In rat basophilic leukemia 2H3 (RBL-2H3) cells, mAb AA4 binds to two derivatives of ganglioside GD1b that associate with the Src family kinase p5356lyn and a serine kinase. Pre-incubation of cells with mAb AA4 blocks immunoglobulin E (IgE) mediated histamine release. In the present study we investigated the effect of incubation with mAb AA4 on signal transduction events. In addition to stimulation of the high affinity IgE receptor (FcεRI), cells were also activated by the calcium ionophore A23187 and the acetylcholine agonist carbachol in RBL-2H3 cells transfected with the G protein-coupled m3 muscarinic receptor. Incubation of cells with mAb AA4 in a dose-dependent manner inhibited the following FcεRI-induced signal transduction events: the increase of intracellular free calcium, phosphoinositol breakdown, tyrosine phosphorylation of proteins including the β- of FcεRI and secretion. However, there was no inhibition of degranulation or of these biochemical events when cells were stimulated with calcium ionophore or activated via a G protein-coupled pathway. Our results demonstrate that mAb AA4 selectively blocks FcεRI-induced cell activation at a very early step upstream of receptor tyrosine phosphorylation. As mAb AA4 has previously been found to bind to gangliosides associated with FcεRI, inhibition of very early biochemical events may be due to interaction of mAb AA4 with the FcεRI induced signal transduction cascade at the receptor level.

X-linked severe combined immunodeficiency is a recessive hereditary disease characterized by severe and persistent infections starting in the first months of life and associated with diarrhea and failure to thrive.1 Affected infants almost invariably present with an absence of T cells and natural killer cells, normal or elevated B-cell counts, and hypogammaglobulinemia. This disease is rapidly fatal without bone marrow transplantation.2 The disease locus has been mapped to Xq12–13,3 and the genetic defect identified as a mutation of the γ chain of the interleukin-2 receptor,4 which has been cloned and was recently renamed the common γ (γc) chain because of . . .

From a community‐based study cohort of 1812 elementary schoolchildren we selected 129 unrelated participants to investigate the relevance of HLA‐class II molecules (DPB, DQB, and DRB) to the regulation of immune response to the mite allergen Der p 1 and to clinical atopic disorders. On the basis of skin prick test results validated by measurement of specific IgE, individuals were selected and divided into three groups: group I (n = 20), controls without detectable specific IgE to common inhalant allergens; group II (n = 22), children sensitized only to non‐mite allergens; group III (n = 85), children sensitized to Der p 1. Clinical history of asthma, eczema, and hay fever was ascertained using standardized questionnaires. In total, 43 different HLA class II alleles (DPB, n = 19; DQB, n = 14; and DRB, n = 10) were determined by sequence‐specific oligonucleotide typing with PCR‐amplified DNA. We were not able to demonstrate significant differences in gene frequencies of any HLA class II allele between the group of mite‐sensitized children and one of the other two groups. However, the presence of certain DRB‐ and DPB‐haplotypes (DRB *0100/*0300/*1100 and DPB *0201/*0401) was significantly associated (p < 0.01) with a history of asthma, hay fever, and atopy (defined as a history of asthma and/or hay fever and/or eczema). Other haplotypes, including DQB *0303/*0503, DRB *0200/*0700, and DPB 0402 were negatively associated with a history of eczema, hay fever, and atopy (p < 0.01). Thus, our findings do not suggest a relevance of HLA‐class II molecules to mite allergy; however, some HLA class n haplotypes appear to be predictive of the incidence of atopic disorders.

A case of severe combined immunodeficiency (SCID) in monozygotic twin sisters was detected at 3 months of age with neutropenia in one twin and a normal differential count in the other. The neutropenic twin, suffering from severe skin ulcers, was successfully treated with granulocyte colony stimulating factor (G-CSF). Discordant occurrence of neutropenia in identical twins shows that there may be a non-genetic cause for the neutropenia in SCID. Suppression of myelopoiesis was probably induced by activated maternal T cells. The neutropenia in this case may thus be classified as SCID associated neutropenia, as opposed to reticular dysgenesis, in which the neutropenia is G-CSF refractory and is most probably caused by a genetic stem cell defect. A response to G-CSF in a neutropenic child with SCID can be clinically beneficial and might help to distinguish between G-CSF unresponsive reticular dysgenesis and G-CSF responsive SCID associated neutropenia.

In a 2,5 year-old girl admitted because of persisting cough, physical examination revealed decreased breathing sounds over the entire left lung. Chest x-ray showed a unilaterally hyperlucent left lung. Bronchoscopy revealed no evidence of foreign body aspiration and bronchography demonstrated saccular dilatations and pruned tree images of the left bronchi. Angiocardiography showed normal anatomy of the pulmonary vessels but decreased perfusion of the left lung. These findings combined establish the diagnosis of Mc-Leod-Swyer-James-Syndroms a condition due to post-infectious bronchiolitis obliterans.

A 3 year old Turkish girl is described who was suffering from major histocompatibility complex (MHC) class II deficiency syndrome, which is characterised by the lack of expression of HLA class II antigens on mononuclear cells. The presence of HLA class II genes was demonstrable at the DNA level. Combined immunodeficiency was indicated by hypogammaglobulinaemia and the absence of delayed type hypersensitivity on skin testing. Further, she was unable to produce specific antibodies towards foreign antigens and suffered from recurrent pulmonary, gastrointestinal, and septic infections from the third month of life. The clinical course was complicated by a Coombs test positive haemolytic anaemia due to the production of autoantibodies against the rhesus "e' antigen, a non-glycosylated protein antigen. Haemolysis could be controlled by oral steroid treatment. This case is of interest as it shows that despite the absence of HLA class II antigens and combined immunodeficiency autoimmune reactions with production of specific autoantibodies directed to protein antigens are possible.