Contributions
Abstract: PB2022
Type: Publication Only
Background
Common immunological features in patients with interleukin-2-inducible T-cell kinase (ITK) deficiency include: CD4 + T cell loss along with absolute lymphopenia and progressive hypogammaglobulinemia. iNKT cells are severely reduced in the peripheral blood of ITK deficient patients; hence a critical role has been postulated for iNKT cells in the response to EBV infection.
Aims
Herein we report a child with a novel ITK mutation who showed impaired peripheral blood innate lymphoid cells, and Th-17 related IL-17A, IL-22, and GM-CSF cytokine production.
Methods
A Previously healthy (5 year old ?) patient, from a consanguineous family was admitted to the hospital with complaints of unilateral swelling on of the neck. Biopsy was compatible with Hodgkin lymphoma and she was treated with ABVD/COPP protocol, but she experienced an early relapse just one year after completing chemotherapy. ICE regimen followed by autologous transplantation was performed. After transplantation she had hypogammaglobulinemia and persistent and fatal EBV infection. Next generation sequencing returned a homozygous frame-shift variant in ITK (LRG_189t1: c.328delA: p. Thr110Argfs Ter1551.) The variant was confirmed by Sanger sequencing and segregated with the disease. This variant has not been previously described. but variants in ITK are described to cause lymphoproliferative syndrome with splenomegaly and hepatomegaly, as well as anemia, thrombocytopenia and pancytopenia. We report impaired CD3/CD28 induced proliferation by T cells. Itk mutant cells were more apoptotic without or upon TCR activation. Additionally, T cells produced less IL-17A, IL-22, and GM-CSF. Conversely, IFN-γ production was increased. Lastly, we analyzed peripheral ILC populations and observed reduced ILC3.
Results
Although it has previously been reported that TH-17 cytokine levels are impaired in ITK deficient mice, we report for the first time that peripheral blood innate lymphoid cells, and Th-17 related cytokine production are impaired in a child with a novel ITK mutation.
Conclusion
.
Session topic: 17. Hodgkin lymphoma – Clinical
Keyword(s): Hodgkin's Lymphoma, Immunodeficiency
Abstract: PB2022
Type: Publication Only
Background
Common immunological features in patients with interleukin-2-inducible T-cell kinase (ITK) deficiency include: CD4 + T cell loss along with absolute lymphopenia and progressive hypogammaglobulinemia. iNKT cells are severely reduced in the peripheral blood of ITK deficient patients; hence a critical role has been postulated for iNKT cells in the response to EBV infection.
Aims
Herein we report a child with a novel ITK mutation who showed impaired peripheral blood innate lymphoid cells, and Th-17 related IL-17A, IL-22, and GM-CSF cytokine production.
Methods
A Previously healthy (5 year old ?) patient, from a consanguineous family was admitted to the hospital with complaints of unilateral swelling on of the neck. Biopsy was compatible with Hodgkin lymphoma and she was treated with ABVD/COPP protocol, but she experienced an early relapse just one year after completing chemotherapy. ICE regimen followed by autologous transplantation was performed. After transplantation she had hypogammaglobulinemia and persistent and fatal EBV infection. Next generation sequencing returned a homozygous frame-shift variant in ITK (LRG_189t1: c.328delA: p. Thr110Argfs Ter1551.) The variant was confirmed by Sanger sequencing and segregated with the disease. This variant has not been previously described. but variants in ITK are described to cause lymphoproliferative syndrome with splenomegaly and hepatomegaly, as well as anemia, thrombocytopenia and pancytopenia. We report impaired CD3/CD28 induced proliferation by T cells. Itk mutant cells were more apoptotic without or upon TCR activation. Additionally, T cells produced less IL-17A, IL-22, and GM-CSF. Conversely, IFN-γ production was increased. Lastly, we analyzed peripheral ILC populations and observed reduced ILC3.
Results
Although it has previously been reported that TH-17 cytokine levels are impaired in ITK deficient mice, we report for the first time that peripheral blood innate lymphoid cells, and Th-17 related cytokine production are impaired in a child with a novel ITK mutation.
Conclusion
.
Session topic: 17. Hodgkin lymphoma – Clinical
Keyword(s): Hodgkin's Lymphoma, Immunodeficiency