Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency

Hauck, Fabian; Randriamampita, Clotilde; Martin, Emmanuel; Gérart, Stéphane; Lambert, Nathalie; Lim, Annick; Soulier, Jean; Maciorowski, Zofia; Touzot, Fabien; Moshous, Despina; Quartier, Pierre; Héritier, Sébastien; Blanche, Stéphane; Rieux-Laucat, Frédéric; Brousse, Nicole; Callebaut, Isabelle; Veillette, André; Hivroz, Claire; Fischer, Alain; Latour, Sylvain; Pïcard, Capucine

doi:10.1016/j.jaci.2012.07.029

Cited by 99 publications

(74 citation statements)

References 60 publications

(53 reference statements)

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“…According to the original model of immunoreceptor signaling, this initial ITAM phosphorylation is mediated by SFKs and is a prerequisite for Syk family kinase recruitment and activation (24). In the analogous situation of TCR, this model is well supported by the existing data (25)(26)(27). In B cells, the critical role of BCRassociated ITAMs has also been demonstrated (28).…”

mentioning

confidence: 83%

Nonredundant Roles of Src-Family Kinases and Syk in the Initiation of B-Cell Antigen Receptor Signaling

Štěpánek

Dráber

Drobek

et al. 2013

The Journal of Immunology

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When a BCR on a mature B cell is engaged by its ligand, the cell becomes activated, and the Ab-mediated immune response can be triggered. The initiation of BCR signaling is orchestrated by kinases of the Src and Syk families. However, the proximal BCR-induced phosphorylation remains incompletely understood. According to a model of sequential activation of kinases, Syk acts downstream of Src family kinases (SFKs). In addition, signaling independent of SFKs and initiated by Syk has been proposed. Both hypotheses lack sufficient evidence from relevant B cell models, mainly because of the redundancy of Src family members and the importance of BCR signaling for B cell development. We addressed this issue by analyzing controlled BCR triggering ex vivo on primary murine B cells and on murine and chicken B cell lines. Chemical and Csk-based genetic inhibitor treatments revealed that SFKs are required for signal initiation and Syk activation. In addition, ligand and anti-BCR Ab–induced signaling differ in their sensitivity to the inhibition of SFKs.

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mentioning

confidence: 83%

Nonredundant Roles of Src-Family Kinases and Syk in the Initiation of B-Cell Antigen Receptor Signaling

Štěpánek

Dráber

Drobek

et al. 2013

The Journal of Immunology

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“…Furthermore, certain T-cell signaling defects that may cause SCID or CID, such as ORAI-1, STIM-1, MAGT1, STK4, or LCK deficiencies as well as activating mutations of PI3KD, predispose to autoimmunity including cytopenias. 3,[28][29][30][31][32] Recently, loss of function of tripeptidyl peptidase 2 was demonstrated to cause ). In WAS, however, the basis of thrombocytopenia and microplatelets is the underlying cytoskeletal dysfunction.…”

Section: Autoimmune-mediated Cytopenia In Pidmentioning

confidence: 99%

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment

Seidel

2014

Blood

127

140

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Autoimmunity and immune dysregulation may lead to cytopenia and represent key features of many primary immunodeficiencies (PIDs). Especially when cytopenia is the initial symptom of a PID, the order and depth of diagnostic steps have to be performed in accordance with both an immunologic and a hematologic approach and will help exclude disorders such as systemic lupus erythematosus, common variable immunodeficiency, and autoimmune lymphoproliferative syndromes, hemophagocytic disorders, lymphoproliferative diseases, and novel differential diagnoses such as MonoMac syndrome (GATA2 deficiency), CD27 deficiency, lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency, activated PI3KD syndrome (APDS), X-linked immunodeficiency with magnesium defect (MAGT1 deficiency), and others. Immunosuppressive treatment often needs to be initiated urgently, which impedes further relevant immunologic laboratory analyses aimed at defining the underlying PID. Awareness of potentially involved disease spectra ranging from hematologic to rheumatologic and immunologic disorders is crucial for identifying a certain proportion of PID phenotypes and genotypes among descriptive diagnoses such as autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, severe aplastic anemia/refractory cytopenia, and others. A synopsis of pathomechanisms, novel differential diagnoses, and advances in treatment options for cytopenias in PID is provided to facilitate multidisciplinary management and to bridge different approaches.

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“…Lymphocyte-specific protein tyrosine kinase deficiency A single patient with homozygous lymphocyte-specific protein tyrosine kinase (LCK) mutation (OMIM# 153390) who suffered from recurrent infections and retinal vasculitis was identified by Hauck et al (2012).…”

Section: Stk-4 Deficiencymentioning

confidence: 99%

“…Autoantibodies to multiple self-antigens were present. The low number of Treg cells and the reduced activation-induced cell death of the patient's T cells might have contributed to the immune dysregulation (Hauck et al 2012). …”

Section: Stk-4 Deficiencymentioning

confidence: 99%

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Cardiovascular abnormalities in primary immunodeficiency diseases

et al. 2015

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In recent years, increasing numbers of patients with primary immune deficiency (PID) are being recognized as also suffering from cardiovascular system (CVS) abnormalities. These CVS defects might be explained by infectious or autoimmune etiologies, as well as by the role of specific genes and the immune system in the development and function of CVS tissues. Here, we provide the first comprehensive review of the clinical, potentially pathogenic mechanisms, and the management of PID, as well as the associated immune and CVS defects. In addition to some well-known associations of PID with CVS abnormalities, such as DiGeorge syndrome and CHARGE anomaly, we describe the cardiac defects associated with Omenn syndrome, calcium channel deficiencies, DNA repair defects, common variable immunodeficiency, Roifman syndrome, various neutrophil/macrophage defects, FADD deficiency, and HOIL1 deficiency. Moreover, we detail the vascular abnormalities recognized in chronic mucocutaneous candidiasis, chronic granulomatous disease, Wiskott-Aldrich syndrome, Schimke immuno-osseus dysplasia, hyper-IgE syndrome, MonoMAC syndrome, and X-linked lymphoproliferative disease. In conclusion, the expanding spectrum of PID requires increased alertness to the possibility of CVS involvement as an important contributor to the diagnosis and management of these patients.

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Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency

Cited by 99 publications

References 60 publications

Nonredundant Roles of Src-Family Kinases and Syk in the Initiation of B-Cell Antigen Receptor Signaling

Nonredundant Roles of Src-Family Kinases and Syk in the Initiation of B-Cell Antigen Receptor Signaling

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment

Cardiovascular abnormalities in primary immunodeficiency diseases

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