Circulating IgG4/IgG ASC percentages of greater than five percent are a more sensitive and reliable marker for disease activity in patients with IgG4-RD, researchers report.
Writing in a presentation given at the 2016 American College of Rheumatology annual meeting, researchers from Emory University School of Medicine reported that this measure may be a more dependable measure for both diagnosis and disease activity monitoring as opposed to elevated serum IgG4 concentrations — which are currently considered the best marker of disease activity. The results are preliminary.
Several autoimmune diseases may be considered immunoglobulin G4 related and are characterized by fibro-inflammatory involvement of multiple organs. Because masses can crop up in several organs, these diseases may mimic cancer, infections or other inflammatory immune related diseases. Currently the standard diagnostic test is an elevated serum immunoglobulin G4 concentration. The authors suggest that the immunoglobulin G4 serum marker is not reliable in that it misses the diagnosis in a large number of patients. They further hypothesize that directly measuring immunoglobulin G4 antibody secreting cells (ASCs) may be a more reliable maker for diagnosis of immunoglobulin G4 related diseases.
Study subjects included 30 patients with immunoglobulin G4 related diseases who manifested a range of disease activity, 4 patients with non-immunoglobulin G4 related diseases that had similar presentations, and 7 control subjects without disease. Serum levels of immunoglobulin G4 were measured utilizing nephelometry assays and immunoglobulin G4 antibody secreting cells were quantified with enzyme-linked immunospot assays. The authors used the immunoglobulin G4 responder index (RI) to classify 24 of the subjects as having active disease.
Analysis revealed elevated serum levels of immunoglobulin G4 in 10 of the immunoglobulin G4 related disease patients or 33% while immunoglobulin G4/immunoglobulin enzyme-linked immunospot assays >5% were found in 23 subjects or 76%. Every one of the immunoglobulin G4 related disease patients with elevated serum levels also fell in the >5% immunospot category.
The most pertinent finding was that 11 out of 13 subjects with normal serum immunoglobulin G4 levels but high numbers on the immunospot assay had active immunoglobulin g4 related disease with immunoglobulin G4 responder indices >3. Further confirming the authors hypothesis, of the patients with active disease and normal serum immunoglobulin G4 levels, 76% also had immunoglobulin G4/immunoglobulin G antibody secreting cell fractions greater than 5% in contrast to only 5 out of 21 active disease patients having elevated serum immunoglobulin G4 levels (23% r=0.23 and p=0.18). The fact that one control patient had elevated serum immunoglobulin G4 levels but a normal immunospot assay further supports the authors’ claim that the immunoglobulin G4 antibody secreting cell immunospot assay (ELISpot) improves reliability and specificity over serum immunoglobulin G4 levels for diagnosis and monitoring of disease activity in patients with immunoglobulin G4 related disease.
- Currently measuring serum levels of immunoglobulin G4 is the established method for diagnosis and monitoring of disease activity in immunoglobulin G4 related disease (IgG4-RD).
- Serum immunoglobulin G4 monitoring fails to identify many patients with immunoglobulin G4 related disease.
- Enzyme-linked immunospot assays quantifying immunoglobulin G4 antibody secreting cells were more sensitive (76%) than elevated serum immunoglobulin levels (23%) at detecting patients with active immunoglobulin G4 related disease.
- Circulating immunoglobulin G4/immunoglobulin G antibody secreting cell percentages >5% represents a more sensitive and reliable biomarker for diagnosing and monitoring disease activity in patients with immunoglobulin G4 related disease.
"Circulating IgG4 Antibody Secreting Cells Are Better Biomarker of Disease Activity Compared to Serum IgG4 Levels in Patients with IgG4-Related Disease," Arezou Khosroshahi. Nov. 13, 2016. 2016 American College of Rheumatology annual meeting. Abstract 939.