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Exploration of Immunity in Gaucher Disease

This study has been completed.
Information provided by (Responsible Party):
Ozlem Goker-Alpan, MD, O & O Alpan LLC Identifier:
First received: May 6, 2011
Last updated: April 3, 2017
Last verified: April 2017
Gaucher disease (GD), the inherited deficiency of the lysosomal enzyme glucocerebrosidase is characterized with accumulation of abnormal lipid in cells of the immune system, called macrophages. Lipid engorged macrophages, then become activated, and are also called "Gaucher cells". The mechanisms leading to macrophage activation is not fully known, however several findings in individuals with GD, such as non-specific inflammation,clinically resembling a rheumatic disease with an increased sedimentation rate, joint pain, and extreme fatigue, in addition poor wound healing, and a predisposition to diabetes may suggest an inappropriately functioning immune system in GD. The pathways leading to macrophage activation could be related to the accumulation of lipid metabolites or through the effects of other immune cells. In this study, immunologic profiling and functional assays will be performed in peripheral blood samples from patients with GD. The identification of the immunologic basis of GD will lead to the the development of new disease markers and different treatment options.

Gaucher Disease

Study Type: Observational
Study Design: Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Prospective Study of Macrophage Activation and Cross Talk Between Immune System Elements in Subjects With Gaucher Disease

Resource links provided by NLM:

Further study details as provided by O & O Alpan LLC:

Primary Outcome Measures:
  • Macrophages from patients with GD and primary immune hypo/dysfunction will show higher level of activation markers. [ Time Frame: 2 years ]

    The effect of macrophage activation on inflammation and immune response in subjects GD:

    As measured by 1) The secretion of proinflammatory cytokines/chemokines ( IL-1b, TNF, IL-6 and Mip1a ) 2) The ability of macrophages to shape the differentiation profile of naïve and memory T cells.

Biospecimen Retention:   Samples Without DNA

Enrollment: 33
Study Start Date: April 2011
Study Completion Date: May 2, 2016
Primary Completion Date: May 2, 2016 (Final data collection date for primary outcome measure)
Gaucher disease group
Subjects will include individuals with GD
Control group
Controls will include healthy individuals and individuals with primary immune dysfunction

Detailed Description:

Activated lipid engorged macrophages are the hallmark for Gaucher disease (GD). The evidence for this activation comes from the clinical finding of 1000-fold increase of serum chitotriosidase, a chitinase specifically secreted from activated macrophages. While these markers decrease with the initiation of therapy, they are not specific for organ involvement. The mechanisms of this macrophage activation is unclear, however, the presence of a non-specific inflammatory response (e.g. high sedimentation rate), poor wound healing and insulin resistance in Gaucher patients point to its clinical relevance. The finding of T, B and NK cell abnormalities in Gaucher patients also suggest either direct effects of GD lipid metabolites or indirect mechanisms via macrophages. Therefore, understanding the mechanisms of macrophage activation and the crosstalk with other immune cell types could provide mechanistic insights for pathogenesis of GD.

The investigators hypothesize that in GD the mechanisms leading macrophage activation could be related either directly to the accumulation of the lipid metabolites or through the effects of other cells of the immune system. To determine the pathways leading to macrophage dysregulation in GD, the investigators will evaluate the functional response of monocytes isolated from GD patients and profile of T cell and NK cell subsets in peripheral blood of these patients. The investigators will then assess whether macrophage dysfunction in GD is caused by an primary alteration immune response (NK and T cells response) or secondary due to the direct effects of substrate accumulation performing immunological profiling of GD patient blood samples, and through functional assays. Identification of the immunological basis of GD pathogenesis could lead to the development of both biomarkers and novel approaches for therapeutic interventions to alleviate disease symptoms. In addition, our studies will reveal novel effects of the accumulation of the lipid substrate in GD in modulating macrophage and lymphocyte subsets.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Study population will include individuals with Gaucher disease, healthy controls and individuals with primary immune dysfunction

Inclusion Criteria:

  • History of Gaucher disease
  • Nonspecific inflammatory response evidenced by an increased ESR or positive CRP
  • Positive markers for autoimmune disorders such as ANA, RF
  • Chronic inflammatory disorders such as inflammatory bowel disease
  • Otherwise would qualify for an immunological work-up such as opportunistic or unusual infections such as atypical mycobacterial infections, unexplained lymphadenopathy.

Exclusion Criteria:

  • Severe cognitive deficits impairing decision making
  • Pregnant or nursing, as these conditions may alter immunologic profile
  • History of Hepatitis B, C or HIV infections
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01358188

United States, Virginia
Lysosomal Diseases Research and Treatment Center, CFCT
Fairfax, Virginia, United States, 22030
Sponsors and Collaborators
O & O Alpan LLC
Principal Investigator: Ozlem Goker-Alpan, M.D. Center for Clinical Trials, O&O Alpan
  More Information

Additional Information:
Responsible Party: Ozlem Goker-Alpan, MD, Chief Medical Officer, O & O Alpan LLC Identifier: NCT01358188     History of Changes
Other Study ID Numbers: 10-CFCT-01
Study First Received: May 6, 2011
Last Updated: April 3, 2017

Keywords provided by O & O Alpan LLC:
Gaucher disease
macrophage activation

Additional relevant MeSH terms:
Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders processed this record on April 28, 2017