Conjecture: Some auto-immune diseases are caused by the tissue, not a problem with the immune system

Applying highly sensitive modern immune profiling techniques to the blood or inflamed tissue of auto-immune patients with one of the common T-cell mediated diseases fails to detect large clonal expansions or other signs of a dysregulated immune system. Additionally, these new methods have shown that self-reactive Tcells are found in the periphery (and are not completely negatively selected in the thymus as previously believed). Combining these new data with well-established studies in auto-immunity leads to the conjecture that certain auto-immune diseases are likely to be caused by defects in tissue, not by dysregulation of the adaptive immune system. In particular, one hypothesis is that specific tissues up-regulate HLA class 2 genes, presenting epitopes that are bound by CD4 + helper T cells, which facilitates an immune response against the tissue specific cells. peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/032300 doi: bioRxiv preprint first posted online Nov. 20, 2015;