Lots of Targets for Autoantibodies

Ayoglu B, Haggmark A, Khademi M, Olsson T, Uhlen M, Schwenk JM, Nilsson P. Autoantibody profiling in multiple sclerosis using arrays of human protein fragments. Mol Cell Proteomics. 2013 Jun 3. [Epub ahead of print]

Profiling the autoantibody repertoire with proteome-wide antigen collections is emerging as a powerful tool for the identification of biomarkers for autoimmune diseases. Here, a systematic and undirected approach was taken to screen for profiles of IgG in human plasma from 90 individuals withmultiple sclerosis (MS) related diagnoses. Reactivity pattern of 11,520 antigens (corresponding to ~38% of all human protein encoding genes) were generated on planar protein microarrays built within the Human Protein Atlas. IgG reactivity was observed towards more than 2,000 antigens, among which 64% were recognized only in single individuals. Reactivity distributions among MS subgroups were used to select 384 antigens, which were then re-evaluated on planar microarrays, corroborated with suspension bead arrays in a larger cohort (n=376), and confirmed for specificity in inhibition assays. Among the heterogeneous pattern within and across MS subtypes, differences in recognition frequencies were found for 51 antigens, which were enriched for proteins of transcriptional regulation. In conclusion, a strategy on complementary high-throughput protein array platforms facilitated the discovery and verification of disease-associated autoimmunity signatures that are proposed as additional antigens for larger scaled validation across MS biobanks.

On a day when we have one study using a few peptides to try and stop myelin autoimmunity we have another study looking at the number of potential targets as assessed by antibodies in the blood and brain fluid. They create chips that contained about 7,500 antigens about 38% of the genome. Did they find myelin basis protein and few antigens were a problem well they got 182 different targets in SPMSers, and 150-160 in RRMSers some were more common and were often targets inside a cell, which an antibody would not get to until a cell maybe destroyed….but they were not typically myelin antigens. Is this so much for the myelin autoimmunity hypothesis. Many of these will be a conseqeunce of the problem and not the cause of the problem and will be generated to help mop up the products of damaged cells. 

However, the aim to immunologically tolerise (silence immune reactive cells) just a few antigens may be too simplistic unless there is a hierachy. However, I think this is the case where you can deal with the main players and you take out the influence of the minor players.

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