Mechanisms of Immune Deficiency

NCT03707782 | Unknown

• 1 other identifier: 18-0337
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.The purpose of this study is to learn more about the changes in genes, cells and proteins that cause immune deficiency diseases.
2. 2.The early stages of the study will focus on two groups of patients:
3. 3.members of families in which several persons have symptoms or medical histories that suggest immune deficiency.
4. 4.Patients who have received treatments with medications or drugs that affect functions of the immune system (secondary immune deficiencies).

Conditions

Immune Deficiency

Outcome Measures

Primary Outcomes (7)

• Measurement of Serum immune globulin

  The clinical definition of "hypogamma-globulinemia is values that are 2 SD below the mean value for the testing laboratory. For this study values that are below the lower limit of abnormal will be scored as abnormal. Chi-square analysis or Fisher's exact test will compare values between subjects with the wild type gene and the variant gene.

  each year for up to 20 years

• Antibody responses

  A four-fold difference or a post-immunization titer of ≥1.3 µg/ml is scored as a true antibody response. Antibody titers and avidity indices are transformed to log2 and evaluated using the Student's T-test.

  4 weeks

• Measurement of NK cell function

  Spearman correlation will be used to compare the relationship between expression of CD207a by NK cells that are activated with K562 cells or NK cells that are activated with PMA/iono.

  one time

• DNA sequencing

  When indicated, whole exome or whole genome sequencing will be done to identify genetic basis (if any) of the immune deficiency

  one time

• measurement of cellular components of the immune system

  Flow cytometry will be used to identify numbers of cells of various types (e.g.,subpopulations of B-cells and T-cells) to evaluate changes in various cell populations over time. This is especially important for studies of family members who carry disease-causing or disease-associated genes but are clinically health at the time of the first study

  each year for up to 20 years

• health outcome measurements

  The SF-36 form will be used serially to identify changes in health over time

  each year for up to 20 years

• Measurement of avidity

  avidity indices are transformed to log2 and evaluated using the Student's T-test

  each year for up to 20 years

Study Arms (2)

Individuals with immune deficiencies

aged 18 years or older and have an immune deficiency

Family members

aged 18 years or older and are related to a person who has an immune deficiency

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals aged 18 years or older and have an immune deficiency or are related to a person who has an immune deficiency.

You may qualify if:

• Immunodeficiency disease; or
• family member of individual with immunodeficiency disease

You may not qualify if:

• Persons with immune deficiencies that are secondary to other diseases such as malignancies.
• Persons who do not have immune deficiencies, persons who are not meet eligibility criteria

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Colorado Clinical & Translational Sciences Institute: collaborator

Study Sites (1)

UColorado

Denver, Colorado, 80045, United States

RECRUITING

Related Publications (5)

• Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B, Nelson RP Jr, Orange JS, Routes JM, Shearer WT, Sorensen RU, Verbsky JW, Bernstein DI, Blessing-Moore J, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller D, Spector SL, Tilles S, Wallace D; Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015 Nov;136(5):1186-205.e1-78. doi: 10.1016/j.jaci.2015.04.049. Epub 2015 Sep 12.

  PMID: 26371839 BACKGROUND

• O'Meara MM, Simon JA. Inner workings and regulatory inputs that control Polycomb repressive complex 2. Chromosoma. 2012 Jun;121(3):221-34. doi: 10.1007/s00412-012-0361-1. Epub 2012 Feb 19.

  PMID: 22349693 BACKGROUND

• Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT, Tarakhovsky A. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol. 2003 Feb;4(2):124-31. doi: 10.1038/ni876. Epub 2002 Dec 23.

  PMID: 12496962 BACKGROUND

• Caganova M, Carrisi C, Varano G, Mainoldi F, Zanardi F, Germain PL, George L, Alberghini F, Ferrarini L, Talukder AK, Ponzoni M, Testa G, Nojima T, Doglioni C, Kitamura D, Toellner KM, Su IH, Casola S. Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis. J Clin Invest. 2013 Dec;123(12):5009-22. doi: 10.1172/JCI70626. Epub 2013 Nov 8.

  PMID: 24200695 BACKGROUND

• Bodor C, Grossmann V, Popov N, Okosun J, O'Riain C, Tan K, Marzec J, Araf S, Wang J, Lee AM, Clear A, Montoto S, Matthews J, Iqbal S, Rajnai H, Rosenwald A, Ott G, Campo E, Rimsza LM, Smeland EB, Chan WC, Braziel RM, Staudt LM, Wright G, Lister TA, Elemento O, Hills R, Gribben JG, Chelala C, Matolcsy A, Kohlmann A, Haferlach T, Gascoyne RD, Fitzgibbon J. EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood. 2013 Oct 31;122(18):3165-8. doi: 10.1182/blood-2013-04-496893. Epub 2013 Sep 19.

  PMID: 24052547 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood lymphocytes, serum and plasma other tissue if availale

MeSH Terms

Conditions

Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Charles Kirkpatrick

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charles Kirkpatrick

CONTACT

(303) 724-7197; charles.kirkpatrick@ucdenver.edu

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 16, 2018
• Study Start: October 20, 2020
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 19, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)