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Background: There is an increasing demand for specialist public allergy services across Ireland. Little data exist on the patterns of allergic disease in Irish adults. The limited resources available require innovative strategies to ensure quality care delivery. Aims: This study aimed to review the types of allergy referrals and diagnostic outcomes at a major Irish centre, and to establish an efficient method of communication with non-specialist practitioners. Methods: Demographic data, referral characteristics and diagnostic outcomes from one hundred consecutive new allergy referrals were identified. Additionally, communications to a pilot email service were reviewed over a 12-month period and user satisfaction assessed. Results: Requests for the investigation of food allergy accounted for 71 % of referrals. Despite this, the main diagnostic outcome in this cohort was a non-allergic condition, chronic spontaneous urticaria (56 %). immunoglobulin E (IgE)-mediated food allergy was definitively diagnosed in only 9 % of patients, with the majority of these presenting with anaphylaxis. The allergy advice email service received 43 requests for assistance over 12 months, mainly for help in the interpretation of an allergy clinical history. Feedback on the email service was universally positive. Conclusions: The majority of patients in this cohort did not have IgE-mediated allergic disease. Increased awareness of the features that differentiate allergy from non-allergic conditions such as food intolerance or chronic spontaneous urticaria is required. The allergy advice email service should be developed further to play a key role in education and care delivery in partnership primary care. [ABSTRACT FROM AUTHOR]

Chromosomal region 2q33 encodes the immune regulatory genes, CTLA4, ICOS and CD28, which are involved in regulation of T-cell activity and has been studied as a candidate gene locus in autoimmune diseases, including coeliac disease (CD). We have investigated whether an association exists between this region and CD in the Irish population using a comprehensive analysis for genetic variation. Using a haplotype-tagging approach, this gene cluster was investigated for disease association in a case–control study comprising 394 CD patients and 421 ethnically matched healthy controls. Several SNPs, including CTLA4_CT60, showed association with disease; however, after correction for multiple-testing, CTLA4−658C/T was the only polymorphism found to show significant association with disease when allele, genotype, or carrier status frequency were analysed (carrier status (Allele C), P=0.0016). Haplotype analysis revealed a haplotype incorporating the CD28/CTLA4 and two 5′ ICOS polymorphisms to be significantly associated with disease (patients 24.1%; controls 31.5%; P=0.035), as was a shorter haplotype composed of the CTLA4 markers only (30.9 vs 34.9%; P=0.042). The extended haplotype incorporating CD28/CTLA4 and 5′ ICOS is more strongly associated with disease than haplotypes of individual genes. This suggests a causal variant associated with this haplotype may be associated with disease in this population.Genes and Immunity (2006) 7, 19–26. doi:10.1038/sj.gene.6364265; published online 20 October 2005 [ABSTRACT FROM AUTHOR]

Celiac disease is caused by sensitivity to wheat gluten in genetically susceptible individuals. The etiological role of the other wheat-related cereals, barley, rye, and oats, is still debated. In order to investigate this issue further, in this study we examined the immune response of celiac mucosal T cell lines to fractions from all four cereals. Cell stimulation was assessed by measuring proliferation (employing (3)H-thymidine incorporation) or cytokine (IL-2, IFN-gamma) production. All five T cell lines demonstrated immunoreactivity to protein fractions from the four related cereals. In some cell lines, reactivity to wheat, barley, and rye was only evident when these cereal fractions had been pretreated with tissue transglutaminase. This study confirms the similar T cell antigenic reactivity of these four related cereals and has implications for their exclusion in the gluten-free diet. However, despite oats stimulation of T cell lines, this cereal does not activate a mucosal lesion in most celiac patients. [ABSTRACT FROM AUTHOR]

The above is by no means intended to be a comprehensive compendium of all currently available immunosuppressive therapies, but rather is designed to provide guidelines regarding some of the newer therapeutic options open to the clinician when faced with a patient with signs of a progressive and potentially destructive autoimmune process. It is worth noting that we are entering a period of rapid development with regard to our knowledge of the pathogenesis and underlying mechanisms of disease and one could envisage eventually categorizing autoimmune disease in terms of a specific immunological aberration and then administering an agent with selective action to correct the critical deficiency or imbalance. This goal may prove naive or unrealistic. [ABSTRACT FROM AUTHOR]

In any patient who suffers from frequent infections or from a clinical disorder caused by opportunistic organisms, the possibility of an underlying defect in immune defense should be considered. The purpose of this review is to outline a strategic approach towards screening for immunodeficiency in such patients. It should be apparent that the majority of serious immune deficiency states can be detected using a series of relatively simple and readily available investigations. The detection and further definition of other immunodeficiencies may require more sophisticated tests to be performed. The development of new biological tools now permits many of these disorders to be defined at the genetic and molecular level. Finally, early diagnosis of immunodeficiency is important, since it may permit the introduction of corrective measures which can reduce the morbidity and mortality of these disorders. [ABSTRACT FROM AUTHOR]

