scholarly journals Establishing reference ranges for lymphocyte proliferation responses to phytohemagglutinin in patients with T cell dysfunction

2019 ◽  
Vol 6 (1) ◽  
pp. 26-30
Author(s):  
Mohammad Alsalamah ◽  
Linda Vong ◽  
Lorand Cimpean ◽  
Harjit Dadi
Keyword(s):  
T Cell ◽  
Lymphocyte Proliferation ◽  
Stimulation Index ◽  
Severe Combined Immunodeficiency ◽  
Control Group ◽  
Reference Ranges ◽  
Healthy Controls ◽  
Combined Immunodeficiency ◽  
Lymphocyte Proliferation Response ◽  
Wide Range

Introduction: The evaluation of lymphocyte proliferation responses is a critical component of the clinical work up for patients with suspected immunodeficiencies. Those with severe combined immunodeficiency (SCID) have consistently low to absent responses (stimulation index, SI) to the mitogen phytohemagglutinin (PHA). However, patients with combined immunodeficiency (CID) have more varied proliferative responses, and are open to a wide range of interpretations. Aims: To establish lymphocyte proliferation response reference ranges for patients with T cell defects, especially those with CID as well as healthy controls. Methods: Data was collected retrospectively from charts of patients with a diagnosis of SCID (n = 39), CID (n = 52), or from healthy controls (n = 440). Reference percentiles were calculated using the 95% of the distribution of the test results. Results: The reference ranges for the control group ranged from 134 to 2220.5, whereas those with CID were distributed between 0.81 and 169.1. Patients with typical SCID had profound low proliferative responses, with SI <5. Conclusion: Our results highlight the variability of lymphocyte proliferation responses to PHA in patients with CID as well as healthy controls. These reference ranges will assist with the critical interpretation of assay results, particularly when values fall on the extreme end of the range. Statement of novelty: We provide reference ranges for lymphocyte proliferation responses to PHA from patients with CID and healthy controls.

scholarly journals T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Erik L. Clarke ◽  
A. Jesse Connell ◽  
Emmanuelle Six ◽  
Nadia A. Kadry ◽  
Arwa A. Abbas ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cell ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Cell Dynamics

Human equivalent of the mouse Nude/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 880-885 ◽  
Author(s):  
Claudio Pignata ◽  
Lucia Gaetaniello ◽  
Anna Maria Masci ◽  
Jorge Frank ◽  
Angela Christiano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Cd8 Cells ◽  
Tcr Repertoire ◽  
Immunologic Reconstitution

Abstract Human Nude/SCID (severe combined immunodeficiency) is the first severe combined immunodeficiency caused by mutation of the winged–helix–nude (WHN) gene, which is expressed in the thymus but not in the hematopoietic lineage. The disease is characterized by a T-cell defect, congenital alopecia, and nail dystrophy. A Nude/SCID patient who underwent bone marrow transplantation from the human leukocyte antigen–identical heterozygote brother was studied to investigate, in this unique model, the role of the thymus in immunologic reconstitution. Despite an increase in CD3+, CD4+, and CD8+cells, CD4+ CD45 RA naive lymphocytes were not regenerated. Conversely, naive CD8+ cells were normal. After an initial recovery, lymphocyte proliferation to mitogens progressively declined compared with controls and genotypically identical donor cells grown in the WHN+/−environment. Analysis of the T-cell receptor (TCR) repertoire of CD4+ cells revealed that only 3 of 18 Vβ families had an altered CDR3 heterogeneity length profile. Conversely, CD8+lymphocytes showed an abnormal distribution in most Vβ families. These data indicate that the thymus is differentially required in the reconstitution of CD4+ and CD8+ naive subsets and in the maintenance of their TCR repertoire complexity. Taken together, these findings suggest that bone marrow transplantation is ineffective in the long-term cure of this form of SCID.

IMMUNORECONSTITUTION IN SEVERE COMBINED IMMUNODEFICIENCY AFTER TRANSPLANTATION OF HLA-HAPLOIDENTICAL, T-CELL-DEPLETED BONE MARROW

The Lancet ◽  
1984 ◽  
Vol 323 (8380) ◽  
pp. 761-764 ◽  
Author(s):  
W. Friedrich ◽  
U. Vetter ◽  
B. Heymer ◽  
Y. Reisner ◽  
S.F. Goldmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency

scholarly journals Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25

Blood ◽  
2009 ◽  
Vol 113 (6) ◽  
pp. 1287-1293 ◽  
Author(s):  
Jing Chen ◽  
Meili Zhang ◽  
Wei Ju ◽  
Thomas A. Waldmann
Keyword(s):  
T Cell ◽  
Murine Model ◽  
Therapeutic Efficacy ◽  
Severe Combined Immunodeficiency ◽  
Control Group ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Antitumor Effects ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Abstract Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus I (HTLV-1) and is an aggressive malignancy of CD4, CD25-expressing leukemia, and lymphoma cells. There is no accepted curative therapy for ATL. Depsipeptide, a histone deacetylase inhibitor, has demonstrated major antitumor effects in leukemias and lymphomas. In this study, we investigated the therapeutic efficacy of depsipeptide alone and in combination with daclizumab (humanized anti-Tac) in a murine model of human ATL. The Met-1 ATL model was established by intraperitoneal injection of ex vivo leukemic cells into nonobese diabetic/severe combined immunodeficiency mice. Either depsipeptide, given at 0.5 mg/kg every other day for 2 weeks, or daclizumab, given at 100 μg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of soluble IL-2R-α (sIL-2R-α) and soluble β2-microglobulin (β2μ) (P < .001), and prolonged survival of the leukemia-bearing mice (P < .001) compared with the control group. Combination of depsipeptide with daclizumab enhanced the antitumor effect, as shown by both sIL-2R-α and β2μ levels and survival of the leukemia-bearing mice, compared with those in the depsipeptide or daclizumab alone groups (P < .001). The significantly improved therapeutic efficacy by combining depsipeptide with daclizumab supports a clinical trial of this combination in the treatment of ATL.

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