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Anti-Nuclear Antibody Tests
Regan Arendse FCP(SA), PhDRheumatologist
Saskatoon
Case study
Questions
• Is the ANA a useful clinical tool?• What causes a false positive ANA?• When should an ANA test be requested?
Rates of positive ANA in healthy and ill
Negative ANAPositive ANAANA with disease
Wandstrat et al., J Autoimmun 2006; 27: 153-60
Gender and positive ANA
Healthy controls (n=18) SLE (n=14)0
10
20
30
40
50
60
70
80
90
100
FemalesMales
Quan-Zhen et al., Arth Res Ther 2011
Age and positive ANA
• No association between age (20-60 years) and ANA positivity
Tan et al., Arth & Rheum 1997; 40: 1601-11
Quan-Zhen et al., Arth Res Ther 2011
Accumulated % + antibodies over 10 years before diagnosis with SLE
-10 -9 -8 -7 -6 -5 -4 -3 -2 -1 diagnosis 0
10
20
30
40
50
60
70
80
90
100
ANAdsDNARNPSSA
Erikson et al., Arth Res Ther 2011; 13
Antibody presence predating disease
arthritis skin serositis other0
1
2
3
4
5
6
7
8
Erikson et al., Arth Res Ther 2011; 13
Predictive value of ANA for SLE
• Incidence rate of SLE, lupus develops in <1% positive ANA individuals
• None of 24 ANA asymptomatic children developed disease over mean 61 month follow up period
• Predictive value of ANA increases in the at risk population with clinical disease
Aho et al., J Rheum 1992; 19: 1377-9
Cabral et al., Pediatrics 1992; 89: 441-4
Answer
• The ANA is not a good screening tool for auto-immune disease in the absence of convincing clinical signs
• Long time interval between ANA positivity and onset of disease does not warrant screening
• Lack of any effective pre-emptive or prophylactic treatment emphasizes that the argument not to routinely request an ANA
What causes a false positive ANA?
HEp-2 indirect immunofluorescence
Antigens with similar structure to pathologic antigens
• Viruses (Herpes viruses and HIV)• Drugs which alter proteins (Procainamide,
INH, Phenytoin)• Malignant cells• Environmental toxins (silicone)
When should an ANA test be requested?
• Yes if strong clinical suspicion of autoimmune disease
• Scleroderma• Lupus• Dermatomyositis• Sjogren’s disease• Mixed connective tissue disease
When should an ANA test be requested?
• No if not a strong clinical suspicion of autoimmune disease
• Chronic pain• Chronic fatigue • Chilblains • Raynaud’s phenomenon• Rosacea
When should an ANA test be requested?
• 8.8% of fibromyalgia patients have +ANA• 8.9% of controls have +ANA• In prospective study over 4 years, in 12 with
FMS and 12 controls, one in FMS group developed SLE and one in controls developed Sjogren’s syndrome
Al Allaf et al., Clin Rheuma 2002; 21: 472-7
Conclusion
• ANA should not be routinely requested• ANA should not be requested for non-specific
symptoms• ANA should only be requested in patients with
clinical features strongly suggestive of an auto-immune disease
• Causes of false positives are many and varied