ANA are only generated when the body has at some point attacked its own cells... It is (in my opinion) a result of disease, rather than a cause of disease.
It is associated with certain autoimmune conditions (eg Lupus), but also other conditions such as endometriosis, and even certain infections and cancers.
The situation is complicated but i think we know that ANA actually cause disease because maternal ANA cause neonatal lupus. As soon as the newborn has lost the maternal antibody it is healthy.
Speckled ANA can occur in lupus but on its own is more often associated with a range of syndromes that do not include large immune complex disease (which usually manifests as rash, nephritis or cerebritis). The features of speckled ANA syndromes look more like the direct effects of antibody on cell function. Sjogren's is the best documented example, which has a speckled ANA associated with anti-Ro. Mixed connective tissue disease is another one - with a speckled ANA from anti-RNP. But there are probably fifty other antigens that can give speckled ANA.
I would personally think a speckled ANA at 1:160 is very likely showing the cause of illness. It would be good to know what the antigen is but it may not be one of the ones usually tested for in the 'extractable nuclear antigen screen'. What is certainly the case is that speckled ANA is associated with severe fatigue in many situations where we do know the antigen.
One of the reasons why some studies of CFS show nobody has speckled ANA is that this may have excluded patients from being in the study. Some physicians do not diagnose CFS in the presence of ANA. Which is why we need population based studies on raw data that do not prejudge diagnosis before group selection in order to get information on possible causal relations.