M E Conley

..These studies indicate that 90%-95% of males with presumed XLA have mutations in Btk. The other patients are likely to have defects in other genes...

..Distinguishing between these two types of gene defects is essential for informative genetic counseling...

..These findings indicate that even a modest decrease in Btk function can impair B cell proliferation or survival. However, a mutation in Btk and reduced numbers of B cells are not always associated with clinical disease...

..Splenectomy was used more sparingly. Stem cell transplant was more likely to be used in centers providing care for 10 or more patients. Studies that better define prognostic markers and optimal therapy are needed...

..Recent clinical studies in patients with genetically proven X-linked or autosomal recessive agammaglobulinemia provide some guidelines that should influence our management of patients with suspected immunodeficiency...

..Polymorphic variants in the components of the pre-B cell and B-cell receptor complex, particularly micro heavy chain and lambda5, may contribute to the severity of XLA...

..A better understanding of the factors that make this site vulnerable will shed light on the mechanisms of LINE-1 mediated insertional mutagenesis...

..These results are consistent with an X-linked form of SCID, due to the loss of regulatory elements that control the response to hypoxia in hematopoietic cells...

..Three friends with an interest in both the clinical and scientific aspects of primary immunodeficiency carried out a discussion or trialogue to address some of these issues...

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..Identifying the genetic and environmental factors that influence the clinical phenotype may enhance patient care and our understanding of normal B cell development...

..Not all genes responsible for immunodeficiency have been identified. As many as 20 to 30% of patients with clinical and laboratory evidence of single gene defects of the immune system do not fit any well described clinical disorder...

..These findings suggest that requirements for signaling through the pre-BCR are more stringent in the human compared to the mouse. Possible explanations for this observation are discussed...

..The immune system and overall growth and development were otherwise normal in this patient, suggesting that BLNK function is highly specific...

..These studies document the utility of SSCP analysis for both mutation detection and carrier detection in X-linked hyper IgM syndrome...

..These findings are most consistent with the mutations originating in a male gamete with different mutations on the two strands of DNA, a bichromatid mutation...

..Although 24 polymorphic variants of this gene were found in 35 patients, we did not identify any alterations that were likely to be the cause of disease...

..Furthermore, they suggest that Igalpha does not play a critical role in B-cell development until it is expressed, along with mu heavy chain, as part of the pre-BCR...

..However, none of the alterations appeared to be associated with disease in the patients screened...

..It will also be useful in diagnostic studies, including carrier detection, and in studies directed towards gene therapy or gene replacement...

..We conclude that Tec is expressed and can be stimulated throughout human B-cell differentiation, implying that this tyrosine kinase plays a role in B-cell development and activation...

..These results suggest that some mu heavy chains elicit negative selection at the pro-B cell to pre-B cell transition...

..1. These findings indicate that expression of the functional lambda5/14.1 is critical for B cell development in the human...

..These studies document the considerable variability in the Btk mutations causing XLA and they demonstrate an approach that will be useful for carrier detection as well as mutation identification...

..Lymphoid hyperplasia was seen in patients with hyper IgM syndrome and normal AID as well as the patients with hyper IgM syndrome and defects in AID...

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..It will be interesting to determine whether the protein encoded by this gene interacts with the pre-B cell receptor signal transduction pathway or is involved in a new pathway...

..Immune complex deposition in the subepithelial zone of glomerular capillaries can lead to membranous glomerulopathy...

..Donor lymphocytes, including CD8 cells, appeared to markedly reduce the RSV load but increased the pulmonary symptoms. Immunosuppressive therapy ameliorated lung disease but allowed the RSV load to rebound...

..Recognition of EBV-induced ocular disease as an initial presentation of clinical EBV infection is important to the practitioner because of the ubiquitous nature of this herpesvirus...

..It is likely that successful engraftment will require more aggressive immunosupressive medications...

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..The results of the current study suggest that although the disease impacts the daily lives of adults with XLA, they still become productive members of society and excel in many areas...

..The results show that minor changes in the ability of the Igalpha/Igbeta complex to bring the BCR to the cell surface have profound effects on B cell development...

..Our study indicates that at least 20-30% of patients with autosomal recessive defects in B cell development have mutations in the micro heavy chain...

..These results suggest that myelotoxic drugs may not be needed to achieve B cell engraftment in B-cell-deficient subjects...

..In addition to Epstein-Barr virus encephalitis, CNS lymphoproliferative disease, and lymphoma, this patient also developed MR angiographic evidence of diffuse fusiform aneurysmal dilation of intracranial vessels...

..These results indicate that most adults with XLA are moderately healthy and lead productive lives...

..carinii and 1 cytomegalovirus), 2 of encephalitis (1 ECHO virus and 1 cytomegalovirus), 2 of malignancy (both hepatocellular carcinoma), 1 of sclerosing cholangitis caused by Cryptosporidium, and 1 of hemolytic uremic syndrome...

..As a result of this work, new entities have been included, and the nomenclature of some PIDs (specifically of the various forms of class-switch recombination defects, previously known as hyper-IgM syndromes) has been changed...

..In its last meeting in Jackson Hole, Wyo, after 3 days of intense scientific presentations and discussions, the committee has updated the classification of PID, as reported in this article...

..It is therefore proposed that these IgM(+)IgD(+)CD27(+) B cells provide the splenic marginal zone with a diversified and protective preimmune repertoire in charge of the responses against encapsulated bacteria...

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