Assuming lab accuracy, what are some of the hallmarks and symptoms that would lead to a diagnosis of ANA-negative lupus as opposed to any other autoimmune condition?

I would not make an initial diagnosis of ANA-negative systemic lupus erythematosus (SLE) lightly, especially since there are so many mimics of SLE. However, it does occur, even in early, untreated patients. Even some of the best lupus centers in the world (SLICC) have a 6% prevalence of ANA-negative...

Since SLICC and 1997 ACR criteria better capture ANA negative Lupus- I will use these criteria if my suspicion of Lupus is high and ANA is negative.

Dr. @Dr. First Last created a nice summary of ANA- SLE.

I would just add, that SLE should not be diagnosed if the patient never had a positive ANA, at 1/80 or greater dilution. ANA often turns negative with effective treatment. IF ANA is most sensitive and most appropriate for screening.