Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis.

The complement pathway has potential contributions to both white (WM) and grey matter (GM) pathology in Multiple Sclerosis (MS). A quantitative assessment of complement involvement is lacking. Here we describe the use of Tissue MicroArray (TMA) methodology in conjunction with immunohistochemistry to investigate the localization of complement pathway proteins in progressive MS cortical GM and subcortical WM. Antibodies targeting complement proteins C1q, C3b, regulatory proteins C1 inhibitor (C1INH, complement receptor 1 (CR1), clusterin, factor H (FH) and the C5a anaphylatoxin receptor (C5aR) were utilised alongside standard markers of tissue pathology. All stained slides were digitised for quantitative analysis. We found that numbers of cells immunolabelled for HLA-DR, GFAP, C5aR, C1q and C3b were increased in WM lesions (WML) and GM lesions (GML) compared to normal appearing WM (NAWM) and GM (NAGM), respectively. The complement regulators C1INH, CR1, FH and clusterin were more abundant in WM lesions, while the number of C1q+ neurons were increased and the number of C1INH+, clusterin+, FH+ and CR1+ neurons decreased in GM lesions. The number of complement component positive cells (C1q, C3b) correlated with complement regulator expression in WM, but there was no statistical association between complement activation and regulator expression in the GM. We conclude that TMA methodology and quantitative analysis provides evidence of complement dysregulation in MS GML, including an association of the numerical density of C1q+ cells with tissue lesions. Our work confirms that complement activation and dysregulation occur in all cases of progressive MS and suggest that complement may provide potential biomarkers of the disease.

When Medical News Comes from Press Releases-A Case Study of Pancreatic Cancer and Processed Meat.

The media have a key role in communicating advances in medicine to the general public, yet the accuracy of medical journalism is an under-researched area. This project adapted an established monitoring instrument to analyse all identified news reports (n = 312) on a single medical research paper: a meta-analysis published in the British Journal of Cancer which showed a modest link between processed meat consumption and pancreatic cancer. Our most significant finding was that three sources (the journal press release, a story on the BBC News website and a story appearing on the 'NHS Choices' website) appeared to account for the content of over 85% of the news stories which covered the meta analysis, with many of them being verbatim or moderately edited copies and most not citing their source. The quality of these 3 primary sources varied from excellent (NHS Choices, 10 of 11 criteria addressed) to weak (journal press release, 5 of 11 criteria addressed), and this variance was reflected in the accuracy of stories derived from them. Some of the methods used in the original meta-analysis, and a proposed mechanistic explanation for the findings, were challenged in a subsequent commentary also published in the British Journal of Cancer, but this discourse was poorly reflected in the media coverage of the story.