scholarly journals Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells.

1994 ◽  
Vol 91 (20) ◽  
pp. 9466-9470 ◽  
Author(s):  
J. P. DiSanto ◽  
F. Rieux-Laucat ◽  
A. Dautry-Varsat ◽  
A. Fischer ◽  
G. de Saint Basile
Keyword(s):  
T Cells ◽  
X Chromosome ◽  
Severe Combined Immunodeficiency ◽  
Interleukin 2 ◽  
Combined Immunodeficiency ◽  
Gamma Chain ◽  
Interleukin 2 Receptor ◽  
Peripheral T Cells

Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4090-4097 ◽  
Author(s):  
Carsten Speckmann ◽  
Ulrich Pannicke ◽  
Elisabeth Wiech ◽  
Klaus Schwarz ◽  
Paul Fisch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Severe Combined Immunodeficiency ◽  
Interleukin 2 ◽  
Intrinsic Defect ◽  
Combined Immunodeficiency ◽  
Gamma Chain ◽  
Cell Repertoire ◽  
Hematopoietic Stem ◽  
Susceptibility To Infection

Abstract X-linked severe combined immunodeficiency is a life-threatening disorder caused by mutations in the gene encoding the interleukin-2 receptor gamma chain (IL2RG). Hypomorphic mutations and reversion of mutations in subpopulations of cells can result in variant clinical phenotypes, making diagnosis and treatment difficult. We describe a 5-year-old boy with mild susceptibility to infection who was investigated for a mutation in IL2RG due to persistent natural killer (NK)– and T-cell lymphopenia. A functionally relevant novel T466C point mutation was found in B, NK, and epithelial cells, whereas α/β and γ/δ T cells showed the normal gene sequence, suggesting reversion of the mutation in a common T-cell precursor. This genetic correction in T cells resulted in a diverse T-cell repertoire and significant immunity despite failure to produce specific antibodies linked to an intrinsic defect of mutant B cells. These observations confirm the potential of revertant T-cell precursors to reconstitute immune function, but questions remain on the longevity of revertant cells implicating the need for careful follow up and early consideration of hematopoietic stem cell transplantation (HSCT).

Interleukin-2 receptor common gamma chain (IL2RG) defects present a diagnostic challenge

2018 ◽  
Vol 5 (4) ◽  
pp. 130-134
Author(s):  
Caroline Weisser ◽  
Dennis E. Bulman ◽  
Kayla Flamenbaum ◽  
Maian Roifman
Keyword(s):  
Genetic Analysis ◽  
Severe Combined Immunodeficiency ◽  
Genetic Defect ◽  
Interleukin 2 ◽  
Combined Immunodeficiency ◽  
Gamma Chain ◽  
Gene Encoding ◽  
Common Gamma Chain ◽  
Interleukin 2 Receptor ◽  
The Common

Background: The protein encoded by interleukin-2 receptor common gamma chain (IL2RG) is an important signaling component of many interleukin receptors, including those of interleukin-2, -4, -7, and -21, known as the common gamma chain. Mutations in the gene encoding the common gamma chain of the interleukin-2 receptor cause X-linked severe combined immunodeficiency (SCID). In this report, we present an unknown genetic defect of a patient diagnosed with SCID whose genetic analysis was performed 2 decades later. Methods: Whole genome sequencing and Sanger confirmation were used to identify a novel frameshift mutation in IL2RG. Massively parallel sequencing of genes associated with SCID were performed on the patient’s mother and sister. Results: Next generation sequencing techniques identified a heterozygous frame-shift deletion in the gene encoding the common gamma chain of IL2RG in our patient. The patient’s mother had a low level mosaicism for the same deletion. The sister had no detectable deletion. Conclusion: We have identified a novel mutation in IL2RG resulting in an X-linked SCID phenotype. The genetic analysis of the patient’s mother revealed a mosaicism which was not passed on to his sister. The importance of genetic analysis in family members and SCID patients with an unknown genetic defect should be emphasized for family planning and subsequent genetic counseling. Statement of novelty: Genetic testing is an extremely important component in evaluating severe combined immunodeficiency as it impacts treatment course and prognosis, and allows for genetic analysis and counselling of family members.

