Response to Letter by Krischek and Kasuya
We appreciate Dr Krischek and Kasuya’s thoughtful comments regarding our recent article “Genomics of Human Intracranial Aneurysm Wall” published in Stroke.1 Our 2 study centers independently showed the potential critical role of the inflammatory and immune response pathways in aneurysm pathobiology.1,2 We congratulate the authors on their work and innovative approach.
We agree that using the superficial temporal artery has limitations, but it is likely the best current option. Other options have limitations as well. Postmortem tissue has the disadvantage of excessive RNA degradation. Obtaining intracranial vessels during epilepsy or arteriovenous malformation surgery raises questions regarding genetic heterogeneity among different patients and populations. We do, however, acknowledge the value in examining these tissues.
In the study by Dr Krischek et al,2 “pathological” intracranial arteriovenous malformation feeder vessels were used as control. Both the top-scoring networks in their study and our functional annotation pathway analysis demonstrated similar results implicating inflammatory and immune responses. This is interesting and encouraging particularly because different control vessels were used in the 2 studies. This lends further credibility to the hypothesis that inflammation plays a central role in intracranial aneurysm pathobiology. However, whether an antigen-driven immune response is at play needs further analysis. This has been shown to be the case in Kawasaki disease where an oligoclonal IgA immune response exists in the vascular wall.3 Our group recently discovered that an antigen-directed oligoclonal IgG immune response is present within cerebral cavernous malformation lesions.4
In addition to the inflammatory and immune response pathway, our study implicated other pathways which were not noted in the study by Dr Krischek et al.2 This may partially be due to the different microarray platforms used in the 2 studies. The microarray platform used by Dr Krischek et al was an Agilent Human Oligo Microarray which carries 18 716 transcripts of human gene expressions, whereas ours was Illumina Human WG6-v2 Microarray containing 43 148 transcripts of human gene expressions, which covers almost the entire human genome.
The surface has only been scratched regarding the role of inflammation in intracranial aneurysm pathobiology. Further analysis of human aneurysm wall and mechanistic studies in animal models will be needed to further refine our understanding in this area.
Shi C, Awad IA, Jafari N, Lin S, Du P, Hage ZA, Shenkar R, Getch CC, Bredel M, Batjer HH, Bendok BR. Genomics of human intracranial aneurysm wall. Stroke. 2009; 40: 1252–1261.
Rowley AH, Shulman ST, Spike BT, Mask CA, Baker SC. Oligoclonal IgA response in the vascular wall in acute Kawasaki disease. J Immunol. 2001; 166: 1334–1343.
Shi C, Shenkar R, Du H, Duckworth E, Raja H, Batjer HH, Awad IA. Immune response in human cerebral cavernous malformations. Stroke. 2009; 40: 1659–1665.