Chronic or recurrent Campylobacter enteritis in primary immunodeficiency: A UK national case-series and review of the literature

Campylobacter infection is an important diagnosis to consider in primary immunodeficiency patients with chronic or recurrent diarrhea, particularly in those with very low diagnostic immunoglobulin levels. Macrolides, aminoglycosides, and/or carbapenems are promising treatment options for this potentially debilitating condition

Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling

Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients

Investigating pulmonary and non-infectious complications in common variable immunodeficiency disorders: a UK national multi-centre study

Background: Common Variable Immunodeficiency Disorders (CVID) encompass a spectrum of immunodeficiency characterised by recurrent infections and diverse non-infectious complications (NICs). This study aimed to describe the clinical features and variation in NICs in CVID with and without interstitial lung disease (ILD) from a large UK national registry population. Methods: Retrospective, cross-sectional data from a UK multicentre database (previously known as UKPIN), categorising patients into those with CVID-ILD and those with NICs related to CVID but without pulmonary involvement (CVID-EP; EP= extra-pulmonary involvement only). Results: 129 patients were included. Chronic lung diseases, especially CVID-ILD, are prominent complications in complex CVID, occurring in 62% of the cohort. Bronchiectasis was common (64% of the cohort) and associated with greater pulmonary function impairment in patients with CVID-ILD compared to those without bronchiectasis. Lymphadenopathy and the absence of gastrointestinal diseases were significant predictors of ILD in complex CVID. Although the presence of liver disease did not differ significantly between the groups, nearly half of the CVID-ILD patients were found to have liver disease. Patients with CVID-ILD were more likely to receive immunosuppressive treatments such as rituximab and mycophenolate mofetil than the CVID-EP group, indicating greater need for treatment and risk of complications. Conclusion: This study highlights the significant burden of CVID-ILD within the CVID population with NICs only. The lungs emerged as the most frequently affected organ, with ILD and bronchiectasis both highly prevalent. These findings emphasise the necessity of a comprehensive and multidisciplinary approach in managing CVID patients, considering their susceptibility to various comorbidities and complications

Chronic hepatitis C - immune disturbances in peripheral blood

Although several studies have pointed to an important Treg cell role in chronic hepatitis C immunopathogenesis, the question which cell types are targeted in particular has not been addressed yet. Based on the hypothesis that Treg cells are related to immunosuppression and the development of chronicity in HCV infection we evaluated the effect Treg cells have on particular lymphocyte subpopulations in HCV infected patients. In particular, there is profound failure to generate high numbers of mature effector CD8+ T cells in chronic HCV, thus we hypothesized that inhibition of proliferation and associated maturation of CD8+ T cells might be most significantly affected. In parallel we attempted to evaluate a possible immune regulatory role of B lymphocytes in chronic hepatitis C patients. […]Σκοπός της παρούσας μελέτης ήταν να μελετήσουμε το ρόλο που διαδραματίζουν τα Treg λεμφοκύτταρα κατά τη χρόνια λοίμωξη από τον ιό της ηπατίτιδας C σε σχέση με τα υγιή άτομα και να αναλύσουμε την επίδραση αυτών των κυττάρων σε διαφορετικούς υποπληθυσμούς λεμφοκυττάρων. Παράλληλος στόχος ήταν η ανάλυση των φαινοτυπικών δεικτών και της ικανότητας έκκρισης αντιικών κυτταροκινών των κεντρικών και εκτελεστικών λεμφοκυττάρων μνήμης του περιφερικού αίματος των χρόνιων ασθενών, όπως και η αναζήτηση πιθανού ανοσοτροποποιητικού ρόλου των Β λεμφοκυττάρων στους ασθενείς αυτούς. […

Inflammatory Complications in Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare inborn error of immunity that typically manifests with infectious complications. As the name suggest though, inflammatory complications are also common, often affecting the gastrointestinal, respiratory, urinary tracts and other tissues. These can be seen in all various types of CGD, from X-linked and autosomal recessive to X-linked carriers. The pathogenetic mechanisms underlying these complications are not well understood, but are likely multi-factorial and reflect the body’s attempt to control infections. The different levels of neutrophil residual oxidase activity are thought to contribute to the large phenotypic variations. Immunosuppressive agents have traditionally been used to treat these complications, but their use is hindered by the fact that CGD patients are predisposed to infection. Novel therapeutic agents, like anti-TNFa monoclonal antibodies, anakinra, ustekinumab, and vedolizumab offer promise for the future, while hematopoietic stem cell transplantation should also be considered in these patients

Therapeutic options for Burkholderia cepacia infections beyond co-trimoxazole: a systematic review of the clinical evidence

Burkholderia cepacia complex (BCC) is an important group of pathogens affecting patients with cystic fibrosis and chronic granulomatous disease as well as immunocompromised and hospitalised patients. Therapeutic options are limited owing to high levels of resistance of the organism, either intrinsic or acquired, to many antimicrobial agents. Co-trimoxazole (trimethoprim/sulfamethoxazole) has been a drug of choice. However, in some cases it cannot be administered because of allergic or hypersensitivity reactions, intolerance or resistance. We systematically searched for relevant publications including clinical data in PubMed and Scopus. The search identified 48 relevant case reports (57 cases) and 8 cohort studies or trials. Nineteen (33.3%) of 57 patients included in the case reports received ceftazidime-based regimens, 14 (73.7%) of whom were cured. Meropenem was administered in seven patients (12.3%), one (14.3%) of whom improved and five (71.4%) were cured. Seven (12.3%) of 57 cases were treated with penicillins, four of which were piperacillin (all had a favourable outcome). Based on the data reported in the eight relevant cohort studies or trials identified, favourable outcomes were observed in 68.4% (26/38) to 100% (16/16) of cases treated with ceftazidime and 66.7% (6/9) of cases treated with meropenem. Also, 9/12 (75%) of patients receiving penicillins improved. Thus, Ceftazidime, meropenem and penicillins, mainly piperacillin, either alone or in combination with other antimicrobial agents, may be considered as alternative options for BCC infections, according to the in vitro antimicrobial susceptibility patterns and clinical results. However, the available clinical data are not sufficient and further clinical experience is required to clarify the appropriateness of these antibiotics for BCC infections. (C) 2008 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved

The incidence of physician-diagnosed food allergy declines with age: A specialist UK centre experience

The incidence of physician-diagnosed food allergy declined with age in a cohort of UK adults.Men were more likely to be diagnosed with food allergy than women.The incidence of shellfish, wheat & cereals and vegetable & herb allergies increased with age

Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling

Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients