IgG4-related disease (IgG4-RD) is a recently described systemic fibro-inflammatory condition that is gaining increasing attention in the medical community due to the multidisciplinary approach required to manage a broad spectrum of clinical manifestations associated with this disease. In this disease, extracellular matrix (ECM) deposition by activated fibroblasts leads to the development of characteristic mass-forming fibrotic lesions which are ultimately responsible for the clinical manifestations observed in patients with IgG4-RD. Further interest in this novel disease entity also derives from the “reversible” nature of the characteristic tissue fibrosis, whereby, in contrast to other fibrotic disorders, ECM deposition is halted and reverted by glucocorticoid therapy.

Although some progress has been made in understanding the pathophysiology of IgG4-RD, major gaps in our knowledge remain to be filled, in particular with regard to (i) the dynamics of tissue fibrosis in the different affected organs; (ii) the mechanisms responsible for the characteristic IgG4 class-switch; and (iii) the potential underlying antigen-driven immune response(s). As a result, reliable biomarkers of diagnostic and predictive value, as well as targeted therapeutic strategies are currently lacking.

This Research Topic on IgG4-RD aims to gather a series of up-to-date manuscripts addressing the following major areas of uncertainty: (i) Pathophysiology of IgG4-RD; (ii) Biomarkers of IgG4-RD and (iii) Novel therapeutic approaches to IgG4-RD. We welcome the submission of Original Research, Review, Mini-Review, Case Reports and Clinical Trial articles that discuss the following topics:

1. Pathophysiology of IgG4-RD
(i) Interplay between the innate and adaptive immune-system and stromal cells leading to tissue fibrosis in IgG4-RD.
(ii) Autoantigens and their potential role in IgG4-RD pathobiology.
(iii) Innate immunity in the pathogenesis of IgG4-RD.
(iv) CD8 T-cells, CD4 T-helper cells, and CD4 T-follicular helper cells in the pathogenesis of IgG4-RD.
(v) B-cell compartment abnormalities in the pathogenesis of IgG4-RD.
(vi) Genetics of IgG4-RD.
(vii) Animal models for studying IgG4-RD pathogenesis.

2. Biomarkers of IgG4-RD
(i) Diagnostic biomarkers of IgG4-RD and/or of its different organ manifestations.
(ii) Predictive biomarkers for IgG4-RD response to glucocorticoids and/or other immunosuppressive therapies.
(iii) Predictive biomarkers for IgG4-RD relapse.

3. Novel therapeutic approaches to IgG4-RD treatment
(i) Animal models for exploring novel therapeutic strategies for IgG4-RD.
(ii) Clinical trials with treatments including or alternative to glucocorticoids.

Given the broad spectrum of organs involved by IgG4-RD, we encourage experts from different specialties to share their original studies and perspectives.

Keywords: IgG4 related disease, IgG4, Fibrosis, Fibrotic Inflammation

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.