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Study Description

Individuals, including infants who were identified by newborn screening, with a recent/new diagnosis of severe combined immune deficiency (SCID) may be eligible to be enrolled in the PIDTC research study: A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children with SCID Disorders. To determine eligibility for this study, potential participants (or, in the case of children, their parents/guardians) should consult with their doctors. The study follows participants with SCID prospectively. That is, the study enrolls participants who already have a plan to receive a blood and marrow transplant (BMT), enzyme therapy, or gene therapy in the future. After the procedure, participants are followed according to a study schedule. The participants' study visits will coincide with the follow-up visits with their doctors as part of their regular ongoing medical care. Participants with “leaky SCID”, reticular dysgenesis, and Omenn syndrome may also be eligible to participate in this study. As the PIDTC recognizes that there are many complex factors that go into the decision of which therapy (BMT, enzyme therapy, or gene therapy), the study does NOT dictate how the doctors should treat their patients. The decisions regarding therapy are made by the participants and their doctors. The study simply follows the participants' progress over time. This study does not involve experimental therapies.

A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children with SCID Disorders has been open since August 2010 and continues to be open and enrolling patients to the present day. The study plans to enroll approximately 540 patients with SCID. By studying new patients undergoing treatment for SCID, the goal is to learn more about: (1) outcomes from the treatment of SCID in the modern era of medicine, (2) what factors lead to the best long-term outcomes, such as best donor, conditioning regimen, timing of transplant, etc. and (3) what impact newborn screening and the early diagnosis of SCID has had on the long-term outcomes following BMT or gene therapy. A significant amount of information is also being gathered on how and when the immune system recovers after BMT, quality of life for long-term survivors, and about whether children develop normally after treatment.

A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children with SCID Disorders is the largest coordinated prospective study of patients with SCID ever performed. Information that we will learn, both now and in the future, will help doctors and other health professionals to better treat children with SCID. All hospitals within the PIDTC are enrolling patients with SCID for A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children with SCID Disorders study, ensuring that the outcomes are reflective of what happens in the “real world” as opposed to at just one or two large centers.

  • Study Weblinks:
  • Study Type:
    • Longitudinal
  • Number of study subjects that have individual-level data available through Authorized Access:
Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. The site also contains data dictionaries, variable summaries, documents, and truncated analyses, whenever available.

Study Inclusion/Exclusion Criteria

Patients who meet the following inclusion criteria and the intention is to treat with allogeneic hematopoietic cell transplant (HCT) are eligible for enrollment into Stratum A (Classic SCID) of the study:

  • Absence or very low number of T cells (CD3 T cells < 300/microliter), AND no or very low T cell function (< 10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) OR
  • T cells of maternal origin present

Note #1: When possible the proliferation to PHA should be calculated as a percentage of the lower limit of normal controls for that laboratory. If a range is not available, patients with stimulation index (SI) < 10 or whose absolute cpms are <10% of the cpms of the normal control of the day are eligible.
SI = (cpm of subject - cpm of medium) / cpm of medium
Note #2: For patients with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion.

Patients who meet the following criteria and the intention is to treat with HCT are eligible for enrollment into Stratum B (Omenn/Leaky SCID/Reticular Dysgenesis) of the study:

Leaky SCID

  • Maternal lymphocytes not detected,
  • AND either one or both of the following with rule-out of MHC Class I and II non-expression by flow cytometry (or histology):
    1. < 30% of lower limit of normal T cell function (as measured by response to PHA),
    2. Absent or less than 10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by flow/serology
  • AND either one or both of the following:
    1. > 80% of CD3+ or CD4 T cells are CD45RO+ (< 2 years of age)
    2. Genetic abnormality for SCID
  • AND does not meet criteria for Omenn Syndrome

Note: For patients with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion.

Omenn Syndrome (OS)

  • Generalized skin rash
  • Maternal lymphocytes not detected
  • IF: Maternal engraftment was not assessed and ruled out, the patient is not eligible as Omenn Syndrome.
  • > 80% of CD3 or CD4 T cells are CD45RO+ ( < 2 years of age)
  • Absent or low (< 30% lower limit of normal) T cell proliferation to antigens

IF: Proliferation to antigen was not performed, but at least 4 of the following 8 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the patient is eligible as Omenn Syndrome.

  1. Hepatomegaly
  2. Splenomegaly
  3. Lymphadenopathy
  4. Elevated IgE
  5. Elevated absolute eosinophil count
  6. *Oligoclonal T cells measured by CDR3 length or flow cytometry
  7. *Proliferation to PHA is reduced <30% of lower limit of normal or SI < 20
  8. *Mutation to SCID causing gene

Reticular Dysgenesis (RD)

  • < 300 / ul T cell number
  • None or < 10% lower limit of normal PHA proliferation
  • Severe neutropenia (< 200 / uL)
  • AND one or more of the following:
    1. Sensori-neural deafness OR
    2. Deficiency of marrow granulopoiesis OR
    3. A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.
    4. Note: Lack of response to short-term G-CSF administration can be used as a diagnostic criterion, however long term administration is not recommended

Patients who meet the following criteria and the intention is to treat with PEG-ADA ERT or gene therapy with autologous modified (gene transduced) cells are eligible for enrollment into Stratum C:

  • ADA Deficient SCID with intention to treat with PEG-ADA ERT
  • ADA Deficient SCID with intention to treat with gene therapy
  • X-linked SCID with intention to treat with gene therapy
  • Note: For patients with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion.

Patients who meet any one or more of the following exclusion criteria are disqualified from enrollment in Strata A, B, or C of the study.
Subjects will be excluded
as defined by:

  • Presence of an HIV infection (by PCR) or other cause of secondary immunodeficiency.
  • Presence of DiGeorge syndrome unless SCID genotype is also present.
  • Most patients with defects insuch as nucleoside phosphorylase, ZAP70, CD40 ligand, NEMO, XLP, RMP, DOCK8, MST1, ORAI1, STIM1, CORO1A MAGT1, IKBA, or RHOH will not meet the inclusion criteria for Stratum A, B, or C above. However, a patient with one of the above may meet the inclusion criteria for Stratum A or Stratum B and if so will be included.
    Version 3.0 28 August 2012
  • MHC Class I and MHC Class II antigen deficiency are specifically excluded.
  • Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency, transcobalamin deficiency.

Study History

  • Study Activated August 19, 2010
  • First Accrual September 2, 2010

Selected publications
Diseases/Traits Related to Study (MeSH terms)
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