Beating the dead horse abit more

B

This week we asked “LOOKING FOR AUTOIMMUNITY, IS IT FLOGGING A DEAD HORSE?”

No sooner has our trusty Nag given its last breathe, it gets another whipping. Same story. The antibody occurs in a few people and they are against an internal proteins within a cell, suggesting an effect rather than a cause. Do I think these things cause problems? Absolutelty I do

BACKGROUND: Nuclear antigen released from central nervous system (CNS) cells undergoing destruction may induce production of antinuclear antibodies (ANA). We characterized the CNS-specific production of ANA in multiple sclerosis (MS).

METHODS: We assessed CNS-ANA binding to mouse cerebellar cell nuclei by immunofluorescence assay (IFA) with sera from 104 MS patients (91 relapsing-remitting; 13 secondary progressive), 30 patients with neuromyelitis optica spectrum disorders (NMOSD), and 30 healthy controls (HCs). Conventional ANA (cANA) was detected by IFA using human epithelial type-2 cells. CNS-ANA-positive cANA-negative patients were termed CNS-specific ANA-positive. Western blotting (WB) was performed using mouse cerebellar nuclear fractions.

RESULTS:CNS-specific ANA were more frequent in MS than in NMOSD patients or HCs (13.5% vs 0% for both comparisons, both p < .05) and were associated with HLA-DRB1*15:01 (p = .0174). WB revealed a common 55 kDa band in seven MS patients. Compared with CNS-specific ANA-negative MS patients, those with 55 kDa band-immunoreactive CNS-specific ANA showed a higher frequency of secondary progressive MS (42.9% vs 10.0%, p = .0387) and greater Expanded Disability Status Scale scores (4.50 ± 2.02 vs 2.92 ± 2.27, p = .0506).

CONCLUSIONS: The CNS-specific ANA was more frequently detected in MS patients than NMOSD patients or HCs. 55 kDa band-reactive CNS-specific ANA may reflect clinical disease progression in MS.

Whilst we are on this one, let’s look at another target and this myelin oligodendrocyte glycoprotein (MOG), we were the first group to show that it could induce a T cell response and could induce EAE, but MOG-specific antibodies could also cause demyelination if they could get into the CNS, because MOG is expressed on the surface of myelin. Then came MOG-induced EAE in C57BL/6 ( C57 black 6) mice and now the mouse EAEers think this is the target in MS. We know there is a MOG-specific variant or neuromyelitis optica, but the mousers ignore this and persists with the idea that MOG is the target and making therapies to target MOG specific antibody responses. So how common are anti-MOG antibodies in MS. According to this study, not very common. So best look elsewhere for a target.

Frequency of myelin oligodendrocyte glycoprotein antibody in multiple sclerosis: A multicenter cross-sectional study.Cobo-Calvo Á, d’Indy H, Ruiz A, Collongues N, Kremer L, Durand-Dubief F, Rollot F, Casey R, Vukusic S, De Seze J, Marignier R. Neurol Neuroimmunol Neuroinflamm. 2019 Dec 13;7(2). pii: e649. doi: 10.1212/NXI.0000000000000649. 

OBJECTIVE: To address the frequency of myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) in an unselected large cohort of adults with MS.

METHODS: This is a cross-sectional study in 2 MS expert centres (Lyon and Strasbourg University Hospitals, France) between December 1, 2017, and June 31, 2018. Patients aged ≥18 years with a definite diagnosis of MS according to 2010 McDonald criteria were tested for MOG-Ab by using a cell-based assay (CBA) in Lyon and subsequently included. Positive samples were tested by investigators blinded to the first result with a second assay in a different laboratory (Barcelona, Spain) by using the same plasmid and secondary Ab.

RESULTS: Serum samples from 685 consecutive patients with MS were analyzed for MOG-Ab. Median disease duration at sampling was 11.5 (interquartile range, 5.8-17.7) years, and 72% were women. Two (0.3%) patients resulted to be MOG-Ab-positive. The 2 patients were women aged 42 and 38 at disease onset and were diagnosed with secondary and primary progressive forms of MS, respectively. This positive result was confirmed by the CBA in Barcelona.

CONCLUSION: Our findings indicate that MOG-Ab are exceptional in MS phenotype, suggesting that the MOG-Ab testing should not be performed in typical MS presentation.

However this year we have had this

Myelin oligodendrocyte glycoprotein revisited-sensitive detection of MOG-specific T-cells in multiple sclerosis. Bronge M, Ruhrmann S, Carvalho-Queiroz C, Nilsson OB, Kaiser A, Holmgren E, Macrini C, Winklmeier S, Meinl E, Brundin L, Khademi M, Olsson T, Gafvelin G, Grönlund H. J Autoimmun. 2019 Aug;102:38-49.

Autoreactive CD4+ T-cells are believed to be a main driver of multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG) is considered an autoantigen, yet doubted in recent years. The reason is in part due to low frequency and titres of MOG autoantibodies. We demonstrate that MOG-specific T-cells are present in approximately half of persons with MS .

Only half..not enough to be a sole cause there’s something else

About the author

MouseDoctor

2 comments

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives