Clinical trial NCT03707782: Mechanisms of Immune Deficiency
Official title: Mechanisms of Immune Deficiency
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Immune Deficiency
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Colorado Clinical & Translational Sciences Institute
First posted: 2018-10-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
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.

Brief summary: 1. The purpose of this study is to learn more about the changes in genes, cells and proteins that cause immune deficiency diseases.
2. The early stages of the study will focus on two groups of patients:

   1. members of families in which several persons have symptoms or medical histories that suggest immune deficiency.
   2. Patients who have received treatments with medications or drugs that affect functions of the immune system (secondary immune deficiencies).

It is hoped that studies will provide guidelines for extension of the research to other patient groups. Up to 200 patients and family members will be invited to participate.

Detailed description: The experiments that are proposed in this portion of the study are intended to:

1. characterize the significance of the variant form of EZH2 identified in this family. They will characterize the degree of methylation of lysine 27 of histone H3 in subjects with the variant and members of the same family who have the wild type gene. The functional methyltransferase activity of the variant and wild type genes will be measured.
2. characterize the current status of B-cell maturation and function in subjects with either the variant gene and the wild type gene.
3. characterize B-cell function (antibody production) and the quality of antibody produced after immunizations in subjects with the wild type gene or the variant gene.

Eligibility criteria: Inclusion Criteria:

1. Immunodeficiency disease; or
2. family member of individual with immunodeficiency disease

Exclusion Criteria:

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

Primary outcomes:
measure: Measurement of Serum immune globulin
timeFrame: each year for up to 20 years
measure: Antibody responses
timeFrame: 4 weeks
measure: Measurement of NK cell function
timeFrame: one time
measure: DNA sequencing
timeFrame: one time
measure: measurement of cellular components of the immune system
timeFrame: each year for up to 20 years
measure: health outcome measurements
timeFrame: each year for up to 20 years
measure: Measurement of avidity
timeFrame: each year for up to 20 years
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: UColorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Charles Kirkpatrick
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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.