Plasmablast Detection From IgG4-Related Disease Patients

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

Study Overview

• Status: Unknown
• Conditions: 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 Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: yael Eizikovits, Mrs; Phone Number: 972-09-7471936; Email: yael.eizikovits@clalit.org.il

Study Locations

• Israel
  • Kfar Saba, Israel, 44281
    • Yael Eizikovits
  • Kfar-saba, Israel
    • Meir health center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasmablast measurement in peripheral blood of IgG4-RD patients	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.	1 year

Collaborators and Investigators

• Sponsor: Meir Medical Center
• Investigators: Principal Investigator: Yair Levy, prof, head of internal medicin E

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2018
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): April 1, 2019

Study Registration Dates

• First Submitted: February 25, 2018
• First Submitted That Met QC Criteria: March 14, 2018
• First Posted (Actual): March 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 16, 2018
• Last Update Submitted That Met QC Criteria: March 15, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Immunoglobulin G4-Related Disease
• Other Study ID Numbers: 0217-17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No