Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment

• Published in: British journal of ophthalmology Vol. 101; no. 11; pp. 1576 - 1582
• Main Authors: Chan, Anita S Y, Mudhar, Hardeep, Shen, Sunny Yu, Lang, Stephanie S, Fernando, Malee, Hilmy, Maryam Hazly, Guppy, Naomi Jayne, Rennie, Ian, Dunkley, Lisa, Al Jajeh, Issam
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.11.2017
• Subjects: Adult; Aged; Aged, 80 and over; Autoimmune diseases; Autoimmune Diseases - diagnosis; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Binding sites; Biopsy; Eye diseases; Female; Follow-Up Studies; Humans; Immunoglobulin G - blood; Immunoglobulins; Immunohistochemistry; Inflammation; Lymphoma; Male; Middle Aged; Ophthalmology; Orbit - metabolism; Orbit - pathology; Orbital Pseudotumor - diagnosis; Orbital Pseudotumor - immunology; Orbital Pseudotumor - metabolism; Pathology; Plasma Cells - immunology; Plasma Cells - metabolism; Retrospective Studies; Thyroid gland; Young Adult; United Kingdom > UK; Singapore; IgG4; IgG4-related disease (IgG4-RD); IgG2; orbital inflammatory disorders (OID)
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjophthalmol-2017-310148

AimsTo 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.MethodsThis 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.ResultsDual 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).ConclusionsSignificant 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.