bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature
Authors: Rabin R L , Levinson A I 
Published: October 2008

SummaryThere has been considerable interest in defining the relationship between the expression of allergic and autoimmune diseases in populations of patients. Are patients with autoimmune disease ‘protected’ from developing allergic (immunoglobulin E-mediated) diseases? Does the establishment of an atopic phenotype reduce the risk of the subsequent development of autoimmune diseases? Although there are clinical studies addressing this question, methodological problems, particularly in identification of atopic subjects, limits their usefulness. Moreover, an immune-based explanation of the observed epidemiological findings has relied on a paradigm that is currently undergoing increased scrutiny and modification to include newly defined effector cell subsets and the interaction between genetic and environmental factors, such as early endotoxin or mycobacterial exposure. To address this question, we reviewed a series of clinical reports that addressed coincidence or co-prevalence of atopy with four autoimmune diseases: psoriasis, rheumatoid arthritis, multiple sclerosis and type I diabetes mellitus. We present a model whereby active T helper type 1 (Th1) inflammation may suppress the development of atopy, and atopy may suppress the severity but not necessarily the onset of autoimmunity, and then discuss our model in the context of mechanisms of adaptive immunity with particular reference to the Th1/Th2 paradigms. Because the ultimate goal is to ameliorate or cure these diseases, our discussion may help to predict or interpret unexpected consequences of novel therapeutic agents used to target autoimmune or atopic diseases.
Genetic imprinting of autoantibody repertoires in systemic lupus erythematosus patients
Authors: Silverman G J , Srikrishnan R , Germar K , Goodyear C S , Andrews K A , Ginzler E M , Tsao B P 
Published: October 2008

SummarySystemic lupus erythematosus (SLE) is an autoimmune disease distinguished by great heterogeneity in clinical manifestations and autoantibody expression. While only a handful of autoantibody specificities have proved useful for clinical diagnosis, to characterize complex lupus-associated autoantibody profiles more fully we have applied proteome microarray technology. Our multiplex microarrays included control ligands and 65-autoantigens, which represent diverse nuclear and cytoplasmic antigens recognized by disease-associated and natural autoantibodies. From longitudinal surveys of unrelated SLE patients, we found that autoantibody profile patterns can be patient-specific and highly stable overtime. From profiles of 38 SLE patients that included 14 sets of SLE twins, autoantibodies to the phospholipid neo-determinants, malondialdehyde (MDA) and phosphorylcholine (PC), which are exposed on apoptotic but not healthy cells, were among the most prevalent and highly expressed. We also found that immunoglobulin M (IgM) reactivity to MDA and PC ligands had significant direct correlations with DNA-containing antigens, while such a general relationship was not found with a panel of RNA-related antigens, or for IgG-autoantibodies. Significantly, hierarchical analysis revealed co-distribution/clustering of the IgM autoantibody repertoire patterns for six of 14 twin sets, and such patterns were even more common (10 of 14) for IgG autoantibody profiles. Our findings highlight the potentially distinct roles of IgM and IgG autoantibodies, as we postulate that the direct correlations for IgM autoantibodies to DNA antigens with apoptosis-related determinants may be due to co-expression arising from common pro-homeostatic protective roles. In contrast, the sharing of IgG autoantibody fingerprints by monozygotic twins suggests that lupus IgG autoantibodies can arise in predisposed individuals in genetically determined patterns.
Mutations in CHD7 in patients with CHARGE syndrome cause T–B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome
Authors: Gennery A R , Slatter M A , Rice J , Hoefsloot L H , Barge D , McLean-Tooke A , Montgomery T , Goodship J A , Burt A D , Flood T J , Abinun M , Cant A J , Johnson D 
Published: October 2008

