Antihistone Antibodies (Drug-induced Lupus Antibodies) (012518)

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Turnaround Time: 2 - 5 days
CPT Code:


Test Type: 1 mL Serum
Stability Time:



Room temperature

14 days


14 days


14 days

Reference Range:


• Negative: <1.0 units

• Weak positive: 1.0−1.5 units

• Moderate positive: 1.6−2.5 units

• Strong positive: >2.5 units


Histones are lysine-rich and arginine-rich basic proteins of eukaryotic cells which are predominantly found as complexes with DNA. Antibodies to histones are detected in approximately 30% to 60% of patients with systemic lupus erythematosus (SLE), but their presence in about 95% of patients with drug-induced lupus is more important diagnostically. Drug-induced lupus (primarily caused by procainamide and hydralazine) is clinically similar to SLE, except that the former patients do not have kidney or central nervous system involvement and they do not demonstrate the multiple types of antinuclear antibodies (ANAs) often found in SLE patients. In addition, drug-induced antihistone antibodies react strongly with H2a/H2b fragments (in procainamide-induced SLE) as well as H3 and H4 (in hydralazine-induced SLE). In patients with drug-induced lupus, antihistone antibodies are usually the only ANAs, although antibodies to denaturated DNA have been detected in a small percentage of patients. Antihistone antibodies also occur in approximately 20% of patients with rheumatoid arthritis.

The expected value in the normal population is negative; however, apparently healthy individuals may contain ANA in their sera. This percentage increases with aging, particularly in the seventh decade of life. Certain therapeutic drug regimens and viral syndromes may also cause ANAs.

Biundo JJ, Cummings NA. Biochemical, hematologic and immunologic tests. In: Katz AW, ed. Rheumatic Disease, Diagnosis and Management. Philadelphia, Pa: JB Lippincott;1977:265.

Centers for Disease Control and Prevention. National Institutes of Health.Biosafety in Microbiological and Biomedical Laboratories. 5th ed. Atlanta, Ga:CDC; 2007.

Epstein A, Barland P. The diagnostic value of antihistone antibodies in drug-induced lupus erythematosus. Arthritis Rheum. 1985 Feb; 28(2):158-162. PubMed 3882094

Fritzler MJ, Tan EM. Antibodies to histones in drug-induced and idiopathic lupus erythematosus. J Clin Invest. 1978 Sep; 62(3):560-567. PubMed 357449

Gockel S, Binder WL. Immunoglobulin class specificity of antihistone. Arthritis Rheum. 1985; 25:558.

Klajman A, Kafri B, Shohat T, Drucker I, Moalem T, Jaretzky A. The prevalence of antibodies to histones induced by procainamide in old people, in cancer patients, and in rheumatoid-like disease. Clin Immunol Immunopathol. 1983 Apr; 27(1):1-8. PubMed 6603311

Krippner H, Springer B, Merle S, Pirlet K. Antibodies to histones of the IgG and IgM class in systemic lupus erythematosus. Clin Exp Immunol. 1984 Oct; 58(1):49-56. PubMed 6332696

Portanova JP, Rubin RL, Joslin FG, Agnello VD, Tan EM. Reactivity of anti-histone antibodies induced by procainamide and hydralazine. Clin Immunol Immunopathol. 1982 Oct; 25(1):67-79. PubMed 6983942

Rubin RL, Joslin FG, Tan EM. Specificity of antihistone antibodies in systemic lupus erythematosus. Arthritis Rheum. 1982 Jul; 25(7):779-782. PubMed 6980652

Collection Details:

Collection Instructions:

Red-top tube or gel-barrier tube.

Maintain specimen at room temperature.