Reasons for discontinuing Histone Abs:
- The right antigen is not known
- Histone Abs are not specific for any disease
- Diagnosis of drug-induced lupus can be made without histone antibodies
- Positivity for AHA is often misinterpreted.
Details to these points see below. Further arguments are:
- Patient-to-patient variability is very high
- Association with disease activity in lupus or RA is possible but not usable for monitoring
- No association with specific manifestations
- A negative result for IgG antihistone antibodies does not exclude a diagnosis of drug-induced lupus or SLE
1. The right antigen is not known
For drug induced lupus it is said, that antihistone antibodies (AHA) react with all histones, but have a predominant specificity to H1 and H2B. The classical ELISA for AHA is coated with a mixture of all histones. It is not known, whether those are coated as complex or as single proteins or if the proteins are in a natural or denatured conformation.
Some authors claim that antibodies against the (H2A-H2B)-DNA complex are the "real" markers for drug-induced lupus (DIL). But what is the difference of this complex to the nucleosome? Nucleosomal antibodies are said to be highly specific for SLE, not for DIL. The dimer H2A-H2B seems to much less specific and sensitive for DIL. DNA lacks here - but DNA-antibodies are very specific markers for SLE and are an exclusion criterion for DIL.
On the congress in Geneva in February, one lecturer spoke about H1 antibodies being very specific for SLE. But if they are the typical antigen for histone antibodies and these are typical for DIL ¿ than what is the truth?
2. Histone antibodies are not specific for any disease
Histone Abs belong to the most common ANA. In some connective tissue diseases they occur regularly and in a high amount:
- SLE 50-70%
- Active SLE 80%
- Rheumatoid arthritis (RA) 15%
- Juv. chronic arthritis (JCA) 50-70%
- Sjögren`s Syndrome 23%
- Polymyositis/Dermatomyositis 17%
But they occur also often in Felty's syndrome, diffuse cutaneous scleroderma, systemic sclerosis, autoimmune disorders of the liver, some neurological diseases, infections and even in asymptomatic relatives of SLE-patients.
And of course they are found in drug induced lupus, but dependent on which drug the lupus induced, the frequency of histone abs varies:
- Procainamide induced lupus 85-95%
- Quinidine induced lupus 50%
- Hydralazine induced lupus approx 30%
3. Diagnosis of drug-induced lupus is more accurate without measuring histone antibodies
The diagnosis of DIL should base on the following criteria:
- Signs or symptoms of SLE in a patient on lupus-inducing drug therapy
- No multisystem involvement or serious CNS or renal involvement
- Improvement and resolution of symptoms within days to weeks of discontinuing drug therapy
- No dsDNA antibodies (no Sm, RNP, Ro, La)
- No hypercomplementemia
4. Positivity for AHA is often misinterpreted
AHA often are understood as markers for SLE and drug-induced lupus. But because histone Abs can occur in a wide variety of diseases and even in healthy individuals, the positive result is more misleading than helpful.