Recombinant antibodies derived from laser captured single plasma cells of multiple sclerosis brain identified phage peptides which may be used as tools for characterizing intrathecal IgG response.Kennedy PGE, Graner MW, Walker D, Pointon T, Fringuello A, Yu X.J Neuroimmunol.2020 Jul 14;347:577319. doi: 10.1016/j.jneuroim.2020.577319. Online ahead of print.
Oligoclonal bands and increased IgG antibody levels can be detected in the cerebrospinal fluid in vast majority of patients with Multiple Sclerosis (MS). However, the antigenic specificity of oligoclonal IgG has yet to be determined. Using laser capture microdissection, we isolated single CD38+ plasma cells from lesion areas in two autopsy MS brains, and generated three recombinant antibodies (rAbs) from clonally expanded plasma cells. Panning phage-displayed random peptide libraries was carried out to determine peptide antigen specificities of these MS brain rAbs. We identified 25 high affinity phage peptides from which 5 peptides are unique. Database searches revealed that they shared sequence homologies with Epstein-Barr nuclear antigens 4 and 6, as well as with other viral proteins. Significantly, these peptides were recognized by intrathecal IgG and oligoclonal IgG bands in other MS patients. Our results demonstrate that functional recombinant antibodies can be generated from clonally expanded plasma cells in MS brain lesions by laser capture microdissection, and that these MS brain rAbs have the potential for determining the targets of intrathecal IgG and oligoclonal bands.
ProfG will be pleased that this study finds anti-EBV specific antibodis in the CNS.
However, I take issue that the specficity of oligoclonal bandshas yet to be determined. It has been done numerous times and nothing consistent has been found. On the whole they are not myelin reactive. Sometimes they find antibodies reactive with proteins from insidee cells.
However, these cells in this study were taken from sections. The technology is there to get the sequnces of individual B and T cell receptors from individual cells to address these questions
Makes you wonder if you have to work this hard to show any “specificity” how realistic these results are?
That’s another brick.
All studies I came across are always carried out on small numbers of cells/antibodies. Those studies look more like proofs of concept than aimed at unravelling the mystery.
I think that to really come to the specificity and to the originating antigen a massive approach should be applied and not on the target screening but on the antibody production. And pre-requisite is funding, a lot of funding 🙁
MDs what do you think about the fact that those studies seem to be aimed at peptides and not at glycopeptides or, in general, at modified peptides?
Bacteriophage
A bacteriophage (/bækˈtɪərioʊfeɪdʒ/), also known informally as a phage (/feɪdʒ/), is a virus that infects and replicates within bacteria and archaea. The term was derived from “bacteria” and the Greek φαγεῖν (phagein), meaning “to devour”. Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes (e.g. MS2) and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.
Bacteriophages are among the most common and diverse entities in the biosphere.[1] Bacteriophages are ubiquitous viruses, found wherever bacteria exist. It is estimated there are more than 1031 bacteriophages on the planet, more than every other organism on Earth, including bacteria, combined.[2] One of the densest natural sources for phages and other viruses is seawater, where up to 9×108 virions per millilitre have been found in microbial mats at the surface,[3] and up to 70% of marine bacteria may be infected by phages.[4]
Phages have been used since the late 20th century as an alternative to antibiotics in the former Soviet Union and Central Europe, as well as in France.[5][6] They are seen as a possible therapy against multi-drug-resistant strains of many bacteria (see phage therapy).[7] On the other hand, phages of Inoviridae have been shown to complicate biofilms involved in pneumonia and cystic fibrosis and to shelter the bacteria from drugs meant to eradicate disease, thus promoting persistent infec
10^31= 100000000000 0000000000 000000000 0
“However, I take issue that the specficity of oligoclonal bandshas yet to be determined. It has been done numerous times and nothing consistent has been found.”
Forget the notion, that there’s a single cause. There isn’t. If there was, it would have been found by now.
The only thing consistent in MS research over the past 50 years is the presence of (antibodies to) viruses, bacteria or fungi in blood, CNS or lesions.
MS is a multifactorial chronic infectious disease. I’m happy research is finally (really) starting to focus on viral infection.
Read MD2s paper to explain why
It’s a belter 😉