Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations

Published on Jan 1, 2015in Annals of the Rheumatic Diseases16.102
· DOI :10.1136/ANNRHEUMDIS-2014-205233
Zachary S. Wallace25
Estimated H-index: 25
(Harvard University),
Hamid Mattoo21
Estimated H-index: 21
(Harvard University)
+ 7 AuthorsJohn H. Stone76
Estimated H-index: 76
(Harvard University)
Objectives We examined the utility of circulating total and IgG4+ plasmablasts as biomarkers of diagnosis and disease activity in IgG4-related disease (IgG4-RD). Materials methods We evaluated patients with active, untreated, biopsy-proven IgG4-RD affecting various organs. Flow cytometry was used to measure total plasmablast and IgG4+ plasmablast counts by gating peripheral blood for CD19lowCD38+CD20−CD27+ cells and CD19lowCD38+CD20−CD27+IgG4+ cells. Serum IgG4 concentrations were measured by nephelometry. We compared 37 IgG4-RD patients to 35 controls, including healthy individuals (n=14) and patients with other inflammatory diseases before treatment (n=21). Results The IgG4-RD patients’ mean age was 59, and 68% were male. Fourteen patients (38%) had three or more organs involved. The IgG4-RD patients had substantially elevated total plasmablast counts (median 4698/mL, range 610–79524/mL) compared to both untreated disease controls (median 592/mL, range 19–4294/mL; p  Conclusions Circulating plasmablasts are elevated in active IgG4-RD, even in patients with normal serum IgG4 concentrations. Plasmablast counts are a potentially useful biomarker for diagnosis, assessing response to treatment, and determining the appropriate time for re-treatment.
📖 Papers frequently viewed together
265 Citations
2,772 Citations
447 Citations
#1Arezou Khosroshahi (Emory University)H-Index: 30
#2Lynn A. Cheryk (Mayo Clinic)H-Index: 4
Last. John H. Stone (Harvard University)H-Index: 76
view all 6 authors...
Objective To determine the frequency of the prozone effect in patients with IgG4-related disease (IgG4-RD). Methods After identifying the prozone effect in an index patient with IgG4-RD, we examined additional samples to determine the frequency of this phenomenon. Thirty-eight serum samples obtained from patients with IgG4-RD whose results had been reported previously were retested. The serum IgG4 concentrations determined by this repeat analysis were compared with the originally reported values...
81 CitationsSource
#1Phil A. Hart (Mayo Clinic)H-Index: 25
#2Mark Topazian (Mayo Clinic)H-Index: 53
Last. Suresh T. Chari (Mayo Clinic)H-Index: 83
view all 14 authors...
Background There is a paucity of data on long-term management of type 1 autoimmune pancreatitis (AIP), a relapsing steroid-responsive disorder. Objective We describe our experience with treatment of relapses and maintenance of remission using steroid-sparing immunomodulators (IMs) and induction of remission using rituximab (RTX). Methods We obtained details of disease relapse and treatment in 116 type 1 AIP patients from clinic visits, medical records and telephone interviews. We compared relaps...
235 CitationsSource
#1Priscilla F Kerkman (LEI: Leiden University)H-Index: 6
#2Yoann Rombouts (LEI: Leiden University)H-Index: 24
Last. Hans Scherer (LEI: Leiden University)H-Index: 34
view all 7 authors...
Objective To study the characteristics and phenotype of anticitrullinated protein antibody (ACPA)-specific B cells in peripheral blood of patients with rheumatoid arthritis (RA). Methods Peripheral blood B cells from ACPA-positive patients with RA were cultured with or without stimulating factors. Following culture, supernatants were assessed for the presence of ACPA-IgG and non-specific total IgG by ELISA. Results Following stimulation, ACPA were detectable in up to 100% of culture wells. Of in...
45 CitationsSource
#1Isabel Brenner (University of Würzburg)H-Index: 1
#2Sabine Roth (University of Würzburg)H-Index: 14
Last. Eva Geissinger (University of Würzburg)H-Index: 23
view all 6 authors...
Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression
55 CitationsSource
#2Marieke E. Doorenspleet (UvA: University of Amsterdam)H-Index: 15
Last. Ulrich BeuersH-Index: 66
view all 9 authors...
Immunoglobulin G4 (IgG4)-associated cholangitis (IAC) is a manifestation of the recently discovered idiopathic IgG4-related disease. The majority of patients have elevated serum IgG4 levels and/or IgG4-positive B-cell and plasma cell infiltrates in the affected tissue. We hypothesized that clonally expanded, class-switched IgG4-positive B cells and plasma cells could be causal to these poorly understood phenomena. In a prospective cohort of six consecutive IAC patients, six healthy controls, and...
97 CitationsSource
#1Yui Shimizu (Sapporo Medical University)H-Index: 10
#2Motohisa Yamamoto (Sapporo Medical University)H-Index: 35
Last. Yasuhisa Shinomura (Sapporo Medical University)H-Index: 66
view all 20 authors...
Objective. Despite ongoing research, the clinical and histopathological natural history of immunoglobulin (Ig) G4-related disease (IgG4-RD) remains unclear and the optimal time to initiate treatment is unknown. A focus on clinical symptoms rather than image finding is recommended for therapeutic initiation in autoimmune pancreatitis, but evidence for this approach is lacking. We aimed to retrospectively analyse disease duration, efficacy of treatment with glucocorticoids and results of histopath...
76 CitationsSource
The hallmarks of IgG4-related disease (IgG4-RD) are lymphoplasmacytic tissue infiltration with a predominance of IgG4-positive plasma cells, accompanied by fibrosis, obliterative phlebitis, dacryoadenitis, and elevated levels of IgG4. In a recent issue of Arthritis Research & Therapy, Tsuboi and colleagues demonstrated that regulatory T (Treg) cell-and T helper 2 (Th2) cell-derived cytokines contribute to the pathogenesis of Mikulicz's disease, an activation pathway that appears to be common for...
8 CitationsSource
#1John H. Stone (Harvard University)H-Index: 76
#2John K.C. ChanH-Index: 45
Last. Yoh ZenH-Index: 69
view all 6 authors...
IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by an elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4-RD encompasses a wide variety of diseases, formerly diagnosed as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), hypophysitis, Riedel thyroiditis, tubulointerstitial nephritis, prostatitis, retroperitoneal fibrosis, inflammatory aortic aneurysm and inflammatory pseudotumor. However, like a crow f...
365 CitationsSource
#1Shigeru Iwata (University of Occupational and Environmental Health Japan)H-Index: 22
#2Kazuyoshi Saito (University of Occupational and Environmental Health Japan)H-Index: 42
Last. Yoshiya Tanaka (University of Occupational and Environmental Health Japan)H-Index: 70
view all 4 authors...
Immunoglobulin G4-related disease (IgG4RD) is a novel clinical disease entity characterised by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells.1 ,2 Interleukin 4 (IL-4) and IL-10, which were detected with B cells in the salivary gland in this disease,3 direct naive B cells to switch to IgG4 production.4 B cells are therefore considered to be important for the pathogenesis of IgG4RD. However, the phenotype of B cells in patients with IgG4RD remains elusive. In this repor...
10 CitationsSource
#1Nicole J. Tarlton (SJSU: San Jose State University)H-Index: 3
#2Caroline Green (SJSU: San Jose State University)H-Index: 1
Last. Tzvia Abramson (SJSU: San Jose State University)H-Index: 5
view all 9 authors...
Background: The incidence of pediatric ulcerative colitis (UC), a chronic autoinflammatory disease of the colon, is on the rise. Although an increased infiltration of B cells from the peripheral blood into the colon occurs in UC, B-cell trafficking is understudied. We hypothesized that the frequency of circulating plasmablasts (PBs) and their trafficking receptor (TR) expression may be indicative of the location and degree of pathology in pediatric UC. Methods: We conducted multicolor flow cytom...
