Zeitschrift für Rheumatologie

, Volume 75, Issue 7, pp 681–686 | Cite as

Treatment of IgG4-related disease

Current and future approaches
  • C. A. Perugino
  • J. H. Stone


IgG4-related disease (IgG4-RD) is capable of causing great morbidity and even mortality if the condition remains undiagnosed or poorly treated, yet is typically a treatment-responsive disorder. Glucocorticoids have not been studied rigorously and practices with regard to dosing and duration of treatment remain largely empiric. In addition, IgG4-RD patients are often particularly susceptible to and intolerant of the deleterious effects of glucocorticoid therapy. B cell depletion with anti-CD20 monoclonal antibodies appears to be a rapid, effective means of obtaining disease control and limiting patients’ glucocorticoid exposure, but this option is frequently not available. Other therapies targeting the B cell lineage may also be efficacious, and one is under study. The means by which depletion or inhibition of B cells and their progeny ameliorate IgG4-RD is coming into focus now through careful mechanistic studies of samples from treated patients. The mechanistic understanding of IgG4-RD will bring an array of specific targets for therapeutic intervention. Plasmablast-directed therapy with a CD19 monoclonal antibody is currently in clinical trials. CD4 + cytotoxic T lymphocytes and fibrosis, both observed nearly universally in the tissue of IgG4-RD patients, present two unexploited vulnerabilities in controlling and even reversing the effects of the disease. Further development of such therapies is a major goal of the next few years.


B-cells Antirheumatic agents Glucocorticoids Adverse effects Monoclonal antibodies 

Behandlung IgG4-bedingter Erkrankungen

Aktuelle und zukünftige Vorgehensweisen


Eine IgG4-bedingte Erkrankung (IgG4-RD) kann eine hohe Morbidität und sogar Mortalität zur Folge haben, wenn sie nicht diagnostiziert oder falsch behandelt wird. In der Regel handelt es sich jedoch um eine Störung, die auf eine Therapie anspricht. Glukokortikoide wurden noch nicht eingehend untersucht, und Vorgehensweisen bezüglich Dosierung und Behandlungsdauer bleiben weitgehend empirisch. Zudem sind IgG4-RD-Patienten häufig besonders anfällig für die schädlichen Auswirkungen der Glukokortikoidtherapie und tolerieren diese nicht. Die B‑Zellen-Depletion mit monoklonalen Anti-CD20-Antikörpern scheint eine schnelle, effektive Maßnahme zu sein, um die Krankheit zu kontrollieren und die Exposition der Patienten gegenüber Glukokortikoiden zu begrenzen, aber diese Behandlungsmöglichkeit ist meist nicht verfügbar. Andere Therapien, welche auf die B‑Zell-Linien zielen, könnten ebenfalls wirksam sein; eine davon wird derzeit untersucht. Die Maßnahmen, durch welche die Depletion oder Inhibition von B‑Zellen und ihrer Abkömmlinge eine IgG4-RD verbessert, rückt nun durch genaue machanistische Studien von Proben behandelter Patienten in den Fokus. Das mechanistische Verständnis von IgG4-RD wird eine Vielzahl an spezifischen Zielen für therapeutische Interventionen bringen. Die Plasmablasten-gesteuerte Therapie mit einem monoklonalen CD19-Antikörper wird derzeit in klinischen Studien untersucht. Cd4 + zytotoxische T‑Zellen und Fibrose, die im Gewebe von nahezu allen IgG4-Patienten gefunden wurden, stellen bei der Kontrolle und sogar bei der Reversibilität der Auswirkungen dieser Erkrankung zwei nichtuntersuchte Schwachstellen dar. Die Weiterentwicklung solcher Therapien ist ein wesentliches Ziel der nächsten Jahre.


B-Zellen Antirheumatische Wirkstoffe Glukokortikoide Adverse effects Monoklonale Antikörper 


Compliance with ethical guidelines

Conflict of interest

C.A. Perugino state that there are no conflicts of interest. Dr. Stone has received research funding and performed consulting work in the area of IgG4-related disease for both Roche and Xencor.

The accompanying manuscript does not include studies on humans or animals.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Division of Rheumatology, Allergy, & ImmunologyMassachusetts General HospitalBostonUSA
  2. 2.Harvard Medical School; The Edward Fox Chair in MedicineMassachusetts General HospitalBostonUSA
  3. 3.Rheumatology Clinic/Yawkey 2Massachusetts General HospitalBostonUSA

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