Plasmablast Detection From IgG4-Related Disease Patients

• ClinicalTrials.gov Identifier: NCT03466970
• Recruitment Status: Unknown
• First Posted: March 15, 2018
• Last Update Posted: March 16, 2018
• Sponsor: Meir Medical Center
• Information provided by (Responsible Party): yair levy, Meir Medical Center

Study Description

Brief Summary:

IgG4-related disease (IgG4-RD) is an immune-mediated, fibro-inflammatory disease that leads to tissue damage, organ dysfunction and, if untreated, to organ failure. The disease can affect almost any anatomic location, but the sites involved most commonly are the pancreas, salivary glands, orbital adnexa, lymph nodes, and retroperitoneum. IgG4-RD, typically diagnosed among individuals who are middle-aged, is characterized by a male predominance except with regard to organs of the head and neck (e.g., the salivary glands and orbits), where the gender distribution is approximately equal. The epidemiology of IgG4-RD remains poorly understood because of its recognition only recently as a multi-organ disease. However, IgG4-RD accounts for many conditions once regarded as disparate, single-organ disorders The purpose of our study is to evaluate the method of plasmablast measurement in peripheral blood of IgG4-RD patients, for diagnosis and follow-up on disease progression and response to treatment. This document will outline the collection, processing and testing procedures for measuring plasmablasts from IgG4-RD patients

Condition or disease
IgG4-related Disease

Detailed Description:

IgG4-related disease (IgG4-RD) is an immune-mediated, fibro-inflammatory disease that leads to tissue damage, organ dysfunction and, if untreated, to organ failure. The disease can affect almost any anatomic location, but the sites involved most commonly are the pancreas, salivary glands, orbital adnexa, lymph nodes, and retroperitoneum. IgG4-RD, typically diagnosed among individuals who are middle-aged, is characterized by a male predominance except with regard to organs of the head and neck (e.g., the salivary glands and orbits), where the gender distribution is approximately equal. The epidemiology of IgG4-RD remains poorly understood because of its recognition only recently as a multi-organ disease. However, IgG4-RD accounts for many conditions once regarded as disparate, single-organ disorders.

The current gold standard for the diagnosis of IgG4-RD is the identification of characteristic histology and immunohistochemistry features through biopsy. These pathology features are consistent across the full range of organs affected by IgG4-RD. However, histopathologic variation can occur according to the stage of the lesion; that is, longstanding disease may be predominately fibrotic and a cellular. Confirming the diagnosis of IgG4-RD in such cases can be difficult. Moreover, IgG4-RD organ pathology and IgG4-RD mimickers, such as granulomatosis with polyangiitis (formerly Wegener's), sarcoidosis, histiocytosis, and malignancies (e.g., lymphoma and adenocarcinoma of the pancreas), may share similar features including an IgG4-positive plasma cell infiltrate. Reliance upon serum IgG4 concentrations to diagnose IgG4-RD is similarly problematic because both the specificity and positive predictive value of serum IgG4 concentrations are poor.

Plasmablasts, derived from the B-cell lineage and characterized as CD19lowCD20-CD38+CD27+, comprise a stage intermediate between activated B-cells and plasma cells. Plasmablasts are generally rare in the peripheral blood of healthy individuals, but expansions are observed briefly during responses to infection or vaccination. In contrast, in the setting of autoimmunity and persistent self-antigen(s), plasmablasts can circulate for prolonged periods.

Circulating plasmablasts have been described previously in inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, and multiple myeloma. Recently, several studies identified plasmablsts in IgG4-RD both as a diagnostic tool and as an indicator of response to treatment

2. Aim

The purpose of our study is to evaluate the method of plasmablast measurement in peripheral blood of IgG4-RD patients, for diagnosis and follow-up on disease progression and response to treatment. This document will outline the collection, processing and testing procedures for measuring plasmablasts from IgG4-RD patients.

3. Plasmablast source

Plasmablasts will be isolated from peripheral blood derived from patients and normal donors who consent to participate in the study. Blood samples will be drawn by a physician or accredited nurse, transferred to the research lab in order to separate PMBCs, which will be stained for CD19lowCD20-CD38+CD27+ markers and measured by flow cytometry (FACS) located at the hematology lab

Study Design

• Study Type: Observational
• Estimated Enrollment: 40 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Plasmablast Detection From IgG4-Related Disease Patients
• Estimated Study Start Date: April 1, 2018
• Estimated Primary Completion Date: March 1, 2019
• Estimated Study Completion Date: April 1, 2019

Groups and Cohorts

Group/Cohort
IgG4 patient; 20 samples of IgG4 patients
healthy donors; 20 healthy donors

Outcome Measures

Primary Outcome Measures :

1. plasmablast measurement in peripheral blood of IgG4-RD patients [ Time Frame: 1 year ]
   Plasmablasts will be isolated from peripheral blood derived from patients and normal donors who consent to participate in the study. Blood samples will be drawn by a physician or accredited nurse, transferred to the research lab in order to separate PMBCs, which will be stained for CD19lowCD20-CD38+CD27+ markers and measured by flow cytometry (FACS) located at the hematology lab.

Biospecimen Retention:   Samples Without DNA

20 samples of IgG4 patients and 20 healthy donors

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

There will be 2 groups in the study. One group of 20 IgG4 patients and the other group is 20 healthy donors.

Criteria

Inclusion Criteria:

1. Patients that obtaining their written consent.
2. Patients above the age of 18 and referred to the Rheumatology clinic or Internal Medicine E Department at the Meir Medical Center for investigation or treatment of IgG4-RD will be candidates to participate in the study.
3. Patients at their primary diagnosis or follow up will be eligible for this study.

Exclusion Criteria:

1. Patient that not diagnosed before with IgG4.
2. patients that does not referred to the Rheumatology clinic or Internal Medicine E Department at the Meir Medical Center.

Contacts and Locations

Contacts

Contact: yael Eizikovits, Mrs; 972-09-7471936; yael.eizikovits@clalit.org.il

Locations

Israel

Yael Eizikovits

Kfar Saba, Israel, 44281

Meir health center

Kfar-saba, Israel

Sponsors and Collaborators

Meir Medical Center

Investigators

• Principal Investigator: Yair Levy, prof; head of internal medicin E

More Information

• Responsible Party: yair levy, head of internal medicin E, Meir Medical Center
• ClinicalTrials.gov Identifier: NCT03466970
• Other Study ID Numbers: 0217-17
• First Posted: March 15, 2018
• Last Update Posted: March 16, 2018
• Last Verified: March 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Immunoglobulin G4-Related Disease; Autoimmune Diseases; Immune System Diseases