Of 2,782 sera submitted for autoanti body immunofluorescence screening, 32 were found to have antimitochondrial antibody (AMA) of the type associated with liver disease (M2/M4 pattern). Liver biopsies were obtained in 14 of these patients; 12 were found to have primary biliary cirrhosis (PBC) (Group A) whereas histological evidence of chronic active hepatitis was present in two others. The remaining 18 patients were not considered by the referring clinicians to have clinical evidence of PBC and consequently were not biopsied (Group B). [ABSTRACT FROM AUTHOR]

Circulating CD5 B-cell levels in 15 patients with rheumatoid arthritis (RA) not receiving remittive therapy was significantly increased when compared to 17 normal controls (mean±SE: RA, 19.7±2.85%; controls, 11.6±1.67%; P<0.02). In contrast, 24 patients with RA receiving gold sodium thiomalate therapy (GST) had similar CD5 B-cell levels (11.88±1.65) when compared to controls and significantly reduced levels when compared to the RA group not receiving remittive agents ( P<0.01). Furthermore, TCR γ T-cell levels were also assessed in these patients groups. These values were not significantly different between any of the groups (controls, 4.46±1.36%; GST, 6.88±1.73%; RA, 2.73±0.55%), although 42% of the GST treated group had γ T-cell levels higher than the entire untreated RA group. No correlation was observed between the levels of TCR γ T-cells and CD5 B-cells in any of these groups. These results suggested that therapy does influence the level of CD5 B-cells and γ T-cells in these patients. [ABSTRACT FROM AUTHOR]

Indomethacin, which is thought to exert its therapeutic effect by inhibiting the synthesis of PGE, is a commonly used first-line agent in the treatment of rheumatoid arthritis (RA). However, the effect of this drug on the humoral immune response in RA remains unclear. In this study, modulation of the in vitro synthesis of IgM and IgM-rheumatoid factor (RF) by indomethacin and prostaglandin E was examined in 11 patients with active RA and 10 normal controls. Indomethacin at a final concentration of 1 μg/ml significantly enhanced IgM production ( P<0.01) and RF production ( P<0.02) in Staphylococcus aureus Cowan I (SAC) stimulated RA cultures when compared to controls in whom no net enhancement effect was observed. In the patients, this increase in IgM production was more pronounced than the corresponding increase in RF synthesis ( P=0.078), suggesting that IgM and IgM-RF-secreting RA plasma cells have different susceptibilities to PGE mediated suppression. Nonetheless, addition of PGE (10 M final concentration) to the cultures inhibited IgM and RF production to a similar degree in the patient and control cultures. These findings demonstrate that PGE causes suppression of IgM and IgM auto-antibody production in vitro and that inhibition of endogenous PGE synthesis in RA patients treated with indomethacin results in a marked increase in the production of these antibodies. [ABSTRACT FROM AUTHOR]

IgM and IgA rheumatoid factor (RF) synthesis by synovial membrane mononuclear cells was measured in 14 patients with rheumatoid arthritis (RA). The results were compared with blood mononuclear cell cultures and correlated with the intensity of lymphocyte infiltration of the synovium. IgM RF was produced by all synovial cultures compared with 56% of blood cultures; IgA RF was produced by 86% of synovial cultures and by 21% of blood cultures. A correlation was observed between synovial IgM RF synthesis, but not IgA RF synthesis, and the intensity of T cell and B cell infiltration of the synovial membrane. [ABSTRACT FROM AUTHOR]

Osteoporosis frequently complicates coeliac disease but most studies focus on symptomatic patients at the time of diagnosis. Screening tests have revealed that many individuals with coeliac disease have mild, atypical, or absent symptoms. To evaluate the relationship between coeliac disease and osteopenia or osteoporosis in female subjects attending for bone densitometry. We studied 371 female subjects attending for bone densitometry, without secondary causes of osteoporosis and included those with normal and with reduced bone mineral density. Mineral density was measured by dual energy X-ray absorptiometry. Screening for coeliac disease was by measurement of anti-endomysial antibody by indirect immunofluorescence. Two of 115 (1.7%) female subjects with normal bone density and five of 256 (1.9%) female subjects with sub-normal bone density were positive for endomysial antibody. Five subjects who underwent small bowel biopsy had histological changes suggestive of coeliac disease. In females referred for bone densitometry, endomysial antibody positivity was not more prevalent among those with reduced bone mineral density. Examining only patients with clinically detected coeliac disease may overestimate the frequency of complications. This study does not support population screening for coeliac disease in an area with a high frequency of the condition. [ABSTRACT FROM AUTHOR]