Oral Bacteria and Immune System Problems Involved in Gum Disease (Periodontitis)

This protocol is a cross sectional study designed to investigate the clinical, microbiologic,
and immunologic consequences of immune dysfunction (particularly dysfunction due to primary
immune defects) in the oral cavity. The hypothesis is that systemic immune dysfunction,
attributed to monogenic immune defects in most of our populations of interest, will lead to
alterations in the local immune response and microbial colonization and ultimately predispose
to susceptibility to oral infections and inflammatory conditions. Of particular interest to
this protocol is the susceptibility of select patient populations with immune dysfunction to
periodontal disease. Whereas patients with hyper-immunoglobulin E syndrome (HIES) are an
important focus of this research, enrollment will be open to a broader population, including
monogenic immune defects such as leukocyte adhesion deficiency-1 (LAD-1), chronic
granulomatous disease (CGD), as well as patients with defects in cytokine signaling.

For inclusion in this study, ID subjects must have a current diagnosis of a primary immune
defect, and be enrolled in an NIH protocol that is following their medical issues and through
which they are required to get a dental consult. Data from the dental consult, collected
under the parent protocol, will be analyzed through this protocol to assess the type and
extent of oral manifestation in patients with these immune defects. In addition to the
information collected as part of the consult, subjects will undergo sampling for oral fluids,
microbes, and blood sampling. Each patient subject 18 years of age or older will also undergo
an oral biopsy. Systemically healthy volunteer subjects will be screened and classified as
with/without periodontitis. Healthy volunteers will be clinically evaluated and enrolled for
a single visit, at which they will undergo oral fluid/microbe/tissue/blood sampling/oral
biopsy for research purposes.

The primary aim of this protocol is to use modern methodologies to characterize the immune
response and microbial colonization in the oral cavity in health and patients with primary
immune defects. By particularly studying subjects with monogenic immune defects, we aim to
increase the understanding of the role of specific immune molecules and pathways in the
balance of host/microbial interactions on mucosal surfaces such as the oral cavity.

- INCLUSION CRITERIA:

Patients with Immune Dysfunction:

-Patients with an established monogenic immune defect will be eligible for screening
inclusion under this protocol.

- Diagnosis of monogenic immune defect

- Greater than or equal to 7 years old

- Be concurrently enrolled in a protocol at NIH that is following the medical condition
of the patient and under which a dental consult was requested

- Willing to allow genetic testing

Healthy Volunteer Subjects:

- In good general health

- Greater than or equal to 18 years old

- Willing to allow genetic testing

- Have a minimum of 20 natural teeth

Healthy Volunteer Subjects with Severe Periodontitis 3.2.3 (treatment group) additional
criteria:

- Active untreated disease (visible signs of tissue inflammation including
erythema/edema, generalized bleeding upon probing)

- Periodontal disease defined as generalized measured bone loss of >5mm as measured on
periodontal exam.

EXCLUSION CRITERIA:

All Subjects:

- History of Hepatitis B or C

- History of HIV

- Prior radiation therapy to the head or neck

- Have an active malignancy except localized basal or squamous cell carcinoma of the
skin

- Have been treated with systemic chemotherapeutics or radiation therapy within 5 years
of screening

- Pregnant or lactating

- If participation in the protocol would not be safe or in the subject s best interest
in the opinion of either the PI or the primary medical team.

Additional Exclusions for Healthy Volunteers:

- Diagnosis of diabetes and/or HbA1C level >6%

- More than 3 hospitalizations in the last 3years

- Have an autoimmune disorder such as Lupus, Rheumatoid arthritis, etc.

- In the 3 months before study enrollment, have used any of the following:

- Systemic (intravenous, intramuscular, or oral) antibiotics

- Oral, intravenous, intramuscular, intranasal, or inhaled corticosteroids or other
immunosuppressants (e.g., cyclosporine)

- Cytokine therapy

- Methotrexate or immunosuppressive chemotherapeutic agents

- Large doses of commercial probiotics (greater than or equal to 10(8)
colony-forming units or organisms per day); includes tablets, capsules, lozenges,
chewing gum, or powders in which a probiotic is a primary component; ordinary
dietary components such as fermented beverages/milks, yogurts, and foods do not
apply

- Have used tobacco products (including e-cigarettes) within 1 year of screening

- Unwillingness to consent to oral biopsy

- NIH employees working in the Oral Immunity and Inflammation Unit and members of the
Clinical Research Core Team will not be eligible for enrollment.

Additional Exclusions for Healthy Volunteers with Periodontal Disease:

- Mild/moderate non-active disease (absence of active inflammatory lesions)

- Subjects with urgent/complex restorative needs (ex. severe active carious
lesions/fractured dentition)

- Subjects in need for advance periodontal care (including bone/tissue grafts/implants)