Interleukin-2 Receptor Subunit Expression and Function on Human Peripheral T Cells Is Not Dependent on the Anticoagulant

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2989-2993 ◽  
Author(s):  
Guido L. Vanham ◽  
Godelieve Penne ◽  
Chris Vereecken ◽  
Johan Vingerhoets ◽  
Luc Kestens
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
Receptor Subunit ◽  
Interleukin 2 Receptor ◽  
Peripheral T Cells ◽  
Subunit Expression ◽  
And Function

Interleukin-2 Receptor Subunit Expression and Function on Human Peripheral T Cells Is Not Dependent on the Anticoagulant

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2989-2993
Author(s):  
Guido L. Vanham ◽  
Godelieve Penne ◽  
Chris Vereecken ◽  
Johan Vingerhoets ◽  
Luc Kestens
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
Receptor Subunit ◽  
Interleukin 2 Receptor ◽  
Peripheral T Cells ◽  
Subunit Expression ◽  
And Function

scholarly journals Absence of interleukin 2 production in a severe combined immunodeficiency disease syndrome with T cells.

1990 ◽  
Vol 171 (5) ◽  
pp. 1697-1704 ◽  
Author(s):  
J P DiSanto ◽  
C A Keever ◽  
T N Small ◽  
G L Nicols ◽  
R J O'Reilly ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Severe Combined Immunodeficiency ◽  
T Cell Development ◽  
Interleukin 2 ◽  
Combined Immunodeficiency ◽  
Alternative Pathways ◽  
Immunodeficiency Disease ◽  
Severe Combined Immunodeficiency Disease ◽  
Subtle Abnormality

We have characterized a child with a severe combined immunodeficiency disease syndrome with increased numbers, but a normal distribution, of CD3+ T cells. This patient's immunological defect appears to be attributable to a selective deficiency in T cell production of IL-2, which may reflect a subtle abnormality in the IL-2 gene locus or a defect in a regulatory factor necessary for IL-2 transcription. The increased numbers of phenotypically normal T cells in this patient suggest that alternative pathways of T cell development exist in man or that IL-2 production intra- and extrathymically is controlled via distinct regulatory mechanisms.

scholarly journals Expression of the interleukin-2 receptor gamma chain on cord blood mononuclear cells

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3344-3350 ◽  
Author(s):  
S Saito ◽  
T Morii ◽  
H Umekage ◽  
K Makita ◽  
K Nishikawa ◽  
...  
Keyword(s):  
T Cells ◽  
Cord Blood ◽  
Nk Cells ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Gamma Chain ◽  
Blood Lymphocytes ◽  
Interleukin 2 Receptor ◽  
Significant Difference ◽  
Cord Blood Lymphocytes

Lymphocytes in umbilical cord blood and neonatal peripheral blood have been shown to have less ability in an immune reaction. In our present experimental approach to address this issue, we made use of the cord blood of full-term birth infants to investigate the expression of the interleukin- 2 receptor gamma (IL-2Rgamma) chain that is shared with receptors for IL-4, IL-7, IL-9, and IL-15 as well as IL-2. The gamma chain expression in cord blood lymphocytes was about one-third that in the lymphocytes of adults, whereas no significant difference between cord blood and adult monocytes was observed. A reduced expression of the gamma chain was observed in all of the CD4+ T cells, CD8+ T cells, gamma-delta T cells, B cells, CD16+ natural killer (NK) cells, and CD56(bright) NK cells of the cord blood lymphocytes. The reduced gamma chain expression reached two-thirds of that in adults after 3 days of culture in vitro and in infants 3 days after birth, thus implying that the increase in the gamma chain may significantly contribute to the prevention of neonatal infection.

Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1872-1875 ◽  
Author(s):  
Taizo Wada ◽  
Masahiro Yasui ◽  
Tomoko Toma ◽  
Yuko Nakayama ◽  
Mika Nishida ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Severe Combined Immunodeficiency ◽  
Phenotypic Expression ◽  
Splice Site Mutation ◽  
Skin Lesions ◽  
Omenn Syndrome ◽  
Combined Immunodeficiency ◽  
Site Mutation ◽  
Gamma Chain

Abstract X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (γc) and usually characterized by the absence of T and natural killer (NK) cells. Here, we report an atypical case of XSCID presenting with autologous T and NK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G>A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual γc expression and development of T and NK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.

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