Sample Collection for Systems Evaluation of Patients With Unknown or Incompletely Characterized Immune Defects

Background:

The immune system defends the body against disease. It has many different parts spread out in

the body, including in the blood and skin. To learn more about it, researchers want to study samples from people with healthy immune systems and people with conditions that affect how the immune system works.

Objective:

To learn about how the different parts of the immune system come together to make a whole.

Eligibility:

People age 2 and older who have a condition that affects the immune system or have a family member with such a condition.

Design:

Participants will be screened with medical and medicine review. Other lab tests may also be reviewed. Some participants will take a pregnancy test.

Participants will give blood samples. They may also give saliva, stool, and urine samples.

A sterile cotton swab may be rubbed over their skin or inside the cheek or nose to collect cells.

If participants have samples collected as part of their regular medical care, their doctor may be asked to send parts of the samples that otherwise would be thrown away. These samples may be from biopsies, endoscopies, or other procedures.

Some participants may have optional skin punch biopsies. For this, their skin is numbed. Then a tool removes 1 or 2 small pieces of skin from the forearm or thigh.

Participants medical records will be checked to see if they have any changes in their health over time. If they have a study visit, they may talk about their medical history and have a physical exam.

Participation lasts 5 years....

Study Overview

• Status: Recruiting
• Conditions: Immunodeficiency

Detailed Description

Immunological disorders predispose affected individuals to a myriad of complications, including infection, immune dysregulation with autoimmune disease and aberrant inflammatory responses, and malignancy. Advances in genetic testing have propelled the discovery of the genetic underpinnings of numerous immunodeficiencies. However, a more complete picture of the immune system is needed to better characterize patients that present with the signs and symptoms of immunodeficiency or immune dysregulation in whom there is no identifiable genetic diagnosis. Many of our diagnostic tools, such as characterization of cell subset frequencies, look at only one parameter in the immune system, which is typically insufficient to capture the system s complexity. Systems immunology is a field of research aimed to identify and understand how the different components of the immune system work together in a coordinated manner to achieve its functions, such as protecting against pathogens and mounting effective responses after vaccination. The goal of this study is to collect patient samples to more deeply phenotype these individuals at the molecular and cellular levels using novel technologies in order to generate hypotheses regarding disease etiologies and mechanisms in subjects with an immune disorder without complete characterization or clear genetic etiology. We also aim to validate a specific observation seen in a previous study of patients with known monogenic immunological disorders. In the long-term, hypotheses generated in this study that address clinically significant, actionable questions will be pursued as separate investigations.

This hypothesis-generating sample collection study will recruit patients with unknown or incompletely characterized immune defects and their unaffected relatives. Under this protocol, samples will be collected at the NIH Clinical Center or mailed in for analysis using systems biology approaches to generate hypotheses regarding the potential etiologies and mechanisms of these immune defects. Initially, all subjects will give a blood sample and may give additional samples including saliva, stool, and skin punch biopsies. Subjects will be enrolled for 5 years and may be asked to give additional samples based on scientific need or changes in clinical status. Findings relevant to subjects health and medical care will be returned to them and referring healthcare providers.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Laura E Failla, C.R.N.P.; Phone Number: (240) 669-5323; Email: laura.failla@nih.gov
• Study Contact Backup: Name: Rachel D Sparks, M.D.; Phone Number: (240) 292-4642; Email: rachel.sparks@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY8664111010 800-411-1222; Email: prpl@cc.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study participants will be selected or referred to the protocol from other NIH groups whose patients have an uncharacterized immune defect. Unaffected biological relatives of these participants may also be recruited.

Description

• INCLUSION CRITERIA:

  1. Aged greater than or equal to 2 years.

  2. Meets 1 of the following criteria:

     a. Patient with a suspected or known/molecularly defined but incompletely characterized immune disorder (as determined by a referring NIH study staff member) AND meeting at least one of the following:

     i. within 1 year of screening, abnormal immune function demonstrated by at least one laboratory test result outside the normal range

     ii. history of severe or atypical infection, immune dysregulation (defined as autoimmunity, lymphoproliferation, or HLH), or autoinflammatory symptoms (defined as episodic fever often associated with dermatitis, gastrointestinal symptoms, and arthropathy).

     b. Biological unaffected relative of an individual meeting criterion 2a but who does not meet criterion 2a himself/herself. Unaffected relatives may be mother, father, siblings, children, grandparents, aunts, uncles, or first cousins to the individual.

  3. Willing to allow storage of samples and data for future research.
  4. For patients, currently or previously enrolled on an NIH protocol that performs WES or WGS and that allows sharing of sequence data.
  5. For unaffected relatives, able to provide informed consent.

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

1. History of secondary causes of immunodeficiency or dysregulation (e.g., HIV infection, immunodeficiency from chronic use of immunosuppressive or chemotherapeutic agents), at the discretion of the investigator.
2. Pregnancy.
3. Any condition that, in the opinion of the investigator, contraindicates participation in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with uncharacterized immune defects
Unaffected biological relatives

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CBC with differential, lymphocyte phenotyping, and whole blood RNA expression data analyzed in individuals with unknown or incompletely characterized immune defects.	CBC with differential, lymphocyte phenotyping, and whole blood RNA expression data analyzed in individuals with unknown or incompletely characterized immune defects.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CBC with differential and lymphocyte phenotyping in individuals with unknown or incompletely characterized immunological defects compared with age- and gender-matched healthy control	CBC with differential and lymphocyte phenotyping in individuals with unknown or incompletely characterized immunological defects compared with age- and gender-matched healthy control	Baseline

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Rachel D Sparks, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 4, 2023
• Last Verified: October 31, 2023

More Information

Terms related to this study

• Keywords: Natural History; Phenotype; Systems Immunology; Immunological Disorders; Monogenic; Hypothesis Generating
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes
• Other Study ID Numbers: 200084; 20-I-0084

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No