Screening Protocol for Genetic Diseases of Lymphocyte Homeostasis and Programmed Cell Death

Primary Immune Deficiency Clinical Trial

Official title:

Screening Protocol for Genetic Diseases of Lymphocyte Homeostasis and Programmed Cell Death

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00246857
• Other study ID #: 060015
• Secondary ID: 06-I-0015
• Status: Recruiting
• Start date: February 12, 2007

Study information

• Verified date: February 22, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Michael J Lenardo, M.D.
• Phone: (301) 496-6754
• Email: mlenardo[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will determine the biochemical and genetic causes of inherited immune diseases affecting lymphocyte homeostasis. Lymphocytes are a type of white blood cell that fights infections. Normally, the body keeps a precise balance in which lymphocyte growth is matched by lymphocyte death. People with constantly enlarged lymph nodes or spleen, along with autoimmune disease, immunodeficiency, lymphoma, or other immune problems affecting lymphocytes may have an abnormality of the immune system in the cell growth and cell death processes that regulate lymphocyte homeostasis. Patients who have, or are suspected of having, an inherited lymphocyte homeostasis or programmed cell death susceptibility syndrome may be eligible for this study. Relatives of patients are also included. Participants' (patients and relatives) medical records are reviewed and blood samples are drawn for studies to identify genes involved in immune disorders. Tissues that have been removed from patients for medical reasons, such as biopsied tissues, may be examined for tissue and DNA studies. Relatives are studied to determine if some of them may have a very mild form of lymphocyte homeostasis disorder. Patients who have an immune problem that the researchers wish to study further will be invited to donate additional blood samples at irregular intervals (at least once a year) and to provide an update of their medical records at the same time. ...

Description:

This protocol is designed to screen patients with suspected or identified genetic diseases of immune cell homeostasis, reflecting abnormalities in programmed cell death, survival, development, activation, and/or proliferation. Patients determined by clinical history and initial outside evaluation by their referring physician to be of interest will be consented and enrolled into this study. Blood and other biological specimens from patients or their family members will be obtained for research studies related to understanding the genetic and biochemical bases of these diseases. Outside medical records will be obtained for chart review to correlate clinical history to research laboratory testing results. Results will be relayed to the referring physicians and, where applicable, patients will be referred to other relevant research studies at the NIH. The study will enroll up to 5000 patients and family members over the next 10 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 100 Years

Eligibility

• INCLUSION CRITERIA:

Patients known to have or suspected of having an inherited immune cell homeostasis, programmed cell death susceptibility syndrome, lymphocyte developmental block, or defective immune cell effector functions will be eligible for enrollment. We will enroll patients with suspected disease if the investigator agrees that there is a high index of suspicion. Blood relatives of enrolled patients will be eligible for enrollment. There will be no limit as to age, sex, race or disability. EXCLUSION CRITERIA: Severely debilitated health status or poor venous access may preclude obtaining adequate specimens for analysis. The minimum weight for infants on this protocol is 3 kg because of the limits of maximal acceptable blood draw volumes and minimum requirement for core laboratory tests would exceed the acceptable volume..

Related Conditions & MeSH terms

• Genetic Diseases, Inborn
• Immunologic Deficiency Syndromes
• Primary Immune Deficiency
• Primary Immunodeficiency Diseases

Locations

Country	Name	City	State
Turkey	Ankara Medical University	Ankara
Turkey	Gazi University	Ankara
Turkey	Hacettepe University	Ankara
Turkey	Marmara University	Istanbul
Turkey	Necemttin Erbakan University	Konya
United States	University of Michigan	Ann Arbor	Michigan
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Turkey, 

References & Publications (3)

Afzali B, Gronholm J, Vandrovcova J, O'Brien C, Sun HW, Vanderleyden I, Davis FP, Khoder A, Zhang Y, Hegazy AN, Villarino AV, Palmer IW, Kaufman J, Watts NR, Kazemian M, Kamenyeva O, Keith J, Sayed A, Kasperaviciute D, Mueller M, Hughes JD, Fuss IJ, Sadiyah MF, Montgomery-Recht K, McElwee J, Restifo NP, Strober W, Linterman MA, Wingfield PT, Uhlig HH, Roychoudhuri R, Aitman TJ, Kelleher P, Lenardo MJ, O'Shea JJ, Cooper N, Laurence ADJ. BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency. Nat Immunol. 2017 Jul;18(7):813-823. doi: 10.1038/ni.3753. Epub 2017 May 22. — View Citation

Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, Zhang Y, Liu Z, Fritz JM, Marsh R, Husami A, Kissell D, Nortman S, Chaturvedi V, Haines H, Young LR, Mo J, Filipovich AH, Bleesing JJ, Mustillo P, Stephens M, Rueda CM, Chougnet CA, Hoebe K, McElwee J, Hughes JD, Karakoc-Aydiner E, Matthews HF, Price S, Su HC, Rao VK, Lenardo MJ, Jordan MB. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015 Jul 24;349(6246):436-40. doi: 10.1126/science.aaa1663. — View Citation

Ozen A, Comrie WA, Ardy RC, Dominguez Conde C, Dalgic B, Beser OF, Morawski AR, Karakoc-Aydiner E, Tutar E, Baris S, Ozcay F, Serwas NK, Zhang Y, Matthews HF, Pittaluga S, Folio LR, Unlusoy Aksu A, McElwee JJ, Krolo A, Kiykim A, Baris Z, Gulsan M, Ogulur I, Snapper SB, Houwen RHJ, Leavis HL, Ertem D, Kain R, Sari S, Erkan T, Su HC, Boztug K, Lenardo MJ. CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med. 2017 Jul 6;377(1):52-61. doi: 10.1056/NEJMoa1615887. Epub 2017 Jun 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	determination of underlying susceptibility trait(s) and elucidation of its mechanism of action	Goal of this study is to determine the molecular, genetic, biochemical basis for an immune problem.	2030

External Links

•   NIH Clinical Center Detailed Web Page