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Defining Immunodeficiency in Heterotaxy Syndrome: Pilot Study Data

This study has been completed.
Litron Laboratories
Information provided by (Responsible Party):
Terence Prendiville, Children's Hospital Boston Identifier:
First received: August 23, 2013
Last updated: June 26, 2014
Last verified: June 2014

The investigators aim with this study is to investigate the mechanisms of immune deficiency in patients with heterotaxy syndrome through the use of novel biomarkers and a prospective questionnaire survey documenting the burden of infectious sequelae following enrollment. It is known that patients with under-active spleens (functional asplenia or hyposplenia) secondary to other (non-cardiac) conditions such as Sickle Cell Disease or Inflammatory Bowel Disease have a characteristic paucity of a B cell sub-class known as IgM memory B cell. This specific sub-class of B cell normally matures in the spleen and in those with an improperly functioning spleen a significant deficiency of this B cell class is seen on flow cytometry.

Similarly, these same patients are noted to have increased amounts of 'junk' DNA / nuclear remnant in their red cells. This is seen on microscopy as a dark particle inside the red cell and is termed a Howell Jolly Body (normally less than 2% of red cells have these dark particles present). Part of a functioning spleen's normal task is to rid the blood of red cells that contain nuclear remnants and an under-active spleen gets behind on this task with a build-up of Howell Jolly Bodies in red cells present in the bloodstream. Flow cytometry can very quickly and accurately quantify Howell Jolly Bodies as well as IgM memory B cells from a small (~1.5cc) sample of blood. Normal IgM memory B cell ranges are known for healthy children from infancy onwards allowing interpretation of results against normative data ranges.

The investigators aim to enroll 10 patients in this pilot study who have a diagnosis of heterotaxy syndrome (both asplenia and polysplenia) and to prospectively follow them after obtaining the initial biomarker sample. The family will be contacted once every two weeks for a period of 12 weeks and asked a series of simple questions taking approximately 5 minutes on any recent infectious sequelae or symptoms. The questions will elucidate history of minor illness such as low-grade fever or cough to more significant events such as admission for in-patient antibiotic therapy of bacterial sepsis. Ultimately, with this pilot study, the investigators hope to obtain sufficient data to support funding applications for a larger, multi-center trial that will allow us to develop biomarker thresholds for future risk of sepsis.

Heterotaxy Syndrome

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Defining Immunodeficiency in Heterotaxy Syndrome: Pilot Study Data

Resource links provided by NLM:

Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • Howell Jolly Body quantification [ Time Frame: At time of recruitment ] [ Designated as safety issue: No ]
  • IgM Memory B Cell quantification [ Time Frame: At time of recruitment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Results of phone questionnaire of parents documenting infectious symptoms and sequelae [ Time Frame: Once every 2 weeks for 12 weeks following enrollment ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: August 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Heterotaxy syndrome
Patients with a diagnosis of heterotaxy syndrome, as objectively defined by visceral heterotaxy (malrotation, interrupted inferior vena cava) with either documented polysplenia or asplenia by radiological imaging


Ages Eligible for Study:   up to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with a diagnosis of heterotaxy syndrome from inpatient and outpatient Cardiology settings at Boston Children's Hospital


Inclusion Criteria:

  • Diagnosis of heterotaxy syndrome, as objectively defined by visceral heterotaxy (malrotation, interrupted inferior vena cava) with either documented polysplenia or asplenia by radiological imaging.
  • 0-12 years old.

Exclusion Criteria:

  • Other known immunodeficiency or hyposplenic states (22q11, hypogammaglobulinemia, sickle hemoglobinopathy, liver cirrhosis or portal hypertension, organ transplantation, Fanconi syndrome, HIV or AIDS, chronic corticosteroid use, cancer, chemotherapy or other immunomodulating drug exposure, Addison's disease or pan-hypopituitarism, surgical splenectomy).
  • Red blood cell transfusion within the last 90 days as the donated red blood cells may interfere with calculation of the subject's Howell Jolly Body count. Patient enrollment will be deferred until 90 days has elapsed, assuming other eligibility requirements are met.
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Please refer to this study by its identifier: NCT01929967

United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Children's Hospital Boston
Litron Laboratories
Principal Investigator: Terence Prendiville, MB BCh BAO Children's Hospital Boston
  More Information

No publications provided

Responsible Party: Terence Prendiville, Pediatric Cardiology Fellow, Children's Hospital Boston Identifier: NCT01929967     History of Changes
Other Study ID Numbers: IRB-P00007001
Study First Received: August 23, 2013
Last Updated: June 26, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Boston:
Heterotaxy syndrome

Additional relevant MeSH terms:
Heterotaxy Syndrome
Immunologic Deficiency Syndromes
Abnormalities, Multiple
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Heart Defects, Congenital
Heart Diseases
Immune System Diseases
Lymphatic Diseases
Pathologic Processes
Splenic Diseases processed this record on November 27, 2014