was found to increase with increasing gestational age at birth. There was no correlation between IgE and IgA levels in individual samples. At the age of 18–23 months 180 of these children were studied for manifestations of allergy and related disorders. Included were all available infants with detectable (≥ 23 kU/L) clgE. However, infants born by Cesarean section or with IgA exceeding 10 mg/L were excluded because of potential contamination with maternal blood. The clinical evaluation was made without knowledge of the IgE levels. Sixty-six of the 180 participants (36.6%) were judged to have had definite allergic manifestations. However, no striking correlation was found between allergic symptoms and cIgE levels in this study, nor did high levels of IgE add significantly to the predictive value of family history. Children with atopic features had more frequently been affected by otitis media. Unexpectedly, infants with intermediate cIgE levels (0.2–0.6 kU/L) were significantly less affected by otitis media than children with unmeasurable (〈 0.2 kU/L) or high (≥ 0.7 kU/L) cIgE levels. It is concluded that cord blood IgE can not be used to predict allergic manifestations in children under the age of 2 years.
    Type of Medium: Electronic Resource
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