Challenges in Using Antinuclear Antibodies for SLE Diagnosis Examined

ANA is not always present in patients with systemic lupus erythematosus, which should be taken into consideration when devising an SLE classification criteria.

Due to fluctuations in antinuclear antibodies (ANA), the presence of positive ANA should not be required for clinical diagnosis of systemic lupus erythematosus (SLE), according to research published in Arthritis Care and Research.

Researchers conducted a retrospective study of 301 patients with cutaneous lupus erythematosus (CLE) from the autoimmune dermatology clinic at the University of Pennsylvania. Using this database, the researchers searched for patients with CLE who had clinical information on ANA status and determined whether patients who were ANA negative met American College of Rheumatology (ACR)/SLE International Collaborating Clinics (SLICC) criteria for SLE.  

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The researchers found that 36.9% of patients had negative ANA, whereas 33.3% had ANA that fluctuated between positive and negative. Of the patients with negative ANA, 18% met either the ACR and/or SLICC SLE criteria; 12 patients met ACR criteria only, and 8 patients met both ACR and SLICC criteria. Nearly 45% (44.4%) of those with fluctuating ANA met either ACR and/or SLICC criteria. Using indirect immunofluorescence assay (IIFA), the researchers checked ANA in 24 patients with fluctuating ANA, resulting in 13 patients being switched from positive to negative ANA and 5 of those patients meeting SLE criteria.

Patients who met ACR criteria most frequently presented with photosensitivity, discoid rash, arthritis, malar rash, and oral ulcers (26, 23, 22, 17, and 15 patients, respectively). Those who met SLICC criteria most frequently presented with chronic cutaneous lupus, acute cutaneous lupus, arthritis, low complements, and positive anti-dsDNA (16, 15, 11, 9, and 9 patients, respectively).

More than 84% of those who met either ACR or SLICC criteria presented with the involvement of at least 1 other non-mucocutaneous organ system, including arthritis, leukopenia, renal involvement, serositis, neurologic involvement, or thrombocytopenia.

One study limitation was the retrospective nature of the research. Additionally, the investigators noted that ANA detection for some patients was performed via ELISA instead of IIFA and that multiple laboratories — each utilizing a different titer cutoff for negative results — were used.

“Given the heterogeneous and complex nature of SLE, it is important to create a classification system to help guide physicians in the diagnosis of this potentially devastating disease to avoid delay in treatment,” the researchers wrote. “Our results demonstrate that ANA is not always present in patients with systemic disease. This should be taken into consideration when devising an SLE classification criteria to be used for clinical trials.”


Tarazi M, Gaffney RG, Kushner CJ, Chakka S, Werth VP. Cutaneous lupus erythematosus patients with a negative antinuclear antibody meeting the American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria for systemic lupus erythematosus [published online May 6, 2019]. Arthritis Care Res. doi:10.1002/acr.23916