Show simple item record

dc.contributor.authorImai, K
dc.contributor.authorCatalan, N
dc.contributor.authorPlebani, A
dc.contributor.authorMarodi, L
dc.contributor.authorOzden, S
dc.contributor.authorKumaki, S
dc.contributor.authorNagendran, V
dc.contributor.authorWood, P
dc.contributor.authorGlastre, C
dc.contributor.authorSarrot-Reynauld, F
dc.contributor.authorHermine, O
dc.contributor.authorForveille, M
dc.contributor.authorRevy, P
dc.contributor.authorFischer, A
dc.contributor.authorDurandy, A
dc.date.accessioned2019-12-10T10:38:45Z
dc.date.available2019-12-10T10:38:45Z
dc.date.issued2003
dc.identifier.issn0021-9738
dc.identifier.urihttps://doi.org/10.1172/JCI200318161
dc.identifier.urihttp://hdl.handle.net/11655/14076
dc.description.abstractHyper-IgM syndrome (HIGM) is a heterogeneous condition characterized by impaired Ig class-switch recombination (CSR). The molecular defects that have so far been associated with this syndrome which affect the CD40 ligand in HIGM type 1 (HIGN1), CD40 in HIGM3, and activation-induced cytidine deaminase (AID) in HIGM2 - do not account for all cases. We investigated the clinical and immunological characteristics of 15 patients with an unidentified form of HIGM. Although the clinical manifestations were similar to those observed in HIGM2, these patients exhibited a slightly milder HIGM syndrome with residual IgG production. We found that B cell CSR was intrinsically impaired. However, the generation of somatic hypermutations was observed in the variable region of the 19 heavy chain gene, as in control B lymphocytes. In vitro studies showed that the molecular defect responsible for this new HIGM entity (HIGM4) occurs downstream of the AID activity, as the AID gene was induced normally and AID-induced DNA double-strand breaks in the switch mu region of the Ig heavy chain locus were detected during CSR as normal. Thus, HIGM4 is probably the consequence of a selective defect either in a CSR-specific factor of the DNA repair machinery or in survival signals delivered to switched B cells.
dc.language.isoen
dc.publisherAmer Soc Clinical Investigation Inc
dc.relation.isversionof10.1172/JCI200318161
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectResearch & Experimental Medicine
dc.titleHyper-Igm Syndrome Type 4 With A B Lymphocyte-Intrinsic Selective Deficiency In Ig Class-Switch Recombination
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalJournal Of Clinical Investigation
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume112
dc.identifier.issue1
dc.identifier.startpage136
dc.identifier.endpage142
dc.description.indexWoS
dc.description.indexScopus


Files in this item

This item appears in the following Collection(s)

Show simple item record