Which bacterial, viral, or parasitic infections can cause a positive anti‑double‑stranded DNA (anti‑dsDNA) antibody test?

Infections Associated with Positive Anti-dsDNA Antibodies

While anti-dsDNA antibodies are highly specific for systemic lupus erythematosus, certain bacterial, viral, and parasitic infections can cause false-positive results, though these are typically lower-titer and transient compared to SLE-associated antibodies.

Bacterial Infections

Tuberculosis

• Tuberculosis can produce positive anti-dsDNA antibodies, occasionally reaching strong positive levels (>800 IU/ml) 1
• These antibodies are typically transient and resolve with treatment of the underlying infection 1

Osteomyelitis

• Bacterial osteomyelitis has been documented to cause positive anti-dsDNA testing, including strong positive results in some cases 1

Syphilis

• Syphilis can cause cross-reactive antibodies that may interfere with certain serologic tests, though specific anti-dsDNA positivity is less well-documented 2

Viral Infections

Epstein-Barr Virus (EBV)

• EBV infection and infectious mononucleosis can produce antibodies that cross-react in anti-dsDNA assays 2
• These are typically seen during acute infection and resolve with viral clearance 2

Cytomegalovirus (CMV)

• CMV infection can cause positive anti-dsDNA results, particularly in immunocompromised patients 2, 3
• CMV antigenaemia should be tested when evaluating patients with suspected lupus who are on high-dose corticosteroids, as CMV can mimic active lupus 3

Polyomavirus BK

• Experimental evidence demonstrates that polyomavirus BK can induce anti-dsDNA antibodies 4
• In normal mice, BK virus produces transient antibodies that bind preferentially to viral dsDNA but do not react in the Crithidia luciliae assay 4
• In lupus-prone mice, BK virus induces persistent, pathogenic anti-dsDNA antibodies similar to those in SLE 4

Hepatitis Viruses

• Hepatitis A, B, and C viruses can cause positive anti-dsDNA results, particularly when patients have predominantly systemic manifestations 2
• Hepatitis B and C should be screened before initiating immunosuppressive therapy 2, 3

HIV

• HIV infection has been associated with positive anti-dsDNA antibodies 2

Parvovirus B19

• Parvovirus B19 infection can produce transient anti-dsDNA positivity 2

Parasitic Infections

Toxoplasmosis

• Toxoplasmosis has been documented as a cause of positive anti-dsDNA antibodies 2
• This typically occurs during active infection with systemic manifestations 2

Critical Distinguishing Features

Infection-Associated vs. SLE-Associated Anti-dsDNA

Titer levels: Infection-associated anti-dsDNA antibodies are typically lower-titer (<800 IU/ml) compared to SLE, though exceptions exist 1

Duration: Infection-related antibodies are transient and resolve with treatment of the underlying infection, whereas SLE-associated antibodies persist 1, 4

Crithidia luciliae reactivity: Infection-induced antibodies often do not react strongly in the Crithidia luciliae immunofluorescence test (CLIFT), which has 98-100% specificity for SLE 5, 6, 4

Clinical context: The presence of clinical criteria for SLE (renal disease, polyserositis, cytopenias, mucocutaneous lesions) strongly favors true SLE over infection-related false positivity 1, 7

Diagnostic Algorithm for Positive Anti-dsDNA

When anti-dsDNA is positive, use a double-screening strategy: First-line solid-phase assay (ELISA/FEIA) followed by confirmatory CLIFT 5, 6

If both SPA and CLIFT are positive: SLE is very likely, and infection is an unlikely cause 5, 6

If SPA is positive but CLIFT is negative: Consider infection, other rheumatologic diseases, or malignancy as alternative explanations 5, 6, 1

Screen for active infections: Test for tuberculosis, HIV, hepatitis B and C, EBV, CMV, and consider parasitic infections based on exposure history 2, 3

Assess complement levels: Low C3 and C4 with elevated anti-dsDNA strongly suggests active SLE rather than infection 3, 7

Monitor antibody levels: Repeat testing after treating suspected infection; persistent elevation favors SLE over transient infection-related antibodies 1, 8

Common Pitfalls

• Do not diagnose SLE based solely on positive anti-dsDNA without clinical criteria, as 41.5% of positive anti-dsDNA results in one study were due to non-SLE causes 1
• Avoid using only one detection method, as combining two quantitative methods (e.g., RIA + CLIA) in patients with homogeneous or speckled ANA patterns maximizes specificity to 100% 9
• Do not ignore the ANA pattern: Anti-dsDNA positivity has highest predictive value (82%) when associated with homogeneous ANA staining 9
• Remember that infection-related antibodies typically lack high avidity, whereas high-avidity anti-dsDNA antibodies by ELISA are most closely associated with true SLE disease activity 7