scholarly journals Neonatal abstinence syndrome is a potential cause of low TREC copy number

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Adil Adatia ◽  
Ling Ling ◽  
Pranesh Chakraborty ◽  
Lauren Brick ◽  
Rae Brager
Keyword(s):  
T Cell ◽  
Copy Number ◽  
Cell Function ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Genetic Condition ◽  
T Cell Lymphopenia ◽  
Excision Circles

AbstractSevere combined immunodeficiency (SCID) is a rare genetic condition characterized by significant T cell lymphopenia and impaired T cell function. Many jurisdictions use the quantitation of T cell receptor excision circles (TRECs) to screen for SCID in newborns, but false positives may be seen in several conditions. We report 3 newborns with neonatal abstinence syndrome who presented with decreased TREC copy number.

A late preterm infant with lymphopenia

2020 ◽  
Vol 41 (2) ◽  
pp. 141-143 ◽  
Author(s):  
Shazia Lutfeali ◽  
David A. Khan ◽  
Christian Wysocki
Keyword(s):  
T Cell ◽  
Quantitative Polymerase Chain Reaction ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Unknown Etiology ◽  
Thymic Involution ◽  
Newborn Screen ◽  
T Cell Lymphopenia ◽  
Newborn Girl ◽  
Excision Circles

The newborn screen for severe combined immunodeficiency (SCID) uses real-time quantitative polymerase chain reaction for T-cell receptor excision circles and is highly sensitive for SCID. However, T-cell lymphopenia from other primary and secondary causes, such as DiGeorge syndrome, prematurity, thymic involution from stress, and thymectomy during cardiac surgery, is also detected. We present a newborn girl with T-cell lymphopenia of unknown etiology detected via abnormal newborn screen.

scholarly journals T-cell receptor and K-deleting recombination excision circles in newborn screening of T- and B-cell defects: review of the literature and future challenges

2013 ◽  
Vol 2 (1) ◽  
pp. 3 ◽  
Author(s):  
Marco Chiarini ◽  
Cinzia Zanotti ◽  
Federico Serana ◽  
Alessandra Sottini ◽  
Diego Bertoli ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
The United States ◽  
Combined Immunodeficiency ◽  
Blood Spots ◽  
T Cell Lymphopenia ◽  
Excision Circles

Since its introduction as a public health programme in the United States in the early 1960s, newborn blood screening (NBS) has evolved from the detection of phenylalanine levels on filter paper to the application of DNA-based technologies to identify T-cell lymphopenia in infants with severe combined immunodeficiency. This latter use of NBS has required the development of an assay for T-cell lymphopenia based on the quantification of T-cell receptor excision circles (TRECs) that could be performed on dried blood spots routinely collected from newborn infants. The TREC-based NBS was developed six years ago, and there have already been 7 successful pilot studies since then. Similarly, efforts are now being made to establish a screen for B-cell defects, in particular agammaglobulinaemia, taking advantage of the introduction of the method for the quantification of K-deleting recombination excision circles (KRECs). A further achievement of NBS could be the simultaneous recognition of T- and B-cell defects using the combined quantification of TRECs and KRECs from Guthrie card blood spots. This approach may help the early identification of infants with T- and B-cell deficiencies so that they can then be referred to specialised paediatric centres, where a precise diagnosis of severe combined immunodeficiency and agammaglobulinaemia can be performed, and where then they can immediately receive specific therapy. Simultaneous TREC and KREC quantification should also allow classification of patients into subgroups and help identify children with less serious primary immunodeficiencies. This would help avoid the opportunistic infections and frequent hospitalisations that result from a late or lack of diagnosis.

scholarly journals First Year of TREC-Based National SCID Screening in Sweden

2021 ◽  
Vol 7 (3) ◽  
pp. 59
Author(s):  
Christina Göngrich ◽  
Olov Ekwall ◽  
Mikael Sundin ◽  
Nicholas Brodszki ◽  
Anders Fasth ◽  
...  
Keyword(s):  
T Cell ◽  
Predictive Value ◽  
Screening Program ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Dried Blood Spots ◽  
First Year ◽  
Swedish Population ◽  
T Cell Lymphopenia ◽  
Excision Circles

Screening for severe combined immunodeficiency (SCID) was introduced into the Swedish newborn screening program in August 2019 and here we report the results of the first year. T cell receptor excision circles (TRECs), kappa-deleting element excision circles (KRECs), and actin beta (ACTB) levels were quantitated by multiplex qPCR from dried blood spots (DBS) of 115,786 newborns and children up to two years of age, as an approximation of the number of recently formed T and B cells and sample quality, respectively. Based on low TREC levels, 73 children were referred for clinical assessment which led to the diagnosis of T cell lymphopenia in 21 children. Of these, three were diagnosed with SCID. The screening performance for SCID as the outcome was sensitivity 100%, specificity 99.94%, positive predictive value (PPV) 4.11%, and negative predictive value (NPV) 100%. For the outcome T cell lymphopenia, PPV was 28.77%, and specificity was 99.95%. Based on the first year of screening, the incidence of SCID in the Swedish population was estimated to be 1:38,500 newborns.