Summary
More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are associated with T–B + NK + SCID phenotype. Severe immunodeficiency with CHARGE syndrome has been noted only rarely Omenn syndrome is a rare autosomal recessive form of SCID with erythroderma, hepatosplenomegaly, lymphadenopathy and alopecia. Hypomorphic recombination activating genes 1 and 2 mutations were first described in patients with Omenn syndrome. More recently, defects in Artemis, RMRP, IL7Rα and common gamma chain genes have been described. We describe four patients with mutations in CHD7, who had clinical features of CHARGE syndrome and who had T–B + NK + SCID (two patients) or clinical features consistent with Omenn syndrome (two patients). Immunodeficiency in patients with DiGeorge syndrome is well recognized − CHARGE syndrome should now be added to the causes of T–B + NK + SCID, and mutations in the CHD7 gene may be associated with Omenn-like syndrome.
Associations of MICB with cervical cancer in north-eastern Thais: identification of major histocompatibility complex class I chain-related gene B motifs influencing natural killer cell activation
Authors: Jumnainsong A , Jearanaikoon P , Khahmahpahte S , Wongsena W , Romphruk A V , Chumworathayi B , Vaeteewoottacharn K , Ponglikitmongkol M , Romphruk A , Leelayuwat C 
Published: October 2008

Summary
The expression of MICB, a member of the major histocompatibility complex class I chain-related gene B family, is induced in response to cellular stress. It is one of the ligands to the NKG2D receptor. MICB is polymorphic, but the distribution of MICB polymorphism in north-eastern Thais and their potential associations with cancer have not yet been elucidated. In this study, polymerase chain reaction–sequence-specific primers were developed to identify 15 MICB alleles and one group of alleles. We performed MICB typing in 100 healthy north-eastern Thai females (NETF) and 99 cervical cancer patients to evaluate the association of MICB polymorphisms and the risk of developing cervical cancer. Eight and nine alleles were detected in the NETF and cervical cancer respectively. MICB*00502 was associated negatively with a corrected P-value of 0·0009, suggesting the existence of a protective allele in cervical cancer. Amino acid substitutions carried by this allele were investigated for their potential involvement in natural killer (NK) cell activation. Although lysine at amino acid position 80 (Lys80) and aspartic acid at position 136 (Asp136) were associated negatively with cervical cancer, only MICB carrying Asp136 could induce NK cell killing more efficiently than MICB-Lys80 when the NK cells were blocked by anti-NKG2D. This result suggested that aspartic acid at position 136 may affect NKG2D binding, leading to different degrees of immune cell activation.
Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice
Authors: Choi J-J , Yoo S-A , Park S-J , Kang Y-J , Kim W-U , Oh I-H , Cho C-S 
Published: October 2008

SummaryMesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.
Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene
Authors: Staples E R , McDermott E M , Reiman A , Byrd P J , Ritchie S , Taylor A M R , Davies E G 
Published: October 2008

Summary
Immunodeficiency affects over half of all patients with ataxia telangiectasia (A-T) and when present can contribute significantly to morbidity and mortality. A retrospective review of clinical history, immunological findings, ataxia telangiectasia mutated (ATM) enzyme activity and ATM mutation type was conducted on 80 consecutive patients attending the National Clinic for Ataxia Telangiectasia, Nottingham, UK between 1994 and 2006. The aim was to characterize the immunodeficiency in A-T and determine its relationship to the ATM mutations present. Sixty-one patients had mutations resulting in complete loss of ATM kinase activity (group A) and 19 patients had leaky splice or missense mutations resulting in residual kinase activity (group B). There was a significantly higher proportion of patients with recurrent sinopulmonary infections in group A compared with group B (31 of 61 versus four of 19 P = 0·03) and a greater need for prophylactic antibiotics (30 of 61 versus one of 19 P = 0·001). Comparing group A with group B patients, 25 of 46 had undetectable/low immunoglobulin A (IgA) levels compared with none of 19; T cell lymphopenia was found in 28 of 56 compared with one of 18 and B cell lymphopenia in 35 of 55 compared with four of 18 patients (P = 0·00004, 0·001 and 0·003 respectively). Low IgG2 subclass levels and low levels of antibodies to pneumococcal polysaccharide were more common in group A than group B (16 of 27 versus one of 11 P = 0·01; 34/43 versus six of 17 P = 0·002) patients. Ig replacement therapy was required in 10 (12·5%) of the whole cohort, all in group A. In conclusion, A-T patients with no ATM kinase activity had a markedly more severe immunological phenotype than those expressing low levels of ATM activity.
Leishmania surface protein gp63 binds directly to human natural killer cells and inhibits proliferation
Authors: Lieke T , Nylén S , Eidsmo L , McMaster W R , Mohammadi A M , Khamesipour A , Berg L , Akuffo H 
Published: October 2008

