It's the big old rim on the .22 LR that makes it so unreliable in a stick-mag fed autoloader.
Most people say the .25 is more reliable than a .22 due to the centerfire design than anything else. Rimfire ammo just isn't the most reliable stuff going and it's a big reason I would never choose a .22 for SD when I can get calibers from a .380 to a .44 mag just by opening my safe door. I don't own small .22 pistols but the .22 autos I have shot and borrowed for a while from friends have all been reliable. They're just as reliable as the ammo is anyway. If I did want to use a .22 of any kind for SD I think I'd get a revolver. I've thought about getting one for my wife even though I don't like the idea of using a .22 for SD. If that's the biggest caliber gun she can handle that's also small enough to carry in a purse then it may be the best choice for her. I got her the .380 but it's hard for her to hang on to due to it's small size and the recoil of it. She doesn't have strong hands but don't tell her I said that. A .22 revolver can work pretty well. I've seen very good examples of small revolvers in fact. The Ruger LCR is a good choice IMO. I'd pick that over giving her my Raven .25 to carry. I wouldn't even consider that. And my P-25 was made in the original factory before it burned down (the old factory made much better pistols).