Detection and Characterization of Host Defense Defects

NCT ID: NCT00001355

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 3600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1993-09-01

Brief Summary

This protocol is designed to evaluate selected patients with documented recurrent or unusual infections and their family members for clinical and laboratory correlates of immune abnormalities. It allows long term follow up of patients with host defense defects and permits the periodic study of their blood, urine, saliva, skin, stool and vaginal specimens or wound drainage from such patients or their family members for medically indicated purposes and research studies related to understanding the genetic and biochemical bases of these diseases. This protocol may help provide patients and materials for the development of therapies for these diseases.

This study will:

1. Determine the biochemical and genetic causes of inherited immune diseases affecting phagocytes (white blood cells that defend against bacterial and fungal infections)

2. Try to develop better ways to diagnose and treat patients with these diseases, and to prevent, diagnose and treat their infections

Patients and family members may undergo the following procedures:

• A personal and family medical history, physical examination and other procedures, which may include various blood tests; urinalysis; saliva collection; imaging studies such as chest X-ray, computed tomography (CT) or magnetic resonance imaging (MRI); and lung function studies, dental examination or eye examinations, if medically indicated.
• Patients who have draining wounds will have fluid collected from these wounds for biochemical study.
• Tissues removed as part of medical care, such as pieces of lung, liver, or teeth, or biopsies of these tissues will be studied.
• Patients who have an immune problem that investigators wish to study further will be asked to return to NIH for follow-up visits at irregular intervals, but at least every 6 months. The visits will include an updated medical history, examination directed at the particular medical problem related to the immune disorder, follow-up of abnormal tests or treatment, and collection of blood, saliva, urine, or wound fluid for study.
• Patients may have genetic testing and must be willing to have specimens stored for future research.
• Family members will have a medical history, saliva or urine collection, and chest X-ray or other imaging study, if medically indicated.
• Normal volunteers who have had tissue biopsies or pieces of tissue removed as part of medical care, such as pieces of lung, liver, or teeth, will have these tissues studied.
• NIH does not cover the cost of the initial screening visit for travel or lodging. A financial assessment may determine if the patient is eligible for financial assistance. This study does not enroll children under the age of 2.
• Patients will be asked to obtain their medical records, previous test results, or imaging studies prior to the first visit.

Detailed Description

This protocol is designed to evaluate selected patients with documented recurrent or unusual infections and their family members for clinical and in vitro correlates of immune abnormalities. It will also allow long term follow up of patients with host defense defects and permit us to periodically obtain blood, urine, saliva, skin, other excess biopsy tissue, breast milk, stool and vaginal specimens or wound drainage from such patients or their family members for medically indicated purposes and research studies related to understanding the genetic and biochemical bases of these diseases. This protocol may help provide patients and materials for the development of therapies for these diseases in the future.

Conditions

Immune Defects

Keywords

Immune Deficiency; Infection; Phagocytes; Cytokines; Genetics; Natural History

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy Volunteer

Healthy Volunteer to serve as controls

No interventions assigned to this group

Patient

Patients known to have or suspected of having an immune defect significantly or primarily involving the phagocytes

No interventions assigned to this group

Patient Relatives

blood relatives of patients

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Patients known to have or suspected of having an immune defect significantly or primarily involving the phagocytes will be eligible for enrollment, as well as their blood relatives. Such syndromes include but are not limited to those listed above. Eligibility will not be limited based on sex, race, or disability. Patients or patient relatives must be over 1 month of age.

The patient and patient relative cohorts will include the following special populations:

• Children: Children are included in this study because immune defects may present in early childhood, and early diagnosis or characterization may benefit subjects.
• Decisionally impaired adults: Patients and patient relatives will be able to provide informed consent for themselves or if they lack the capacity to provide informed consent, the study team will obtain consent from the legally authorized representative. Patients with underlying immune disorders, autoimmune phenomena or severe infections may sometimes present with delirium, encephalopathy, or coma and are therefore unable to provide informed consent. Excluding patients who are unable to provide consent could adversely impact patient access to medical therapy at the NIH as well as adversely impact research recruitment. Excluding patients unable to provide consent would also essentially prohibit us from evaluating patients at higher risk for adverse outcomes and therefore skew our understanding of disease. Similarly, enrolled patient subjects who lose the ability to provide ongoing consent during study participation may continue in the study. The risks and benefits of participation for subjects unable to consent should be identical to those described for less vulnerable patients. The process for obtaining consent for these individuals is described below.

Healthy volunteers will be healthy adults between the age of 18 and 80 years of either sex, and they must be able to provide informed consents for themselves.

Exclusion Criteria

The presence of an acquired abnormality which leads to immune defects, such as HIV, cytotoxic chemotherapy or malignancy, could be grounds for possible exclusion if, in the opinion of the investigator, the presence of such disease process interfered with evaluation.

Individuals with dementia that impairs obtaining informed consent are excluded from enrolling as healthy volunteers, although such subjects may enroll in the patient or relative cohorts if consent can be obtained as described below.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: collaborator

University of South Florida

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven M Holland, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

France; United States

Central Contacts

Dawn E Shaw, R.N.

Role: CONTACT

Phone: (301) 401-4740

Email: dawn.shaw2@nih.gov

Steven M Holland, M.D.

Role: CONTACT

Phone: (301) 402-7684

Email: sholland@mail.nih.gov

References

Donko A, Sharapova SO, Kabat J, Ganesan S, Hauck FH, Bergerson JRE, Marois L, Abbott J, Moshous D, Williams KW, Campbell N, Martin PL, Lagresle-Peyrou C, Trojan T, Kuzmenko NB, Deordieva EA, Raykina EV, Abers MS, Abolhassani H, Barlogis V, Milla C, Hall G, Mousallem T, Church J, Kapoor N, Cros G, Chapdelaine H, Franco-Jarava C, Lopez-Lerma I, Miano M, Leiding JW, Klein C, Stasia MJ, Fischer A, Hsiao KC, Martelius T, Seppanen MRJ, Barmettler S, Walter J, Masmas TN, Mukhina AA, Falcone EL, Kracker S, Shcherbina A, Holland SM, Leto TL, Hsu AP. Clinical and functional spectrum of RAC2-related immunodeficiency. Blood. 2024 Apr 11;143(15):1476-1487. doi: 10.1182/blood.2023022098.

Reference Type: DERIVED

PMID: 38194689 (View on PubMed)

Schindler MK, Pittaluga S, Enose-Akahata Y, Su HC, Rao VK, Rump A, Jacobson S, Cortese I, Reich DS, Uzel G. Haploinsufficiency of immune checkpoint receptor CTLA4 induces a distinct neuroinflammatory disorder. J Clin Invest. 2020 Oct 1;130(10):5551-5561. doi: 10.1172/JCI135947.

Reference Type: DERIVED

PMID: 32955488 (View on PubMed)

Burbelo PD, Browne SK, Sampaio EP, Giaccone G, Zaman R, Kristosturyan E, Rajan A, Ding L, Ching KH, Berman A, Oliveira JB, Hsu AP, Klimavicz CM, Iadarola MJ, Holland SM. Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia. Blood. 2010 Dec 2;116(23):4848-58. doi: 10.1182/blood-2010-05-286161. Epub 2010 Aug 17.

Reference Type: DERIVED

PMID: 20716769 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_1993-I-0119.html

NIH Clinical Center Detailed Web Page

Other Identifiers

93-I-0119

Identifier Type: -

Identifier Source: secondary_id

930119

Identifier Type: -

Identifier Source: org_study_id