Dataset Information

Humoral signatures of MOG-antibody-associated disease track with age and disease activity.

ABSTRACT: Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is an inflammatory demyelinating disease of the CNS. Although MOG is encephalitogenic in different mammalian species, the mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood. Here, we use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral immune responses in 123 patients with MOGAD. We show that age is a major determinant for MOG-antibody-related immune signatures. Unsupervised clustering additionally identifies two dominant immunological endophenotypes of MOGAD. The pro-inflammatory endophenotype characterized by increased binding affinities for activating Fcγ receptors (FcγRs), capacity to activate innate immune cells, and decreased frequencies of galactosylated and sialylated immunoglobulin G (IgG) glycovariants is associated with clinically active disease. Our data support the concept that FcγR-mediated effector functions control the pathogenicity of MOG-specific IgG and suggest that FcγR-targeting therapies should be explored for their therapeutic potential in MOGAD.

SUBMITTER: Spatola M

PROVIDER: S-EPMC9975090 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Humoral signatures of MOG-antibody-associated disease track with age and disease activity.

Spatola Marianna M Chuquisana Omar O Jung Wonyeong W Lopez Joseph A JA Wendel Eva-Maria EM Ramanathan Sudarshini S Keller Christian W CW Hahn Tim T Meinl Edgar E Reindl Markus M Dale Russell C RC Wiendl Heinz H Lauffenburger Douglas A DA Rostásy Kevin K Brilot Fabienne F Alter Galit G Lünemann Jan D JD

Cell reports. Medicine 20230119 2

Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is an inflammatory demyelinating disease of the CNS. Although MOG is encephalitogenic in different mammalian species, the mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood. Here, we use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral immune responses in 123 patients with MOGAD. We show that age is ...[more]

PMID: 36669487

Similar Datasets

Project description:IntroductionThe association of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD) and tumors has seldom been reported. We aim to investigate the occurrence of tumors in a cohort of patients with MOGAD and to describe their clinical features, in addition to previously reported cases.MethodsWe retrospectively identified patients with MOGAD (i.e., compatible clinical phenotype and positive MOG antibodies analysed with a live cell-based assay) from 1/1/2015 to 1/1/2023 who had a neoplasm diagnosed within 2 years from MOGAD onset. Furthermore, we performed systematic review of literature to identify previously reported cases. Clinical, paraclinical and oncological findings were collected and reported as median (range) or number (percentage).ResultsTwo of 150 MOGAD patients (1%) had a concomitant neoplasm in our cohort. Fifteen additional cases were retrieved from literature. Median age was 39 (16-73) years-old, 12 patients were female. ADEM (n = 4;23.5%), encephalomyelitis (n = 3;17.6%), and monolateral optic neuritis (n = 2;11.8%) were the most frequent phenotypes. Median number of treatments was 1 (range 1-4), improvement was reported in 14/17 cases (82.4%). Oncological accompaniments were teratoma (n = 4), CNS (n = 3), melanoma (n = 2), lung (n = 2), hematological (n = 2), ovary (n = 1), breast (n = 1), gastrointestinal (n = 1), and thymic (n = 1) neoplasms. Median time from tumor diagnosis to MOGAD onset was 0 (range - 60 to 20) months. MOG expression in neoplastic tissue was reported in 2/4 patients. Median PNS-CARE score was 3 (range 0-7): 11 patients were classified as "non-PNS," 5 as "possible PNS," and 1 as "probable PNS."DiscussionOur study confirms that MOG is a low-risk antibody for paraneoplastic neurological syndromes and that the clinical presentation and oncological accompaniments are extremely variable. Most of these patients were classified as non-PNS, whereas only a minority was diagnosed with possible/probable PNS, frequently in association with ovarian teratoma. These findings support the notion that MOGAD is not a paraneoplastic disease.

Project description:BackgroundMyelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS.MethodsThis is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (QAlb), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z).ResultsMOGAD patients with myelitis were more likely to have a pleocytosis, a QAlb elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, QAlb>10×10-3, as well as higher mean QAlb values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were QAlb>10×10-3 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00).ConclusionBasic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but QAlb>10×10-3 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria.

Dataset Information

Humoral signatures of MOG-antibody-associated disease track with age and disease activity.

Publications

Humoral signatures of MOG-antibody-associated disease track with age and disease activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets