What a great book. The title, as has been widely explained, comes from a Mark Twain epigraph:
When a true genius appears in the world, you may know him by this sign, that the dunces are all in confederacy against him.
I think the reading from this epigraph suggests that we are supposed to imagine that Ignatius Reilly is a “true genius.” Indeed all the dunces are arrayed in confederacy against him. Of course, the central irony of the book is that Reilly is himself a great dunce, perhaps the greatest of them all.