It is possible to have Lupus with a negative ANA. It is called ANA-Negative Lupus. 95-98% of persons with lupus have a positive test for ANA. Therefore, less than 5% of people can have a negative ANA test, and still have lupus. Therefore, persons having symptoms and signs suggestive of lupus, but with a negative ANA test, should be very carefully evaluated for a large number of conditions that can also have a positive ANA test. These conditions, which can mimic lupus and have a positive ANA test, include mixed connective tissue disease, undifferentiated connective tissue disease, scleroderma, myositis, rheumatoid arthritis and several others. Most of the time, it may take quite a while before a clear diagnosis of Lupus can be made, because evolution of the disease may take some time: symptoms come and go, symptoms develop slowly, some symptoms disappear to be replaced by different symptoms. Such is the nature of the disease. Lupus can present itself in a bewildering number of ways, even to the extent of mimicking other diseases such as RA and MS. With the variety of presentations, lupus is difficult to diagnose and it can be overlooked, often for years, unless the doctor or consultant is alert to its possibility.
Most Lupus patients who have a negative ANA test usually have a positive test for anti-Ro (also called anti-SSA) or anti-La (anti-SSB). Anti-Ro (SSA) is commonly found in cases of ANA-negative lupus and may also indicate Sjogren's Syndrome as an overlap condition (secondary Sjogren's Syndrome) with Lupus. Anti-La(SSB) occurs mainly with primary Sjögren's Syndrome.
About 10% of ANA-Negative Lupus cases may eventually become ANA positive. The features that unequivocally diagnose SLE are (1) high titer anti-double stranded DNA antibody, (2) anti-Sm (Smith) antibody, (3) biopsy-proven kidney disease, or (4) biopsy-proven skin disease, according to The American College of Rheumatology criteria are used to group similar patients together for research and treatment trials. They are classification criteria and are not meant to be used to make a diagnosis. The antibody tests must be accompanied by symptoms, since antibodies alone, with no symptoms, do not diagnose the disease. If a patient has symptoms plus diagnostic antibodies or biopsy proof of disease, the patient has SLE. If the patient lacks all four, the diagnosis is presumptive, even in the presence of illness.
Now, to give you an even more specific answer to your question: The antinuclear antibody test is performed with different techniques in different laboratories; some techniques are more sensitive than others, such that one laboratory may find a (usually weak) positive test while another finds it negative. Some laboratories dilute 10-fold for screening (1:10), some as much as 100-fold (1:100), and some not at all. A commonly used method starts with a dilution of 1:10, then doubles with every successive dilution, so the next specimen tested is 1:20, then 1:40, 1:80, etc., the highest number positive being what the laboratory reports (for instance, 1:1280). Most lupus patients have sera that react at very high dilutions, essentially always more than 1:80, often more than 1:5120. Depending on the laboratory's reporting habits, a test that is positive at 1:10 or even 1:40 may be called either negative or weakly positive. Most laboratories count 1:80 and higher as clearly positive.
The point is that ANA-negative DOES NOT ALWAYS precisely mean COMPLETELY negative. Another point is that speckled (as opposed to diffuse or peripheral) ANA patterns do not read well in automated immunofluorescence tests, so results may be reported as lower titer or negative than they would be if they were hand read by an experienced technician.
The ANA is used to screen for lupus, NOT TO DIAGNOSE IT. This means that, for practical purposes, if the ANA is negative an no other symptoms are presented, lupus does not exist and no further testing need be done; indeed, some laboratories will not further screen sera that are ANA negative. If the ANA is positive, that means only that lupus is possible and that tests for antibody to double-stranded DNA, Sm (Smith), Ro/SSA (Sjogren's syndrome A), La/SSB (Sjogren's syndrome B), and RNP (ribonucleoprotein) must be performed to determine whether lupus is or is not present. Because of a variety of technical factors, it is possible to have a negative ANA but a positive specific antibody test, though this is very uncommon (about 5% as I mentioned above); for positive (not presumptive) diagnosis, a positive test for a specific antibody is more important than is a negative ANA test. Thus an "ANA-negative" person with strongly positive antibody to Sm would unequivocally have lupus (this has occurred more and more often with patients). Because of this possibility, evaluating a patient for lupus, doctors will usually simultaneously (to save time) tests for ANA, anti-DNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, and anti-RNP, as well as for other abnormalities relative to the patient's specific condition. That is, the doctor does not completely discard the diagnosis if the ANA test is negative.
In a lupus patient-or in a patient with suspect lupus-most tests will change during the course of their disease, the changes can either indicate improving or worsening of symptoms. Furthermore, tests often revert to normal during treatment. So, it is also quite possible, during treatment, that a person's ANA can be negative and that person still have active disease.
The answer to the question, "Does ANA-negative lupus exist?" is technically "yes", with a large number of buts, and ifs, and whens. My favorite answer to that question is: the question is really not that important. It is never critical to say, definitively, that a given patient does or does not have lupus. What is important is to evaluate the current symptoms, to put the symptoms into an overall context that includes blood tests, duration of symptoms, other illnesses, and medications, and to develop a treatment plan based on the total information rather than on a blood test alone.
Peace and Blessings