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Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases

View Article: PubMed Central - PubMed

ABSTRACT

In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID) is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC) assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified) and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70) deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ) deficiency). As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID) patients were studied: 1 T-negative PID (cartilage-hair hypoplasia) and 4 T-positive PID (2 common immune deficiency (CID), 1 Wiskott–Aldrich syndrome, and 1 X-linked lymphoproliferative disease). Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982) were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.

No MeSH data available.


TREC distribution. TREC (panel A) and TREC/RNaseP ratio (panel B) distribution in the archived control samples.
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f0005: TREC distribution. TREC (panel A) and TREC/RNaseP ratio (panel B) distribution in the archived control samples.

Mentions: Satisfactory RNaseP amplification (above 4032 copies/μl of whole blood, according to the protocol by Gerstel-Thompson et al. [3]) was observed in all archived samples, thus no samples were excluded from the analysis. Distribution of TREC values and TREC/RNaseP ratio in the archived samples (known SCID/PID were excluded) are depicted in Fig. 1. A mean TREC value of 1162 ± 602 and mean RNaseP value of 42,439 ± 17,093 (in copies/μl blood) were determined in the archived samples. The mean ratio of TREC/RNaseP was 0.029 ± 0.015.


Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases
TREC distribution. TREC (panel A) and TREC/RNaseP ratio (panel B) distribution in the archived control samples.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121305&req=5

f0005: TREC distribution. TREC (panel A) and TREC/RNaseP ratio (panel B) distribution in the archived control samples.
Mentions: Satisfactory RNaseP amplification (above 4032 copies/μl of whole blood, according to the protocol by Gerstel-Thompson et al. [3]) was observed in all archived samples, thus no samples were excluded from the analysis. Distribution of TREC values and TREC/RNaseP ratio in the archived samples (known SCID/PID were excluded) are depicted in Fig. 1. A mean TREC value of 1162 ± 602 and mean RNaseP value of 42,439 ± 17,093 (in copies/μl blood) were determined in the archived samples. The mean ratio of TREC/RNaseP was 0.029 ± 0.015.

View Article: PubMed Central - PubMed

ABSTRACT

In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID) is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC) assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified) and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70) deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ) deficiency). As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID) patients were studied: 1 T-negative PID (cartilage-hair hypoplasia) and 4 T-positive PID (2 common immune deficiency (CID), 1 Wiskott–Aldrich syndrome, and 1 X-linked lymphoproliferative disease). Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982) were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.

No MeSH data available.