OncoQuick significantly reduced the co-enriched number of MNCs, with a high tumor cell recovery rate. Processing blood from tumor patients with OncoQuick increased the chance of detecting circulating tumor cells.

Human lymphocyte antigen (HLA) associations are recognized for many autoimmune diseases, but the mechanisms are not clear. Goodpasture's disease provides a unique opportunity to investigate possible mechanisms because strong HLA associations are known, the autoantigen is well defined, and major antigen-derived peptides presented bound to HLA molecules have been identified. Therefore, it may be possible to directly analyze interactions between the antigen and HLA molecules associated with the disease, and to examine influences on antigen presentation to T cells. Towards this goal, we present a detailed analysis of HLA associations with the disease and examine molecular mechanisms that could account for them.

Class II molecules are believed to influence immune responses by selectively binding antigen-derived peptides for recognition by T cells. In Goodpasture's (antiglomerular basement membrane) disease, autoimmunity to the NC1 domain of the ␣3-chain of type IV collagen (␣3(IV)NC1) is strongly associated with HLA-DR15. We have examined the influence of the peptide binding preferences of DR15 molecules on the selection of ␣3(IV)NC1-derived peptides displayed bound to DR15 molecules on the surface of ␣3(IV)NC1-pulsed DR15-homozygous Epstein-Barr virus-transformed human B cells. The preferences of DR15 molecules were investigated using a panel of 24 overlapping peptides spanning the sequence of ␣3(IV)NC1. The ␣3(IV)NC1-derived peptides selected for display to T cells were determined by biochemical analysis as reported previously (Phelps, R. G., Turner, A. N., and Rees, A. J. (1996) J. Biol. Chem. 271, 18549 -18553).Three nested sets of naturally presented ␣3(IV)NC1 peptides were detectable bound to DR15 molecules. Peptides representative of each nested set bound to DR15 molecules, but almost two-thirds of the ␣3(IV)NC1 peptides studied had as good or better DR15 affinity than those identified as naturally processed. Thus ␣3(IV)NC1 presentation to T cells is determined more by "processing factors" than by the preferences of relatively indiscriminate DR15 molecules. The results have important implications for the use of class II peptide binding data to aid identification of potential T cell epitopes, especially for antigens which, like ␣3(IV)NC1, contain many sequences able to bind class II molecules. Antigen presenting cells (APC)1 potentially exert a profound influence on immune responses, including those to self antigens, because they regulate the way T cells recognize antigens. CD4 T cells recognize antigens in the form of processed peptides presented bound to MHC class II molecules on the surface of class II positive APC types (1, 2). These include cells important in the initiation of immune responses, such as dendritic cells, B cells, and macrophages, and cells important in regulating the T cell repertoire and self-tolerance, such as thymic epithelia. How APC select antigen-derived peptides for display to T cells therefore not only constrains the peptide specificity of responding T cells, but also influences the repertoire of T cells available to mount immune responses. Furthermore, the way APC present antigens may determine the immunodominant T cell response, which at least for some exogenous antigens is directed at the antigen-derived peptide displayed at the highest level (3). There is therefore great interest in understanding how APC generate antigen-derived peptides and make a selection for display to T cells, both as an approach to identifying T cell epitopes for specific immune modulation and toward understanding the basic biology of immune responses.APC, like many cell types, internalize extracellular proteins into their endosomal/lysosomal pathway where denaturing (low pH and reducing) conditions promote th...

Background: Autoimmune disorders including nephropathies have been reported more frequently in alemtuzumab-treated multiple sclerosis (MS) patients than in the general population. Objective: Describe instances of autoimmune nephropathy in alemtuzumab-treated MS patients. Methods: Cases were identified from safety monitoring within the alemtuzumab relapsing-remitting multiple sclerosis (RRMS) clinical development program (CDP) or post-marketing, or following off-label use. Results: As of 16 June 2017, 16 autoimmune nephropathies have occurred following alemtuzumab treatment for MS. The incidence of autoimmune nephropathies was 0.34% within the CDP (5/1485 patients). The five CDP cases (one of anti-glomerular basement membrane (anti-GBM) disease, two of membranous glomerulonephropathy, and two of serum anti-GBM antibody without typical anti-GBM disease) were identified early, responded to conventional therapy (where needed), and had favorable outcomes. Three of 11 cases outside the CDP occurred following off-label alemtuzumab use prior to approval for RRMS and were all anti-GBM disease. Diagnosis was delayed in one of these three cases and another did not receive appropriate treatment; all three cases resulted in end-stage renal failure. All anti-GBM disease cases with documented urinalysis demonstrated prior microscopic hematuria. Conclusion: Close monitoring of alemtuzumab-treated MS patients facilitates diagnosis and treatment early in the nephropathy course when preservation of renal function is more likely.