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Basics of Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Rafeul Alam, Dipa K Sheth, Magdalena M Gorska
Patients with congenital deficiency of Lck have severe combined immunodeficiency because of the failure of CD4 differentiation; ZAP70 deficiency results in the severe defect of CD8 T cell differentiation (see Chapter 12).
Molecular and Cellular Pathogenesis of Systemic Lupus Erythematosus
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
George C. Tsokos, Yuang-Taung Juang, Christos G. Tsokos, Madhusoodana P. Nambiar
The hypothesis that other members of the ζ chain family, such as Fc epsilon receptor type I gamma (FceRIy) chain, may substitute for the deficient T cell receptor ζ chain, has been investigated by Enyedy et al.29 Immunoprecipitation/immunoblotting and confocal microscopy experiments demonstrated that a large proportion of SLE T cells express very high levels of FceRTv chain that is functionally associated with the T cell receptor and takes part in antigen receptor mediated signal transduction. Expression of FceRIy, in lieu of T cell receptor ζ chain, has been reported in mouse large granular lymphocytes.30 T lymphocytes from tumor-bearing mice expressed T cell receptor that completely lacked T cell receptor ζ chain and was replaced by FceRIy chain.31 Also, T cell receptor ζ deficient mice have been shown to express FceRIy chain as part of the T cell receptor -γδ complex.32-34 Unlike T cell receptor ζ chain, which mediates signaling through zeta chain-associated protein-70 (ZAP-70), Fc epsilon receptor type I gamma chain mediates signaling by associating with 100-fold more potent phosphorylated protein spleen tyrosine kinase (SyK).35,36 Presently, it is unknown whether SyK is upregulated in SLE T cells and FceRIy chain signal transduction occurs by associating with SyK or other downstream signaling molecules. High-level expression of tyrosine kinase activity and alternative antigen receptor mediated signaling has been described in T cells of patients with ZAP-70 deficiency37 Overexpression of the FceRIy gamma chain in normal T cells also leads to increased T cell receptor/CD3 mediated intracellular calcium response suggesting that the single immunotyrosine activation motif in the FceRIy chain, compared to the three in T cell receptor ζ chain, does not hinder the level of intracellular calcium response. The high level expression of FceRIy chain could replace the defective T cell receptor ζ chain and contribute to the aberrant antigen receptor-initiated signaling in SLE T cells.
Clinical and Mutation Description of the First Iranian Cohort of Infantile Inflammatory Bowel Disease: The Iranian Primary Immunodeficiency Registry (IPIDR)
Published in Immunological Investigations, 2021
Farzaneh Rahmani, Elham Rayzan, Mohammad Reza Rahmani, Sepideh Shahkarami, Samaneh Zoghi, Arezoo Rezaei, Zahra Aryan, Mehri Najafi, Meino Rohlfs, Tim Jeske, Majid Aflatoonian, Zahra Chavoshzadeh, Fatemeh Farahmand, Farzaneh Motamed, Pejman Rohani, Hossein Alimadadi, Alireza Mahdaviani, Mahboubeh Mansouri, Marzieh Tavakol, Mirjam Vanderberg, Daniel Kotlarz, Christoph Klein, Nima Rezaei
The product of ZAP70 gene, ZAP-70, is essential for T cell receptor (TCR) signal transduction and is expressed predominantly on natural killer cells and T cell (Chan et al. 2016). ZAP-70 deficiency is characterized by the absence of CD8 + T cells in the periphery, defective TCR signalling in CD4+ cells, and defective T cell tolerance induction, the latter being cited for autoimmune manifestations in these patients (Liu et al. 2017). Importantly, the presence of IBD in patients with ZAP70 mutation is associated with a leaky SCID phenotype with residual CD4 + T cell activity (Liu et al. 2017). Single nucleotide variants of ZAP70 have been found to affect IBD risk in some populations (Bouzid et al. 2013). Our patient had low CD8+ counts, recurrent thrush and a CD phenotype and unfortunately died due to complications of candidemia at 14 months old.