SummaryNatural killer (NK) cells contribute to immunity as the first line of defence in numerous infections by early cytokine secretion and cytotoxicity. In Leishmania infection, NK cells contribute with interferon-γ and may assist in directing the immune response towards T helper type 1, which is essential for successful control of the parasites. Thus, NK cells may play an important role in both resistance and control of the infection. However, during Leishmania infection NK cells show signs of suppression. To explore the reason for this suppression, we exposed naive and interleukin (IL)-2 activated NK cells directly to promastigotes of Leishmania major in vitro. As a rapid consequence of contact between naive NK cells and promastigotes, expression of NK cell receptors show significant changes. We identify one of the major surface molecules of promastigotes, glycoprotein (gp) 63, as an important agent for these suppressive effects by using promastigotes of a gp63ko strain of L. major. Furthermore, proliferation of IL-2-activated purified NK cells is suppressed after exposure to the wild-type but not to gp63ko promastigotes. However, gp63ko L. major induced no NK cell proliferation when NK cells were co-cultured with peripheral blood mononuclear cells populations such as CD14+ monocytes or T cells.
Induction of IL-10 producing CD4+ T cells with regulatory activities by stimulation with IL-10 gene-modified bone marrow derived dendritic cells
Authors: Fu C-L , Chuang Y-H , Huang H-Y , Chiang B-L 
Published: October 2008

SummaryDendritic cells (DCs) can induce both tolergenic as well as effective immune responses in the lung. Pulmonary DCs producing interleukin (IL)-10 mediated tolerance induced by respiratory exposure to antigen. IL-10 is an important immunosuppressive cytokine, which inhibits maturation and function of DC. To assess whether IL-10 producing DCs can exert the tolergenic effect through the differentiation of regulatory T cells, bone marrow derived DCs were genetically modified by IL-10 expressing adenovirus. IL-10 gene modified DCs (Ad-IL-10-DC) displayed a characteristic phenotype of immature DCs. Here we showed that in vitro repetitive stimulation of naïve DO11·10 CD4+ T cells with Ad-IL-10-DCs resulted in a development of IL-10 producing T-cell regulatory cells. These T cells could not proliferate well but also lost their ability to produce interferon-γ upon restimulation with irradiated splenocytes and ovalbumin peptide. Furthermore, in co-culture experiments these T cells inhibited the antigen-driven proliferation of naïve CD4+ T cells in a dose-dependent manner. Our findings demonstrated that IL-10 producing DCs had the potential to induce the differentiation of Tr1-like cells and suggested their therapeutic use.
Essential role of toxin A in C. difficile 027 and reference strain supernatant-mediated disruption of Caco-2 intestinal epithelial barrier function
Authors: Sutton P A , Li S , Webb J , Solomon K , Brazier J , Mahida Y R 
Published: October 2008

