Eye and Immunogenetic Features of Sarcoidosis
| Status: | Completed |
|---|---|
| Conditions: | Cervical Cancer, Endocrine |
| Therapuetic Areas: | Endocrinology, Oncology |
| Healthy: | No |
| Age Range: | 6 - Any |
| Updated: | 4/21/2016 |
| Start Date: | September 2006 |
| End Date: | December 2007 |
Ocular and Immuno-Genetic Manifestations of Sarcoidosis
This study will evaluate patients with sarcoidosis to understand how the disease affects the
body. Sarcoidosis is a disease that results from inflammation of body tissues. The lungs,
lymph nodes in the chest, skin and eyes are most commonly affected. As the disease
progresses, small lumps, or granulomas, appear in the affected tissues. In most cases, the
granulomas clear up, but in cases where they do not heal and disappear, the tissues tend to
remain inflamed. Eye inflammation (uveitis) associated with sarcoidosis can cause various
eye diseases, sometimes leading to blindness. This study will examine the clinical,
immunological and genetic features of ocular sarcoidosis.
Patients 6 years of age and older with sarcoidosis may be eligible for this study.
Candidates are screened with the following procedures:
- Completion of a questionnaire with medical, social and demographic information
- Blood draw for laboratory tests
- Complete eye examination, including measurement of eye pressure and dilation of the
pupils to examine the back of the eye. Fluorescein angiography may be done. This test
involves injecting a dye into a vein in the arm. The dye travels to the blood vessels
in the eyes. A camera flashes a blue light into the eye and takes pictures of the
retina that show whether the dye has leaked from the blood vessels into the retina.
Other photographs of the eye may also be taken using a special camera.
Participants are followed in conjunction with their local eye doctor as required by the
status of their disease. Patients whose disease is stable are seen for an initial
examination and followed every 12 months for 3 years.
body. Sarcoidosis is a disease that results from inflammation of body tissues. The lungs,
lymph nodes in the chest, skin and eyes are most commonly affected. As the disease
progresses, small lumps, or granulomas, appear in the affected tissues. In most cases, the
granulomas clear up, but in cases where they do not heal and disappear, the tissues tend to
remain inflamed. Eye inflammation (uveitis) associated with sarcoidosis can cause various
eye diseases, sometimes leading to blindness. This study will examine the clinical,
immunological and genetic features of ocular sarcoidosis.
Patients 6 years of age and older with sarcoidosis may be eligible for this study.
Candidates are screened with the following procedures:
- Completion of a questionnaire with medical, social and demographic information
- Blood draw for laboratory tests
- Complete eye examination, including measurement of eye pressure and dilation of the
pupils to examine the back of the eye. Fluorescein angiography may be done. This test
involves injecting a dye into a vein in the arm. The dye travels to the blood vessels
in the eyes. A camera flashes a blue light into the eye and takes pictures of the
retina that show whether the dye has leaked from the blood vessels into the retina.
Other photographs of the eye may also be taken using a special camera.
Participants are followed in conjunction with their local eye doctor as required by the
status of their disease. Patients whose disease is stable are seen for an initial
examination and followed every 12 months for 3 years.
BACKGROUND
Sarcoidosis is a multi-systemic granulomatous disease. The lungs, thoracic lymph nodes, the
skin and the eyes are the most commonly affected organs. Most patients with sarcoidosis
present with respiratory symptoms. Sarcoid uveitis is usually suspected when ocular
inflammation is found in conjunction with suggestive serological and radiological studies.
Currently, the diagnosis of sarcoidosis requires the demonstration of non-caseating
granulomas on biopsy; but even this is not always diagnostic; more sensitive and specific
noninvasive tools are needed.
