Protocol Details

Primary Immune Regulatory Disorders (PIRD): Longitudinal Study of Clinical Presentation, Treatment and Outcomes

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number	001752-I
Sponsoring Institute	National Institute of Allergy and Infectious Diseases (NIAID)
Recruitment Detail	Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 1 days Max Age: 99 Years
Referral Letter Required	Yes
Population Exclusion(s)	None
Keywords	Primary Immune Regulatory Disorders (PIRD); dysregulation symptoms
Recruitment Keyword(s)	None
Condition(s)	PIRD Disorders; Primary Immune Deficiency Disorder; Hematopoietic Stem Cell Transplant (HCT)
Investigational Drug(s)	None
Investigational Device(s)	None
Intervention(s)	None
Supporting Site	National Institute of Allergy and Infectious Diseases

Background:

Primary immune regulatory disorders (PIRD) are a group of rare diseases that affect how the immune system works. People with PIRD are at risk of inflammation and infections throughout their body. Researchers have found 129 gene changes that cause PIRD. But not everyone with these gene changes gets sick. Researchers want to understand why some people with PIRD genes do not get sick.

Objective:

To conduct a natural history study to compare people with PIRD with close relatives who have the same genes but no illness.

Eligibility:

People of any age with PIRD. Also, close relatives with the same gene changes but no illness.

Design:

All participants will fill out a questionnaire once a year for at least 5 years. They will answer questions about their general health, medical conditions, and treatments. The questionnaire takes about 20 minutes. Test results may be collected from the medical records of participants with PIRD. Adults may be asked about substance use and their quality of life.

Participants with PIRD may opt to provide blood and stool samples 2 times: once just after consenting to participate in the study, and once again about 1 year later.

Participants who will have a bone marrow transplant as part of their regular treatment for PIRD may opt to provide 2 extra sets of blood and stool samples; these will be collected before and after the transplant.

Healthy relatives will be asked to provide 1 blood sample. They will do this shortly after entering the study.

Eligibility

INCLUSION CRITERIA:

INCLUSION CRITERIA, LONGITUDINAL STUDY ARM

Individuals who meet the following criteria are eligible for enrollment as study participants:

1. Age between 0-99 years.

2. Must meet one of the following three Eligibility Categories:

a. Eligibility Category 1: 2 Major clinical criteria

b. Eligibility Category 2: 1 Major + 2 Minor clinical criteria

c. Eligibility Category 3: Either of the following

-1 Major clinical criterion + pathogenic or likely-pathogenic variant(s) in a PIRD-associated gene

-2 Minor clinical criteria + pathogenic or likely-pathogenic variant(s) in a PIRD-associated gene

Eligibility for the Study Arm must be documented and submitted for review by the PIRD Eligibility Review Panel and the PIRD Genetic Defects Review Panel.

All patients meeting enrollment criteria who were diagnosed after January 1, 1980 should be enrolled into the retrospective cohort whether living or deceased in order to avoid introducing bias.

INCLUSION CRITERIA, FAMILY MEMBER COHORT

Individuals who meet the following criteria are eligible for enrollment as study participants in the Family Member Cohort:

1. Age between 0-99 years.

2. Must be a first-degree relative (parent, sibling, or child) of a patient that meets Eligibility Category -AND- have the same pathogenic, PIRD-associated gene variant(s). *(Individuals carrying only one mutation in a PIRD-associated gene with a known autosomal-recessive pattern of inheritance will not be included).

3. Must not have clinical features that qualify them for enrollment on the Study Arm

Eligibility for the Family Member Cohort must be documented and submitted for review by the PIRD

Eligibility Review Panel and the PIRD Genetic Defects Review Panel.

EXCLUSION CRITERIA:

EXCLUSION CRITERIA, LONGITUDINAL STUDY ARM AND FAMILY MEMBER COHORT

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

1. Inability or unwillingness of a participant of family member to give written informed consent for enrollment in the prospective cohort or comply with study protocol.

2. Patients eligible for enrollment in other active PIDTC protocols (i.e. patients with classic or leaky SCID caused by absent RAG1/RAG2 function are eligible for enrollment in a PIDTC SCID protocol, but patients with hypomorphic RAG1/RAG2 function may primarily have immune dysregulation without significant immunodeficiency so are not eligible for enrollment on the PIDTC SCID protocol, but would be eligible for enrollment on this protocol).

3. Patients with genetic defects known to be associated with primary hemophagocytic lymphohistiocytosis (HLH) (other than XIAP or NLRC4).

4. Patients with documented HIV infection.

Citations:

Alam K, Maity A, Sinha SK, Rizopoulos D, Sattar A. Joint modeling of longitudinal continuous, longitudinal ordinal, and time-to-event outcomes. Lifetime Data Anal. 2021 Jan;27(1):64-90. doi: 10.1007/s10985-020-09511-3. Epub 2020 Nov 24. PMID: 33236257.

Chan AY, Leiding JW, Liu X, Logan BR, Burroughs LM, Allenspach EJ, Skoda-Smith S, Uzel G, Notarangelo LD, Slatter M, Gennery AR, Smith AR, Pai SY, Jordan MB, Marsh RA, Cowan MJ, Dvorak CC, Craddock JA, Prockop SE, Chandrakasan S, Kapoor N, Buckley RH, Parikh S, Chellapandian D, Oshrine BR, Bednarski JJ, Cooper MA, Shenoy S, Davila Saldana BJ, Forbes LR, Martinez C, Haddad E, Shyr DC, Chen K, Sullivan KE, Heimall J, Wright N, Bhatia M, Cuvelier GDE, Goldman FD, Meyts I, Miller HK, Seidel MG, Vander Lugt MT, Bacchetta R, Weinacht KG, Andolina JR, Caywood E, Chong H, de la Morena MT, Aquino VM, Shereck E, Walter JE, Dorsey MJ, Seroogy CM, Griffith LM, Kohn DB, Puck JM, Pulsipher MA, Torgerson TR. Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey. Front Immunol. 2020 Feb 21;11:239. doi: 10.3389/fimmu.2020.00239. PMID: 32153572; PMCID: PMC7046837.

Contacts: