Article Text

PDF
Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.
  1. Anita S Y Chan1,2,
  2. Hardeep Mudhar3,
  3. Sunny Yu Shen1,
  4. Stephanie S Lang1,
  5. Malee Fernando4,
  6. Maryam Hazly Hilmy2,
  7. Naomi Jayne Guppy5,
  8. Ian Rennie6,7,
  9. Lisa Dunkley8,
  10. Issam Al Jajeh2
  1. 1Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
  2. 2Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
  3. 3Department of Histopathology, Royal Hallamshire Hospital, National Specialist Ophthalmic Pathology Service (NSOPS), Sheffield, UK
  4. 4Department of Histopathology, Singapore General Hospital, Singapore
  5. 5Department of Advanced Diagnostics, University College London, London, UK
  6. 6Academic Unit of Ophthalmology and orthoptics, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK
  7. 7Department of Oncology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK
  8. 8Department of Rheumatology, Royal Hallamshire Hospital, Sheffield, UK
  1. Correspondence to Dr Anita S Y Chan, Level 8, Ocular Pathology Service, Singapore National Eye Centre, 11 Third Hospital Avenue, 168751 Singapore; anita.chan.s.y{at}snec.com.sg

Abstract

Aims To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders.

Methods This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016. Clinical information and histology were reviewed and cases were classified into three groups: Group 1: IgG4-RD orbital inflammation (n=43); Group 2: idiopathic OID (n=12) and Group 3: autoimmune OID (n=14). Serum IgG1, IgG2, IgG3 and IgG4 levels were collated where available and immunohistochemistry (IHC) for tissue IgG2 plasma cells was performed.

Results Dual IHC showed IgG2 plasma cells as a distinct population from IgG4 plasma cells. Significant (twofold) serum IgG2 elevation was noted among IgG4-RD (group 1), idiopathic (group 2) and autoimmune OID (group 3). Similarly, significant elevation of tissue IgG2 plasma cells was also seen among IgG4-RD (group 1), idiopathic and autoimmune OID (groups 2 and 3).

Conclusions Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the ‘IgG4-RD’ pathogenesis.

  • IgG4-related disease (IgG4-RD)
  • orbital inflammatory disorders (OID)
  • IgG4
  • IgG2

Statistics from Altmetric.com

Footnotes

  • Contributors ASYC and HM conceived the idea of the paper and are joint first authors.

    ASYC, HM, MF, SYS, IR, LD and IAJ helped collate the clinical and histological data.

    MHH and NJG performed the immunohistochemistry and technical aspects.

    SSL performed the statistical analysis.

    All authors reviewed and commented on the paper.

  • Funding This research was funded by the Singapore National Eye Centre, Health Research Endowment Fund (HREF) Grant R1210/16/2015.

  • Competing interests None declared.

  • Ethics approval Institutional Review Board from Royal Hallamshire Hospital and Singapore General Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • At a glance
    Keith Barton James Chodosh Jost B Jonas