Refining cell-based assay to detect MOG-IgG in patients with central nervous system inflammatory diseases

Journal article

Background

Given that the spectrum of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated disease is yet to be fully defined, development of sensitive and highly specific assays to identify MOG-IgG is crucial to precisely define the clinical phenotypes, disease courses and prognosis to describe the full spectrum of MOG-IgG associated diseases. Here, we aim to validate a new in-house live cell-based assay (CBA) for screening MOG-IgG in patients with central nervous system inflammatory diseases.

Methods

We generated a full length MOG transfected HEK293 stable cell line using pIRES2-eGFP vector. Sera from 355 patients with central nervous system inflammatory diseases and 25 healthy individuals were evaluated for MOG-IgG seropositivity using in-house cell-based immunofluorescence assay (CBA-IF). The specificity of IgG ( H + L) and IgG1-Fc secondary antibodies as well as IgM binding were determined by cell-based flow cytometry (CBA-FACS). The optimal cut-offs for determining seropositivity in CBA-FACS were calculated and the concordance of CBA-IF score and CBA-FACS was studied. The results of our CBA-IF were compared with the Oxford CBA-IF.

Results

11.5% (41/355) of patients were seropositive for MOG-IgG and had clinical phenotypes that were within the known clinical spectrum of MOG-IgG associated diseases. No typical multiple sclerosis patients, aquaporin-4-IgG positive neuromyelitis optica spectrum disorder or healthy individuals were MOG-IgG seropositive. Using CBA-FACS, the anti-human IgG ( H + L) was found to be comparable to IgG1-Fc antibody. No IgM binding was observed in all the samples tested. CBA-IF score and CBA-FACS yielded high correlation. The concordance of the NCC CBA-IF with the Oxford CBA-IF was 98%.

Conclusion

We have developed MOG-IgG CBAs that have different characteristics and benefits but with high specificity and concordance. The complementary use of two methods and follow-up study with larger cohort will increase the clinical usefulness of MOG-IgG CBAs.

Authors: Kim, Y; Hyun, J-W; Woodhall, MR; Oh, Y-M; Lee, J-E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Multiple Sclerosis and Related Disorders
• Volume: 40
• Pages: 101939
• Publication date: 2020-01-09
• Acceptance date: 2020-01-07
• DOI: 10.1016/j.msard.2020.101939
• EISSN: 2211-0356
• ISSN: 2211-0348
• Language: English
• Keywords: FFR; cell-based assay; MOG-IgG; MOG-IgG associated diseases; MOG-IgG assay