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

* INCLUSION CRITERIA:

Subjects with Genetic Immune Defects:

Patients with a known genetic immune defect will be eligible for screening inclusion under this protocol.

* Diagnosed with a genetic immune defect
* Willing to allow genetic testing

  * 7 years old

Subjects with Severe Periodontitis of Suspected Genetic Etiology:

* History of severe periodontitis prior to age \<30
* Willing to allow genetic testing

  -\>=7 years old
* In good general health

Family members of Subjects with Severe Periodontitis of Suspected Genetic Etiology:

-Willing to allow genetic testing

-\>=7 years old

Healthy Volunteer Subjects (with/without periodontitis):

* In good general health

  -\>=18 years old
* Willing to allow genetic testing
* Have a minimum of 20 natural teeth

Inclusion Criteria for Natural History phase, all subjects:

* Diagnosis of genetic immune defect
* Presence of oral manifestation (primarily periodontitis)

Criteria for standard of care treatment:

* Active untreated disease (visible signs of tissue inflammation including erythema/edema, generalized bleeding upon probing)
* Periodontal disease defined as 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 (\>=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 Standard of Care Treatment at NIH:

* 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 advanced prosthetic needs (including implants and restorations)