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Sökning: WFRF:(Cancrini C)

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  • Grimsholm, O., et al. (författare)
  • The Interplay between CD27(dull) and CD27(brig)(ht) B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory
  • 2020
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 30:9, s. 2963-
  • Tidskriftsartikel (refereegranskat)abstract
    • Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27(dull) and CD27(bright) MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27(du)(ll) and CD27(bright) MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27(du)(ll) into the CD27(bright) MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27(du)(ll) MBCs transit to the more differentiated CD27 bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27(du)(ll) clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27(du)(ll) MBCs that expand and differentiate in response to change.
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  • Lam, MT, et al. (författare)
  • A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function
  • 2019
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:12, s. 2778-2799
  • Tidskriftsartikel (refereegranskat)abstract
    • Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.
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