Mannose-binding lectin deficiency and predisposition to recurrent infection in adults.

Aims: The effects of mannose-binding lectin (MBL) deficiency are well known in children and in those with a compromised immune system. However, its effects in adults are debateable, with little research having been carried out in the UK regarding infection risk in otherwise healthy adults with an MBL deficiency.

Methods: Using an ELISA, we investigated the prevalence of MBL deficiency in both healthy adults and those with recurrent infection.

The utility of the ISAC allergen array in the investigation of idiopathic anaphylaxis.

A diagnosis of idiopathic anaphylaxis following a detailed clinical assessment remains very challenging for patients and clinicians. Risk reduction strategies such as allergen avoidance are not possible. This study investigated whether the (ISAC) allergen array with 103 allergens would add diagnostic value in patients with idiopathic anaphylaxis.

A UK national audit of hereditary and acquired angioedema.

Hereditary angioedema (HAE) and acquired angioedema (AAE) are rare life-threatening conditions caused by deficiency of C1 inhibitor (C1INH). Both are characterized by recurrent unpredictable episodes of mucosal swelling involving three main areas: the skin, gastrointestinal tract and larynx. Swelling in the gastrointestinal tract results in abdominal pain and vomiting, while swelling in the larynx may be fatal.

Immediate hypersensitivity to chlorhexidine is increasingly recognised in the United Kingdom.

Background: Chlorhexidine is widely used as an antiseptic agent. It is a potentially allergenic substance that can cause severe hypersensitivity reactions.

Objective: We describe six patients who had anaphylactic reactions attributed to chlorhexidine during surgery.

The RCPCH care pathway for children with urticaria, angio-oedema or mastocytosis: an evidence and consensus based national approach.

Aims: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies; the urticaria, angio-oedema or mastocytosis pathway is the fifth pathway. The pathways focus on defining the competences required to improve the equity of care received by children with allergic conditions.

Method: The urticaria, angio-oedema or mastocytosis pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence.

An approach to the patient with urticaria.

Patients 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.

Normal complement C4 values do not exclude hereditary angioedema.

This report describes a patient with hereditary angioedema (HAE) in whom complement C4 values were consistently normal. There was a family history of HAE, for which the patient had previously been screened, but in view of her normal C4 values she was deemed unaffected. However, at 10 years of age she presented with an eight month history of episodes of swelling affecting her hands and recurrent episodes of abdominal pain over the previous few months.

Allergy to local anaesthetic: the importance of thorough investigation.

A case report is presented which highlights the importance of a good history in arriving at the correct diagnosis in cases where allergy to local anaesthetic is suspected. Management of the patient is discussed and the topic of 'adverse reaction' briefly reviewed.

Atypical C-ANCA following high dose intravenous immunoglobulin.

Aims: (1) To assess a range of intravenous immunoglobulin products for atypical classical antineutrophil cytoplasmic antibody (C-ANCA) staining and to determine if this is present in patients treated with high dose intravenous immunoglobulin (2 g/kg/month) and replacement doses (200 mg/kg fortnightly); (2) using the United Kingdom national external quality assessment scheme (NEQAS), to determine if laboratories could differentiate this pattern from classical ANCA.

Methods: ANCA testing was performed on 30 batches of intravenous immunoglobulin from several manufacturers. Six patients treated with high dose intravenous immunoglobulin and 11 receiving replacement doses of immunoglobulin for hypogammaglobulinaemia were tested for ANCA by indirect immunofluorescence on cytospin preparations of ethanol fixed neutrophils and by enzyme linked immunosorbent assay (ELISA).

Biased T-cell receptor usage is associated with allelic variation in the MHC class II peptide binding groove.

A comprehensive analysis was carried out of the tri-molecular complex of peptide, major histocompatibility class II molecule, and T-cell receptor (TcR) involved in the recognition of the promiscuous HA (306-318) peptide, restricted by one of two closely related HLA-DR alleles, HLA-DRB1*0101 and HLA-DRB1*0103. These two DR molecules differ by only three amino acids at positions 67, 70, and 71, in the third variable region of the DRB1 chain. None of the HA (306-318)-specific T-cell clones restricted by these two DR molecules tolerated amino acid substitution at the peptide-binding position 71, despite the fact that the substitution did not interfere with peptide binding.

Antigen presentation by epithelial cells induces anergic immunoregulatory CD45RO+ T cells and deletion of CD45RA+ T cells.

The immunoregulatory effects of alloantigen presentation by tissue parenchymal cells to resting peripheral blood CD4+ T cells was investigated. Coculture of CD45RO+ (memory) and CD45RA+ (naive) T lymphocytes with primary cultures of MHC class II-expressing epithelial cells rendered both populations of T cells hyporesponsive to a subsequent challenge by the same MHC molecule expressed on EBV-transformed lymphoblastoid B cell lines. However, the mechanisms responsible for the allospecific hyporesponsiveness were distinct.

Heat retention using passive systems during anaesthesia: comparison of two plastic wraps, one with reflective properties.

Hypothermia during prolonged surgery may be prevented by active and passive warming methods. We have compared randomly two types of occlusive body wraps in groups of 20 patients. One wrap had additional reflective properties which, by reducing radiative in addition to convective and evaporative heat loss, was expected to improve heat conservation.

Peptide recognition by T-cell clones of an HLA-DRB1*1501/*0901 heterozygous donor is promiscuous only between parental alleles.

The HLA class II isotype and allelic restrictions of peptide recognition were analyzed with T cells from a DRB1*1501/DRB1*0901 heterozygous donor. Nineteen T cell clones, all directed against the single mycobacterial epitope p21-40 were tested with HLA homozygous lymphoblastoid cell lines as antigen-presenting cells. The most striking finding has been, that several DR isotype restricted clones recognized the peptide in the context of both parental, but not of unrelated alleles.

CD40lbase: a database of CD40L gene mutations causing X-linked hyper-IgM syndrome.

X-linked hyper-IgM syndrome (X-HIM) is an immunodeficiency caused by mutations in the gene encoding the CD40 ligand (CD40L). A database (CD40Lbase) of CD40L mutations has now been established, and the resultant information, together with other mutations reported elsewhere in the literature, is presented here.

Patient-controlled sedation for cataract surgery using peribulbar block.

Patients undergoing cataract surgery using peribulbar block were allocated randomly to self-administer doses of either midazolam 0.1 mg or propofol 3.3 mg without a lock-out facility; in the control group the syringe was charged with saline, not as a placebo, but to "blind" the surgeon and the nurse observer.

Comparison of helper and cytotoxic antirecipient T cell frequencies in unrelated bone marrow transplantation.

Donor/recipient histocompatibility antigen differences initiate acute graft-versus-host disease (GVHD) after bone marrow transplantation. Frequency analysis, using limiting dilution techniques, of functionally defined (helper or cytotoxic) antirecipient T lymphocyte precursors in the peripheral blood of the donor has been shown to be an accurate predictor for the development of moderate-to-severe acute GVHD. Here, we describe a sensitive assay for measuring alloreactive helper (IL-2-producing) T lymphocyte precursor (HTLp) frequencies, and compare the ability of this assay and the cytotoxic T lymphocyte precursor (CTLp) assay to detect HLA- class II and class I differences and to predict clinical outcome in a cohort of unrelated donor/recipient BMT pairs.

Adult onset immunodeficiency caused by inherited adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency is identified here as a cause of adult onset immunodeficiency. Two sisters who noted recurrent, predominantly chest infections in their twenties were found in their thirties to have CD4+ lymphopenia and lymphocyte ADA activity of approximately 5% of the lower limit of normal. Immune function, measured by proliferation of PBMCs in vitro to mitogens and specific Ags, was impaired.

Human T cells cannot act as autonomous antigen-presenting cells, but induce tolerance in antigen-specific and alloreactive responder cells.

The ability of two HLA-DR-expressing human T cell clones to function as antigen-presenting cells (APC) was investigated using highly purified T cells. The results demonstrated that these T cell clones are unable to act as autonomous APC, and that recognition of nominal or alloantigens on the surface of T cells leads to a state of nonresponsiveness. The first observation was that a T cell clone with specificity for the 306-324 peptide of influenza hemagglutinin (HA), and raised from a DR1 responder, exhibited apparent degeneracy of major histocompatibility complex restriction when cultured with peptide in the presence of peripheral blood mononuclear cells (PBMC) expressing a wide variety of structurally unrelated DR types.