17 CitationsSource
Cited By278
#1Ummusen Kaya Akca (Hacettepe University)H-Index: 3
#2Erdal Atalay (Hacettepe University)H-Index: 2
Last. Yelda Bilginer (Hacettepe University)H-Index: 25
view all 10 authors...
Objective Immunoglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated, and fibroinflammatory disease that can affect almost any organ system. We aimed to present our single-center experience of pediatric patients with IgG4-RD, a rare disease in children. Methods Pediatric patients diagnosed with IgG4-RD at the Hacettepe University between June 2014 and September 2020 were evaluated retrospectively. Patients with definite, probable, or possible diagnosis of IgG4-RD were included. R...
#2A. Pérez GómezH-Index: 2
Last. M. Álvarez-Mon SotoH-Index: 3
view all 4 authors...
#1G. Saitakis (MEE: Massachusetts Eye and Ear Infirmary)
#2Bart K Chwalisz (Harvard University)H-Index: 5
Abstract Purpose of review IgG4-related disease (IgG4-RD) is emerging as a fibro-inflammatory entity affecting multiple organs, including manifold neurologic manifestations. This review discusses general characteristics of IgG4-RD neurologic disease including epidemiology, histology, clinical picture and treatment approaches. Recent findings IgG4-RD is increasingly recognized as an important underlying pathophysiology in multiple disorders of neurologic interest, including orbital inflammation, ...
#1Marco Lanzillotta (UniSR: Vita-Salute San Raffaele University)H-Index: 14
#2Andreu Fernández-Codina (UWO: University of Western Ontario)H-Index: 9
Last. Emanuel Della-Torre (UniSR: Vita-Salute San Raffaele University)H-Index: 25
view all 7 authors...
INTRODUCTION Awareness of IgG4-related disease (IgG4-RD) is increasing worldwide and specialists are now familiar with most of its clinical manifestations and mimickers. IgG4-RD promptly responds to glucocorticoids and repeated courses are typically used to induce and maintain remission because the disease relapses in most patients. If left untreated it can lead to organ dysfunction, organ failure and death. Advancement in our understanding of IgG4-RD pathogenesis is leading to the identificatio...
Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Respo...
#1Han Joo Kim (UOU: University of Ulsan)
#2Eunkyoung You (Inje University)H-Index: 1
Last. Chan-Jeoung Park (UOU: University of Ulsan)H-Index: 19
view all 4 authors...
Resumen La enfermedad relacionada con IgG4 (ER-IgG4) es una enfermedad sistemica reconocida. Se describio tras observarse que pacientes diagnosticados de pancreatitis autoinmune mostraban signos de enfermedad extrapancreatica. La clinica de estos pacientes es subaguda y se manifiesta por aparicion de lesiones seudotumorales, o tumores inflamatorios o fibrosos. En ocasiones, puede ser grave, como en el caso de pacientes con colangitis o vasculitis de gran vaso. Los criterios diagnosticos incluyen...
Resumen La enfermedad relacionada con IgG4 (ER-IgG4) es una enfermedad sistemica reconocida. Se describio tras observarse que pacientes diagnosticados de pancreatitis autoinmune mostraban signos de enfermedad extrapancreatica. La clinica de estos pacientes es subaguda y se manifiesta por aparicion de lesiones seudotumorales, o tumores inflamatorios o fibrosos. En ocasiones, puede ser grave, como en el caso de pacientes con colangitis o vasculitis de gran vaso. Los criterios diagnosticos incluyen...
#1Natalie Louise Simon (University of Bedfordshire)
#2Mostafa Negmeldin (University of Bedfordshire)
IgG4-related disease is a rheumatological disorder, affecting multiple organ systems, and displaying dense lymphoplasmacytic inflammatory infiltrate and storiform fibrosis on histology. The pulmonary manifestations of IgG4-related disease are varied. Most commonly, bronchovascular consolidation and perilymphatic parenchymal thickening occur. IgG4-related disease can present as a solitary parenchymal mass and is often mistaken for a primary pulmonary or haematological malignancy. This report pres...