Neonatal Screening of Severe Combined Immunodeficiencies

Severe Combined Immunodeficiency Clinical Trial

Official title:

Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02590328
• Other study ID #: NSSCID
• Status: Completed
• Start date: December 2015
• Est. completion date: December 2021

Study information

• Verified date: January 2021
• Source: Children's Hospital of Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of the proposed research is to observe the prevalence and establish the validity of a newborn screening method for severe combined immunodeficiency (SCID). The assay to be used is developed on the basis of PCR quantification of T-cell receptor excision circles (TRECs) that is absent in SCID patients, thus correlating with the disease.

Description:

Severe combined Immunodeficiencies (SCID) are a group of inherited diseases of the immune system by characterized profound abnormalities of B and T cell development. Infants with SCID require prompt clinical response to prevent life threatening infection and studies show significantly improved survival in babies Diagnosed at birth as a result of previous family history. SCID follows criteria for population based newborn screening since it is asymptomatic at birth and fatal within the first year of life, the confirmation of the disease is easy, there is a curative treatment, and it is known that early stem cell transplantation improves survival.To show that early diagnosis of SCID with a TREC screening assay can warrant timely treatment of the disease and avoid life-threatening infections on patients. Babies with SCID are unable to fight infections. They become severely ill in their first months of life and do not survive unless their immune systems can be restored. SCID can be treated by bone marrow transplant if recognized early. We undertake the task of newborn screening in the whole region of Shanghai, So the newborn screening test to be employed in this study is designed to diagnose SCID before infections occur. Through this study, we hope to confirm the prevalence of SCID in China and the benefits of newborn screening for early diagnosis of SCID.

Quantification of TRECs (T-cell receptor excision circles) in DNA extracted from Guthrie samples is a sensitive screening test for Specific and SCID. TRECs are small-circle DNA molecules which are by-products of T cell maturation in the thymus, and their numbers reflect the number of recently emigrated T-cells from the thymus. Since all infants with SCID have a profound decrease in T-lymphocytes no matter what gene mutations are involved, logically the number of TRECs present in blood collected via dried blood spots 1-2 days post delivery on SCID babies should be very low when compared with healthy newborns. The TREC assay includes DNA extraction from a 3 mm punch of dried blood specimen in a 96-well plate format. The extracted DNA undergoes Real-time qPCR procedure on 7900 HT Fast Real-time PCR System (ABI). The TREC copy number is calculated relative to a standard curve generated from serially diluted plasmids which contain a known number of TREC. The investigators propose in this study to perform a neonatal screening of SCID, in a population of 200,000 babies over a period of three years. The investigators propose to study the incidence of SCID, mortality & rate of disability, clinical utility and SCID screening to demonstrate that could result in a broad benefit to individuals detected, making screening relatively efforts in spite of the low incidence of the disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180000
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 28 Days

Eligibility

Inclusion Criteria:

1. No more than 28 days old

2. Newborns who was born in Shanghai and in 2016 to 2020

3. Blood sample card was collected in 72 hours after birth

Exclusion Criteria:

1. Lack of parental consent

2. Sample card was damaged

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Neonatal Screening
• Severe Combined Immunodeficiency

Locations

Country	Name	City	State
China	Children's Hospital of Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Fudan University

Country where clinical trial is conducted

China, 

References & Publications (8)

Burroughs L, Woolfrey A. Hematopoietic cell transplantation for treatment of primary immune deficiencies. Cell Ther Transplant. 2010 Aug 31;2(8). doi: 10.3205/ctt-2010-en-000077.01. — View Citation

de Pagter AP, Bredius RG, Kuijpers TW, Tramper J, van der Burg M, van Montfrans J, Driessen GJ; Dutch Working Party for Immunodeficiencies. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening. Eur J Pediatr. 2015 Sep;174(9):1183-8. doi: 10.1007/s00431-015-2518-4. Epub 2015 Apr 1. — View Citation

de Silva R, Gunasena S, Ratnayake D, Wickremesinghe GD, Kumarasiri CD, Pushpakumara BA, Deshpande J, Kahn AL, Sutter RW. Prevalence of prolonged and chronic poliovirus excretion among persons with primary immune deficiency disorders in Sri Lanka. Vaccine. 2012 Dec 14;30(52):7561-5. doi: 10.1016/j.vaccine.2012.10.035. Epub 2012 Oct 22. — View Citation

Kobrynski L. Newborn screening for severe combined immune deficiency (technical and political aspects). Curr Opin Allergy Clin Immunol. 2015 Dec;15(6):539-46. doi: 10.1097/ACI.0000000000000221. Review. — View Citation

Puck JM, Routes J, Filipovich AH, Sullivan K. Expert commentary: practical issues in newborn screening for severe combined immune deficiency (SCID). J Clin Immunol. 2012 Feb;32(1):36-8. doi: 10.1007/s10875-011-9598-3. Epub 2011 Oct 20. — View Citation

Puck JM. Neonatal screening for severe combined immune deficiency. Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):522-7. Review. — View Citation

Puck JM; SCID Newborn Screening Working Group. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. 2007 Oct;120(4):760-8. — View Citation

Rozmus J, Junker A, Thibodeau ML, Grenier D, Turvey SE, Yacoub W, Embree J, Haddad E, Langley JM, Ramsingh RM, Singh VA, Long R, Schultz KR. Severe combined immunodeficiency (SCID) in Canadian children: a national surveillance study. J Clin Immunol. 2013 Nov;33(8):1310-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	prevalence of SCID		At 28 days after birth
Secondary	Number of detected SCID patients		At 28 days after birth