Ophthalmic involvement has been reported in as many as 40% of patients with sarcoidosis, but
most series report ophthalmic findings in approximately 25% of patients who develop chronic,
systemic sarcoidosis. Uveitis associated with sarcoidosis can be very diverse, including:
acute non-granulomatous or chronic granulomatous iridocyclitis, vitritis, retinal
vasculitis, choroiditis with choroidal granulomas and papillitis secondary to optic nerve
granulomas; and it can cause ocular morbidity due to a high incidence of glaucoma and
cataracts. Other ophthalmic findings include lacrimal gland enlargement, secondary Sjogren's
disease, scleritis, orbital gland involvement, secondary proliferative retinopathy,
subretinal neovascularization, and optic neuropathy.
To better evaluate and diagnose patients, we also need to improve our ability to predict
susceptibility and prognosis, especially among African-Americans. Current epidemiologic
studies of sarcoidosis indicate that in the United States, African Americans have about a
threefold higher age-adjusted annual incidence, 35.5/100,000, compared with Caucasians,
10.9/100,000. In addition, African Americans with chronic sarcoidosis are more likely to
develop ocular manifestations than whites. The study of ocular sarcoidosis is important
because it is a leading inflammatory cause of blindness and ocular morbidity. In large
surveys of patients with uveitis, approximately 5% of patients were found to have ocular
sarcoidosis, and approximately 10% of these patients become blind in at least one eye.
AIMS:
AIM 1: CLINICAL ANALYSIS:
Documentation of:
1. Clinical features of sarcoidosis associated uveitis
2. Chronological association of ocular disease to histopathologic diagnosis of sarcoidos
3. Family history of sarcoidosis
4. Previous therapies and response
5. Ocular status compared with systemic disease status, current and historical
Environmental exposure history
AIM 2: IMMUNOLOGICAL ANALYSIS:
One of the goals of this study is to determine the diagnostically important cytokines in
biopsy-proven ocular sarcoidosis.
The chemokine profile of the Peripheral Blood Mononuclear Cells and Broncho-Alveolar Lavage
Fluid (BALF) of pulmonary sarcoidosis patients has been reported and many cytokines have
been implicated in the pathogenesis of this disease.
1. Serum Level for
A. TNF alpha
B. MIP-1 alpha
C. IL-8
D. IL-2
E. TGF Beta
F. INF gamma
2. Immunophenotyping of whole blood cells and BALF by flow cytometry
Focus on:
A. T cell sub-typing (examples: CD4, CD8)
B. NK cell sub-typing (examples:CD56, KIR)
3. TLRs sub-typing
AIM 3: GENETIC ANALYSIS:
Serum analysis for HLA Class I and II typing
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis
and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the
National Heart Lung and Blood Institute.
FUTURE AIMS:
We aim to characterize the TLR activation profile in patients with ocular sarcoidosis, and
compare them to patients with pulmonary sarcoidosis and normal volunteers. Using this
immuno-genetic classification scheme, in conjunction with HLA typing, we hope to develop
novel diagnostic and/or prognostic criteria for sarcoidosis. In addition, the TLR activation
profile may allow risk stratification for different sarcoidosis phenotypes.
METHODS:
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis
and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the
National Heart Lung and Blood Institute. After obtaining informed consent, the patients will
be invited to participate in the study. After appropriate enrollment, they will undergo the
following
1. Completion of a questionnaire, with medical, social and demographic data
2. A complete ophthalmologic examination
3. Baseline serologic analysis
4. Baseline serum analysis for immunologic analysis
5. HLA-Typing
6. Patients who are quiescent will be seen at baseline with a second visit at 1 year
7. Patients who are active will be treated appropriately, by their referring
ophthalmologist or on a treatment protocol at the National Eye Institute
Sarcoidosis is a multi-systemic granulomatous disease. The lungs, thoracic lymph nodes, the
skin and the eyes are the most commonly affected organs. Most patients with sarcoidosis
present with respiratory symptoms. Sarcoid uveitis is usually suspected when ocular
inflammation is found in conjunction with suggestive serological and radiological studies.
Currently, the diagnosis of sarcoidosis requires the demonstration of non-caseating
granulomas on biopsy; but even this is not always diagnostic; more sensitive and specific
noninvasive tools are needed.
