Screeningsprotokol for genetiske sygdomme i lymfocythomeostase og programmeret celledød
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.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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 may be referred to other relevant research studies at the NIH.
The study will enroll up to 5000 patients and family members over the next 20 years.
Undersøgelsestype
Tilmelding (Anslået)
Kontakter og lokationer
Studiekontakt
- Navn: Helen C Su, M.D.
- Telefonnummer: (301) 451-8783
- E-mail: hsu@mail.nih.gov
Studiesteder
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Maryland
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Bethesda, Maryland, Forenede Stater, 20892
- Rekruttering
- National Institutes of Health Clinical Center
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Kontakt:
- For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
- Telefonnummer: TTY dial 711 800-411-1222
- E-mail: ccopr@nih.gov
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109-0624
- Rekruttering
- University of Michigan
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Kontakt:
- Kelly Walkovich, M.D.
- Telefonnummer: 215-590-2204
- E-mail: kwalkovi@med.umich.edu
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Taipei, Taiwan, Taiwan 100
- Rekruttering
- National Taiwan University
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Kontakt:
- Aris Cheng
- E-mail: aristine@hotmail.com
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Ankara, Tyrkiet (Türkiye)
- Rekruttering
- Ankara Medical University
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Kontakt:
- Aydan Ikinciogullari, MD
- Telefonnummer: 903123191440 Not Listed
- E-mail: aydan@mac.com
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Ankara, Tyrkiet (Türkiye)
- Rekruttering
- Gazi University
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Kontakt:
- Sinan Sari, MD
- Telefonnummer: (031) 220-2414
- E-mail: drsinansari@gmail.com
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Ankara, Tyrkiet (Türkiye)
- Rekruttering
- Hacettepe University
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Kontakt:
- Deniz Cagdaz
- Telefonnummer: +903123051080
- E-mail: dcagdas@gmail.com
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Istanbul, Tyrkiet (Türkiye)
- Rekruttering
- Marmara University
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Kontakt:
- Ahmet Ozen, M.D.
- Telefonnummer: +90216625454
- E-mail: ahmetozen_md@yahoo.com
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Istanbul, Tyrkiet (Türkiye)
- Rekruttering
- Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital
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Konya, Tyrkiet (Türkiye)
- Rekruttering
- Necemttin Erbakan University
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Kontakt:
- Sevgi Keles, M.D.
- Telefonnummer: Not Listed
- E-mail: sevgi_keles@yahoo.com
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Patients referred by physician with a suspected inherited immune deficiency and their unaffected relatives.
Beskrivelse
- 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.
Co-enrollment guidelines: Participants may be co-enrolled in other studies including NIH protocols 05-I-0213, 93-I-0063 and 17-I-0122. Participants should inform the investigator of participation in other research studies.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: OTHER
- Tidsperspektiver: PROSPECTIVE
Kohorter og interventioner
Gruppe / kohorte |
|---|
|
patients referred by physician with a suspected inherited immune deficiency
patients referred by physician with a suspected inherited immune deficiency |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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determination of underlying susceptibility trait(s) and elucidation of its mechanism of action
Tidsramme: 2030
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Goal of this study is to determine the molecular, genetic, biochemical basis for an immune problem. |
2030
|
Samarbejdspartnere og efterforskere
Efterforskere
- Ledende efterforsker: Helen C Su, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Publikationer og nyttige links
Generelle publikationer
- 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.
- 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.
- 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.
- Comrie WA, Faruqi AJ, Price S, Zhang Y, Rao VK, Su HC, Lenardo MJ. RELA haploinsufficiency in CD4 lymphoproliferative disease with autoimmune cytopenias. J Allergy Clin Immunol. 2018 Apr;141(4):1507-1510.e8. doi: 10.1016/j.jaci.2017.11.036. Epub 2018 Jan 2. No abstract available.
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Anslået)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 060015
- 06-I-0015
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
If an individual requests to have their raw sequencing data, we have asked the IRB for permission. This has happened in one case. @@@@@@@@@@@@In another case during this reporting period, a subject asked us to share raw sequencing data with an academic center for analysis. This required a DTA which was recently completed.@@@@@@@@@@@@Sequencing is done under research conditions and is not shared with a subject unless it is verified with a repeat independent sample and CLIA certified.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
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