What is the clinical use of histone antibodies?

Clinical Use of Anti-Histone Antibodies

Anti-histone antibodies are primarily used to help diagnose drug-induced lupus erythematosus and to monitor disease activity in patients with lupus nephritis who remain anti-dsDNA negative. 1

Primary Clinical Applications

1. Drug-Induced Lupus Erythematosus (DILE)

• Anti-histone antibodies have traditionally been considered a hallmark of drug-induced lupus, particularly with medications such as:
  • Procainamide
  • Quinidine
  • Isoniazid
  • Sulfasalazine
  • Acebutolol 2

2. Monitoring Lupus Nephritis

• Anti-histone antibodies (H1, H2A, H2B, H3, and H4) are more prevalent in patients with lupus nephritis than in patients without kidney disease 1
• They can be used to monitor disease activity in patients with lupus nephritis who remain anti-dsDNA negative 1
• Important caveat: Should only be used when lupus nephritis is confirmed to be not secondary to any drug treatment 1

Diagnostic Value in SLE

• Anti-histone antibodies are present in approximately 52.4% of SLE patients 3
• They correlate with disease activity:
  • 87% of patients with active SLE show histone antibody positivity
  • Only 18% of patients with inactive SLE are positive 3
• They appear during or just before the onset of an active phase and tend to be absent during remission 3

Laboratory Testing Considerations

• Anti-histone antibodies are heterogeneous, displaying reactivity with one to all five histone classes (H1, H2A, H2B, H3, and H4) 4
• Testing methods include:
  • Solid phase immunoassays
  • Western blot immunoassays 4
  • Immunoenzymatic assays 3

Limitations and Pitfalls

• Anti-histone antibodies are not included in the standard panel of autoantibodies recommended for baseline testing in SLE according to EULAR guidelines 1
• Standard baseline autoantibody testing in SLE should include: ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid, C3, C4 1
• Anti-histone antibody testing has several technical challenges:
  • Results can be affected by degraded or impure histone preparations
  • Irreversible denaturation can affect results
  • The role of soluble histones in biological fluids can interfere with testing 4

Clinical Algorithm for Anti-Histone Antibody Testing

1. Consider testing in suspected drug-induced lupus:

   • Patient on known lupus-inducing medications
   • Development of lupus-like symptoms
   • Absence of other explanatory factors

2. Consider testing in lupus nephritis patients:

   • Confirmed lupus nephritis
   • Negative anti-dsDNA antibodies
   • Need to monitor disease activity
   • No history of drug-induced lupus

3. Interpret results in context:

   • Positive results in patients on lupus-inducing medications suggest DILE
   • Positive results in SLE patients may indicate active disease, particularly nephritis
   • Negative results in previously positive patients may suggest disease remission

In conclusion, while not part of the standard autoantibody panel for SLE diagnosis, anti-histone antibodies have specific clinical utility in diagnosing drug-induced lupus and monitoring disease activity in certain lupus nephritis patients who are anti-dsDNA negative.