Ophthalmic involvement has been reported in as many as 40% of patients with sarcoidosis, but
most series report ophthalmic findings in approximately 25% of patients who develop chronic,
systemic sarcoidosis. Uveitis associated with sarcoidosis can be very diverse, including:
acute non-granulomatous or chronic granulomatous iridocyclitis, vitritis, retinal
vasculitis, choroiditis with choroidal granulomas and papillitis secondary to optic nerve
granulomas; and it can cause ocular morbidity due to a high incidence of glaucoma and
cataracts. Other ophthalmic findings include lacrimal gland enlargement, secondary Sjogren's
disease, scleritis, orbital gland involvement, secondary proliferative retinopathy,
subretinal neovascularization, and optic neuropathy.
To better evaluate and diagnose patients, we also need to improve our ability to predict
susceptibility and prognosis, especially among African-Americans. Current epidemiologic
studies of sarcoidosis indicate that in the United States, African Americans have about a
threefold higher age-adjusted annual incidence, 35.5/100,000, compared with Caucasians,
10.9/100,000. In addition, African Americans with chronic sarcoidosis are more likely to
develop ocular manifestations than whites. The study of ocular sarcoidosis is important
because it is a leading inflammatory cause of blindness and ocular morbidity. In large
surveys of patients with uveitis, approximately 5% of patients were found to have ocular
sarcoidosis, and approximately 10% of these patients become blind in at least one eye.
AIMS:
AIM 1: CLINICAL ANALYSIS:
Documentation of:
1. Clinical features of sarcoidosis associated uveitis
2. Chronological association of ocular disease to histopathologic diagnosis of sarcoidos
3. Family history of sarcoidosis
4. Previous therapies and response
5. Ocular status compared with systemic disease status, current and historical
Environmental exposure history
AIM 2: IMMUNOLOGICAL ANALYSIS:
One of the goals of this study is to determine the diagnostically important cytokines in
biopsy-proven ocular sarcoidosis.
The chemokine profile of the Peripheral Blood Mononuclear Cells and Broncho-Alveolar Lavage
Fluid (BALF) of pulmonary sarcoidosis patients has been reported and many cytokines have
been implicated in the pathogenesis of this disease.
1. Serum Level for
A. TNF alpha
B. MIP-1 alpha
C. IL-8
D. IL-2
E. TGF Beta
F. INF gamma
2. Immunophenotyping of whole blood cells and BALF by flow cytometry
Focus on:
A. T cell sub-typing (examples: CD4, CD8)
B. NK cell sub-typing (examples:CD56, KIR)
3. TLRs sub-typing
AIM 3: GENETIC ANALYSIS:
Serum analysis for HLA Class I and II typing
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis
and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the
National Heart Lung and Blood Institute.
FUTURE AIMS:
We aim to characterize the TLR activation profile in patients with ocular sarcoidosis, and
compare them to patients with pulmonary sarcoidosis and normal volunteers. Using this
immuno-genetic classification scheme, in conjunction with HLA typing, we hope to develop
novel diagnostic and/or prognostic criteria for sarcoidosis. In addition, the TLR activation
profile may allow risk stratification for different sarcoidosis phenotypes.
METHODS:
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis
and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the
National Heart Lung and Blood Institute. After obtaining informed consent, the patients will
be invited to participate in the study. After appropriate enrollment, they will undergo the
following
1. Completion of a questionnaire, with medical, social and demographic data
2. A complete ophthalmologic examination
3. Baseline serologic analysis
4. Baseline serum analysis for immunologic analysis
5. HLA-Typing
6. Patients who are quiescent will be seen at baseline with a second visit at 1 year
7. Patients who are active will be treated appropriately, by their referring
ophthalmologist or on a treatment protocol at the National Eye Institute
- INCLUSION CRITERIA:
1. Participants must be at least 6 years old
2. Participants must have biopsy-proven sarcoidosis
3. Participant must be able to consent to participating in the protocol
4. For minors, consent by an adult will be necessary
EXCLUSION CRITERIA:
We will exclude participants who are unable or unwilling to give blood at the designated
times in the protocol
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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