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6906: Primary Immune Regulatory Disorders (PIRD): Longitudinal Study of Clinical Presentation, Treatment and Outcomes


Primary Immune Regulatory Disorders (PIRD) are a diverse group of rare genetic conditions in which the immune system does not respond appropriately to challenges or is not appropriately regulated in its responses. These changes can lead to underactive or overactive immune function. This is called immune dysregulation. Multiple organ systems can be affected. These disorders can be caused by autoimmunity (a mistaken attack on healthy tissues or organs by the immune system), excessive inflammation (an overactive defense reaction by the immune system), and non-malignant lymphoproliferation (an abnormal increase in lymphocytes, a type of white blood cell). PIRD patients can be treated with different types of immune suppressive medications, and some are treated with a bone marrow transplant. Currently, there is limited data on what is the ideal treatment for treating PIRD patients.

About this Study

This study focuses on the natural history of patients with PIRD to help collect data on ideal therapies for these patients. There are two groups that are being studied. The first group enrolls patients who have clinical symptoms commonly seen in PIRD. These patients can have a known or unknown genetic defect. We will collect retrospective data from the medical chart and follow these patients over time prospectively. This study will help characterize the clinical symptoms and responses to treatments both medications and bone marrow transplant. The study will collect data yearly from the clinical record. There will also be research samples at the start of enrollment and one year later. If the patient receives a bone marrow transplant, research samples will be collected one month prior to transplant and a year later.

The second group is focused on family members of PIRD patients enrolled in the first group with a known genetic mutation. These family members will have the same genetic change but do not have clinical symptoms of PIRD. These participates will answer yearly questionnaires to monitor of symptoms.

Targeted Enrollment

Participants considered eligible to participate in the PIRD patient group include the following:

  • Males or females between the ages of 0-99 years old
  • Have some combination of the following clinical symptoms:
    • Immune-mediated gastrointestinal disease (eg inflammatory bowel disease, autoimmune enteropathy)
    • Lung disease that is not due to infection or asthma
    • Autoimmune blood diseases (eg autoimmune hemolytic anemia, autoimmune thrombocytopenia, autoimmune neutropenia)
    • Lymphoproliferation that is not from cancer (ie multiple enlarged lymph nodes and spleen)
    • Autoimmune endocrine disease (eg Type I Diabetes, Hashimoto’s Thyroiditis)
    • Immune-mediated liver disease not from infection or medication
    • Immune-mediated skin disease (eg eczema, psoriasis, etc.)
    • Rheumatologic disease (eg types of arthritis, myositis, vasculitis)
    • Low IgG levels not from gut or kidney loss and requiring IgG replacement
    • Onset of immune-mediated disease <5yo
  • May have a known PIRD gene mutation (eg ADAM17,, BACH2, CARD11, CD3G, CTLA4, DEF6, DOCK8, ERBIN, FOXP3, ICOS, IKBKG, IKZF1, IL10, IL10RA, IL10RB, IL21R, IL2RA, IRF2BP2, ITCH, JAK1, LRBA, MVK, NFAT5, NFKB1, NFKB2, NFKBIA, OTULIN, PIK3CD, PIK3R1, PRKCD, PSTPIP1, PTEN, RAG1, RAG2, RELA, STAT1, STAT3, STAT5B, TNFAIP3, WAS, WIP, XIAP). Newly described PIRD genes may also be included during this study.

Participants eligible to participate in the family member group have the following:

  • Parents or siblings of a PIRD patient enrolled in the study
  • Have the same genetic change as the PIRD patient
  • Do not have clinical symptoms that meet the criteria for the PIRD patient group

You are not eligible to participate if:

  • Eligible for another Primary Immune Deficiency Treatment Consortium (PIDTC) protocol
  • Have a known gene defect causing primary hemophagocytic lymphohistiocytosis (HLH)
  • Have documented HIV infection