Summary
Clostridium difficile induces mucosal inflammation via secreted toxins A and B and initial interactions between the toxins and intestinal epithelial cells (which lead to loss of barrier function) are believed to be important in disease pathogenesis. Secreted toxin-specific antibodies may inhibit such interactions. Using the Caco-2 epithelial cell line, we have investigated the use of an anti-toxin A monoclonal antibody (ATAA) in providing protection against toxin A-mediated disruption of epithelial barrier function (assessed by measurement of transepithelial electrical resistance and luminal to basolateral flux of labelled dextran). In contrast to free antibody, ATAA conjugated to sepharose beads was more effective in neutralizing the activity of purified toxin A. Sepharose bead-conjugated ATAA was subsequently used to investigate the contribution of toxin A in epithelial injury mediated by C. difficile supernatant samples (containing toxins A, B and other products). Loss of barrier function mediated by apical application of supernatant samples of reference and epidemic 027 strains of C. difficile was abrogated by neutralization of toxin A. However, this was not the case when the supernatant samples were applied to the basal surface of epithelial monolayers. In conclusion, our studies have shown that (i) sepharose bead-conjugated ATAA is more effective in neutralizing toxin A than free antibody and (ii) when the apical (luminal) surface of epithelial monolayers is exposed to the secretory products of reference and 027 strains of C. difficile, toxin A is required for the initial injury that leads to loss of barrier function.
Protein biochip array technology for cytokine profiling predicts etanercept responsiveness in rheumatoid arthritis
Authors: Fabre S , Dupuy A M , Dossat N , Guisset C , Cohen J D , Cristol J P , Daures J P , Jorgensen C 
Published: October 2008

SummaryIn rheumatoid arthritis (RA) there are currently no useful indicators to predict a clinical response to tumour necrosis factor-α (TNF-α) blockade. The purpose of this study was to determine the role of peripheral blood cytokine profiling in differentiating between a good versus poor response to etanercept in RA. Peripheral blood samples were collected at baseline and at 3 months from 33 patients with active disease who were treated twice weekly by etanercept therapy. Responders are defined by the presence of three of four American College of Rheumatology criteria: ≥20% decrease in C-reactive protein (CRP), visual analogue score of disease activity, erythrocyte sedimentation rate and improvement of the disease activity score (28; four values) by ≥1·2 obtained at 3 months. Twelve cytokines were measured from serum collected on days 0 and 90 by proteomic array (protein biochip array, Investigator Evidence, Randox France), including interleukin (IL)-6, TNF-α, IL-1a, IL-1b, IL-2, IL-8, interferon-γ, IL-4, IL-10, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF) and vascular endothelium growth factor. Our results showed that high serum levels of MCP-1 and EGF were associated with a response to etanercept. In addition, the increase of two combined parameters CRP and EGF was predictive of a response to etanercept treatment at 3 months (sensitivity: 87·5% and specificity: 75%, accuracy: 84·4%). These findings suggest that cytokine profiling by proteomic analysis before treatment initiation may help to identify a responder patient to TNF-α blocking agents in RA.
An approach to the patient with urticaria
Authors: Deacock S J 
Published: October 2008

SummaryPatients with urticaria make up a large proportion of the referrals to allergy clinics. There are many causes of urticaria and it is the clinical history which is most important when attempting to identify potential causes; however, urticaria is very often idiopathic. In a small minority of patients urticaria may be a symptom of a serious underlying medical illness or the allergic symptoms may progress to cause systemic reactions, and it is important to identify these patients and to remember that severe urticaria is a distressing and disabling condition. This review will discuss classification, investigation and treatment of urticaria and will consider some of the more unusual types of urticaria that may be encountered in the out-patient clinic.
Clinical Immunology Review Series: An approach to the patient with anaphylaxis
Authors: El-Shanawany T , Williams P E , Jolles S 
Published: October 2008

Summary
Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction. While there is agreement as to this definition of anaphylaxis, the clinical presentation is often variable and it is not uncommon for there to be debate after the event as to whether anaphylaxis had actually occurred. The management of anaphylaxis falls into two distinct phases: (1) emergency treatment and resuscitation of a patient with acute anaphylaxis and (2) the search for a cause for the event and the formulation of a plan to prevent and treat possible further episodes of anaphylaxis. Both aspects are important in preventing death from anaphylaxis and are covered in this review.
Clinical Immunology Review Series: An approach to the use of the immunology laboratory in the diagnosis of clinical allergy
Authors: Williams P , Sewell W A C , Bunn C , Pumphrey R , Read G , Jolles S 
Published: October 2008

SummaryIn the last 10 years UK immunology laboratories have seen a dramatic increase in the number and range of allergy tests performed. The reasons for this have been an increase in the incidence of immunoglobulin E (IgE)-mediated allergic disease set against a background of greater public awareness and more referrals for assessment. Laboratory testing forms an integral part of a comprehensive allergy service and physicians treating patients with allergic disease need to have an up-to-date knowledge of the range of tests available, their performance parameters and interpretation as well as the accreditation status of the laboratory to which tests are being sent. The aim of this review is to describe the role of the immunology laboratory in the assessment of patients with IgE-mediated allergic disease and provide an up-to-date summary of the tests currently available, their sensitivity, specificity, interpretation and areas of future development.
Dehydroepiandrosterone and metformin regulate proliferation of murine T lymphocytes
Authors: Solano M E , Sander V , Wald M R , Motta A B 
Published: October 2008

Summary
The aim of the present study was to assess the effect of dehydroepiandrosterone (DHEA: 10 µM) and metformin (10 µM and 100 µM) in regulating proliferation of cultured T lymphocytes. T cells were isolated from lymph nodes of prepuberal BALB/c mice. We found that DHEA, metformin and DHEA + metformin added to the incubation media diminished proliferation of T cells. The inhibition by DHEA was higher than that produced by metformin, while the combined treatment showed a synergistic action that allowed us to speculate distinct regulatory pathways. This was supported later by other findings in which the addition of DHEA to the incubation media did not modify T lymphocyte viability, while treatment with metformin and DHEA + metformin diminished cellular viability and increased both early and late apoptosis. Moreover, DHEA diminished the content of the anti-oxidant molecule glutathione (GSH), whereas M and DHEA + metformin increased GSH levels and diminished lipid peroxidation. We conclude that DHEA and metformin diminish proliferation of T cells through different pathways and that not only the increase, but also the decrease of oxidative stress inhibited proliferation of T cells, i.e. a minimal status of oxidative stress, is necessary to trigger cellular response.
Renal damage and death in weaned mice after oral infection with Shiga toxin 2-producing Escherichia coli strains
Authors: Brando R J F , Miliwebsky E , Bentancor L , Deza N , Baschkier A , Ramos M V , Fernández G C , Meiss R , Rivas M , Palermo M S 
Published: October 2008

Summary
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infections are considered a public health problem in both developed and developing countries because of their increasing incidence and the severity of clinical presentation. Approximately 10% of infected patients develop complications such as haemolytic uraemic syndrome (HUS) characterized by acute renal failure, thrombocytopenia and haemolytic anaemia. The precise sequence of events leading to HUS is still understood incompletely. Because of the lack of a reproducible small animal model for EHEC infections, in vivo studies examining EHEC–host early interactions are limited and insufficient. The aim of this study was to characterize the weaned BALB/c mouse as a model of E. coli O157:H7 infection. In this paper we report that human Shiga toxin 2 (Stx2)-producing EHEC strains can adhere to the intestinal epithelium of weaned BALB/c mice, and produce local damage which leads to systemic disease and death in a percentage of infected mice. The lethality of the EHEC strain is closely age-dependent, and is related to the bacterial ability to colonize intestine and to produce Stx2. It can be concluded that the weaned BALB/c mouse can be used as a small animal model to study host early responses, and the role of bacterial pathogenic factors in the induction of systemic disease, thus providing a useful tool for the evaluation of therapeutic or vaccine approaches.