Clinical Information

Of the systemic lupus erythematosus (SLE)-specific antibodies outlined in the immunology domain of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE,(1) antibodies to double-stranded DNA (dsDNA) is the most common. It is also included in the Systemic Lupus International Collaborating Clinics classification criteria (SLICC) for SLE.(2) Detection of IgG antibodies to dsDNA is the most used isotype clinically.(3-5) The diagnostic performance of dsDNA IgG antibodies in SLE is variable and dependent on several factors; notably the immunological method used for their detection, the structure of the DNA, the patient’s disease state (early or active vs inactive) including specific clinical manifestations and demographics.(3-7) Weak-positive dsDNA IgG antibodies have low affinity and low avidity with variable clinical correlations for SLE.(3)

Testing for IgG antibodies to dsDNA is indicated in patients positive for anti-cellular antibody (ie, antinuclear antibody: ANA) homogeneous pattern using HEp-2 substrate by indirect immunofluorescence assay (IFA) along with clinical features compatible with SLE.(1,2,8). A minority of SLE patients may test negative using HEp-2 by IFA for nuclear antibodies.(8,9) Testing antibodies associated with HEp-2 IFA cytoplasmic pattern such as ribosomal P IgG autoantibodies may be useful if features of neuropsychiatric disease are present. Alternatively, patients may be tested for Smith, ribonucleoprotein, SSA-52, and SSA-60 antibodies.(8,9)

The levels of antibodies to dsDNA may fluctuate with SLE disease activity. Increasing antibody levels may be associated with flares while decline or negative results may indicate response to treatment or disease remission.