Araştırma Çıktıları

Permanent URI for this communityhttps://hdl.handle.net/11443/931

Browse

Author: search.filters.author.Akcay, ArzuHas files: No

Search Results

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Hematopoietic Stem Cell Transplantation in Patients with Heterozygous STAT1 Gain-of-Function Mutation
    (SPRINGER/PLENUM PUBLISHERS, 2019-01-01) Kiykim, Ayca; Charbonnier, Louis Marie; Akcay, Arzu; Karakoc-Aydiner, Elif; Ozen, Ahmet; Ozturk, Gulyuz; Chatila, Talal A.; Baris, Safa
    PurposeHuman signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations present with a broad range of manifestations ranging from chronic mucocutaneous candidiasis and autoimmunity to combined immunodeficiency (CID). So far, there is very limited experience with hematopoietic stem cell transplantation (HSCT) as a therapeutic modality in this disorder. Here, we describe two patients with heterozygous STAT1 GOF mutations mimicking CID who were treated with HSCT.MethodsData on the HSC sources, conditioning regimen, graft-versus-host disease (GvHD) and antimicrobial prophylaxis, and the post-transplant course including engraftment, GvHD, transplant-related complications, infections, chimerism, and survival were evaluated. Pre- and post-transplant immunological studies included enumeration of circulating interferon gamma (IFN-)- and interleukin 17 (IL-17)-expressing CD4(+) T cells and analysis of IFN--induced STAT1 phosphorylation in patient 1 (P1)'s T cells.ResultsP1 was transplanted with cord blood from an HLA-identical sibling, and P2 with bone marrow from a fully matched unrelated donor using a reduced toxicity conditioning regimen. While P1 completely recovered from her disease, P2 suffered from systemic CMV disease and secondary graft failure and died due to severe pulmonary involvement and hemorrhage. The dysregulated IFN- production, suppressed IL-17 response, and enhanced STAT1 phosphorylation previously found in the CD4(+) T cells of P1 were normalized following transplantation.ConclusionHSCT could be an alternative and curative therapeutic option for selected STAT1 GOF mutant patients with progressive life-threatening disease unresponsive to conventional therapy. Morbidity and mortality-causing complications included secondary graft failure, infections, and bleeding.
  • No Thumbnail Available
    Item
    Sustained hyperferritinemia in a child with macrophage activation syndrome secondary to systemic juvenile idiopathic arthritis - perforinopathy: case based review
    (TURKISH J PEDIATRICS, 2018-01-01) Cakan, Mustafa; Aktay-Ayaz, Nuray; Gemici, Hakan; Annayev, Agageldi; Citak, Agop; Akcay, Arzu; Ozturk, Gulyuz
    Systemic juvenile idiopathic arthritis is a subtype of juvenile idiopathic arthritis and characterized by arthritis and many systemic features like fever, rash, hepatosplenomegaly, lymphadenopathy and serositis. Macrophage activation syndrome is the most dreadful complication of systemic juvenile idiopathic arthritis and can cause mortality and morbidity if not recognized and treated early and aggressively. Hemophagocytic lymphohistiocytosis (HLH) is characterized by diminished or absent activities of natural killer cells and cytotoxic T lymphocytes leading to cytokine storm and uncontrolled activation of T cells and macrophages. Primary (familial) HLH is a group of autosomal recessive disorders caused by mutations in the perforin and other related genes and distinctive for onset during early infancy and high rate of mortality. Secondary HLH may be caused by infectious, oncologic and rheumatologic disorders. The term Perforinopathy is used to describe cases with classical familial HLH and also for cases with familial HLH gene mutations but not following a classical familial HLH course. Herein we report a case of chronic perforinopathy in which clinical symptoms started with systemic juvenile idiopathic arthritis and severe macrophage activation syndrome that needed plasma exchange and extracorporeal membrane oxygenation during acute period and ongoing interleukin-1 blockage for sustained hyperferritinemia.