Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome.

Humans cannot synthesize N-glycolylneuraminic acid (Neu5Gc) but dietary Neu5Gc can be absorbed and deposited on endothelial cells (ECs) and diet-induced anti-Neu5Gc antibodies (Abs) develop early in human life. While the interaction of Neu5Gc and diet-induced anti-Neu5Gc Abs occurs in all normal individuals, endothelium activation by elicited anti-Neu5Gc Abs following a challenge with animal-derived materials, such as following xenotransplantation, had been postulated. Ten primary human EC preparations were cultured with affinity-purified anti-Neu5Gc Abs from human sera obtained before or after exposure to Neu5Gc-glycosylated rabbit IgGs (elicited Abs). RNAs of each EC preparation stimulated in various conditions by purified Abs were exhaustively sequenced. EC transcriptomic patterns induced by elicited anti-Neu5Gc Abs, compared with pre-existing ones, were analyzed. qPCR, cytokines/chemokines release, and apoptosis were tested on some EC preparations. The data showed that anti-Neu5Gc Abs induced 967 differentially expressed (DE) genes. Most DE genes are shared following EC activation by pre-existing or anti-human T-cell globulin (ATG)-elicited anti-Neu5Gc Abs. Compared with pre-existing anti-Neu5Gc Abs, which are normal component of ECs environment, elicited anti-Neu5Gc Abs down-regulated 66 genes, including master genes of EC function. Furthermore, elicited anti-Neu5Gc Abs combined with complement-containing serum down-regulated most transcripts mobilized by serum alone. Both types of anti-Neu5Gc Abs-induced a dose- and complement-dependent release of selected cytokines and chemokines. Altogether, these data show that, compared with pre-existing anti-Neu5Gc Abs, ATG-elicited anti-Neu5Gc Abs specifically modulate genes related to cytokine responses, MAPkinase cascades, chemotaxis, and integrins and do not skew the EC transcriptome toward a pro-inflammatory profile in vitro.

Immunoglobulin heavy chain can be amyloidogenic: morphologic characterization including immunoelectron microscopy.

It is not well recognized that monoclonal immunoglobulin heavy chains or their fragments can be amyloidogenic. Amyloidosis due to heavy chains, referred to as AH amyloidosis, is rare with only three cases previously reported. An additional case of AH amyloidosis is reported. To the best of our knowledge, this is the first case of IgM heavy chain amyloidosis. A 59-year-old man presented with nephrotic syndrome. Immunoelectrophoresis detected a monoclonal IgM lambda in his serum and free lambda light chains in his urine. A renal biopsy showed amyloidosis, in which the amyloid deposits stained only for mu heavy chain by immunofluorescent and immunoelectron microscopic studies. This case suggests that monoclonal immunoglobulin heavy chains can be amyloidogenic. Furthermore, this type of amyloidosis shares the same morphologic features with other types of amyloidosis and can involve the kidney to produce nephrotic syndrome.