Approach to primary immunodeficiency

2019 ◽  
Vol 40 (6) ◽  
pp. 465-469 ◽  
Author(s):  
Ashley L. Devonshire ◽  
Melanie Makhija
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Primary Immunodeficiency ◽  
Cell Receptor ◽  
Antibody Deficiency ◽  
Haemophilus Influenzae Type ◽  
Toll Like Receptor ◽  
T Cell Lymphopenia ◽  
Excision Circles

Primary immunodeficiency diseases are inherited defects of the innate or adaptive arms of the immune system that lead to an increase in the incidence, frequency, or severity of infections and/or immune dysregulation. There may be defects in the adaptive arm of the immune system, including combined immunodeficiencies and antibody deficiency syndromes, or abnormalities in innate immunity, such as defects of phagocytes, the complement pathway, or toll-like receptor mediated signaling. Recurrent sinopulmonary infections with encapsulated bacteria such as Haemophilus influenzae type B or Streptococcus pneumoniae may be characteristic of an antibody deficiency syndrome. Frequent viral, fungal, or protozoal infections may suggest T lymphocyte impairment. Multiple Staphylococcus skin infections and fungal infections may imply neutrophil dysfunction or the Hyper-IgE syndrome, and recurrent Neisseria infection is a characteristic manifestation of late complement component (C5‐9, or the membrane attack complex) defects. Recurrent viral or pyogenic bacterial infections, often without the presence of a significant inflammatory response, suggest a defect in toll-like receptor signaling. Mycobacterial infections are characteristic of defects in the interleukin (IL) 12/interferon γ pathway. Screening of newborns for T-cell lymphopenia by using polymerase chain reaction to amplify T-cell receptor excision circles, which are formed when a T cell rearranges the variable region of its receptor, serves as a surrogate for newly synthesized naive T cells. Because of very low numbers of T-cell receptor excision circles, severe combined immunodeficiency, 22q11.2 syndrome, and other causes of T-cell lymphopenia have been identified in newborns.

Neonatal Lymphopenia Screening Is Important For Early Diagnosis of Severe Combined Immunodeficiency

2021 ◽  
Author(s):  
Aykut Poyraz ◽  
Murat Cansever ◽  
Ipek Muderris ◽  
Turkan Patiroglu
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Umbilical Cord Blood ◽  
Lymphocyte Count ◽  
Blood Count ◽  
Complete Blood Count ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Combined Immunodeficiency ◽  
Excision Circles

Objective T-cell receptor excision circles are expensive for neonatal severe combined immunodeficiency screening in developing countries. We aimed to detect immunodeficiencies presenting with lymphopenia to enable screening in the general population and to improve awareness regarding lymphopenia among clinicians. Study Design This study was conducted prospectively. In all newborns included, complete blood count from umbilical cord blood samples was recorded. Absolute lymphopenia was defined as absolute lymphocyte count <3,000/mm3 in umbilical cord blood sample. Complete blood count was repeated at month 1 in cases found to have lymphopenia. Results Overall, 2,000 newborns were included in the study. Absolute lymphopenia was detected in 42 newborns (2.1%), while lymphocyte count was >3,000/mm3 in 1,958 newborns (97.9%). Two infants with persisted lymphopenia at the end of the first month; therefore, further evaluations such as lymphocyte subsets for severe combined immunodeficiency (SCID) were done. In the first infant, the lymphocyte subgroups were detected as compatible with T (−), B (−), natural killer cells (NK) (+) SCID phenotype RAG defect. Sanger sequencing revealed that NM_000448 c.2209C > T (p.R737C) homozygous mutation of RAG1 gene. In the other infant, the lymphocyte subgroups were found as considered with T (−), B (+) NK (−) SCID phenotype JAK3 defect. Both patients underwent hematopoietic stem cell transplantation from human leukocyte antigen-matched family member. Conclusion Absolute lymphopenia by complete blood count is a more simpler, relatively noninvasive and inexpensive screening methodfor detection of SCID in newborns compared with T-cell receptor excision circles technique. Key Points

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