A positive ANA is significant only in the presence of clinically relevant symptoms. A high titre ANA can occasionally be present in normal individuals, particularly with increasing age, and under those conditions may be of no significance. An ANA may also be associated with the use of certain classes of drugs. If the ANA is considered to be clinically relevant, investigations as outlined below may be helpful in disease classification and assessment of activity

In those who have a high titre ANA with no relevant symptomatology, occassional clinical and serological review may be useful, as it is possible for the antibody to appear well before disease symptoms.

Additional Investigations for Positive ANA:

1. Antibodies to double stranded DNA:

• if positive highly suggestive of SLE
• if negative does not exclude SLE
• variation in level related to disease activity.

2. Antibodies to ENA:

• Sm if present, highly specific for SLE
• SSA can rarely be seen in ANA negative SLE
• SSA and/or SSB are associated with Sjogren's Syndrome
• RNP in high titre isassociated with mixed connective tissue disease.
• Jo-1 is associated with interstitial lung disease of varying aetiologies
• SCL-70 is strongly associated with the diffuse scleroderma

3. Rheumatoid factor:

Most frequently present in RA or Sjogren's Syndrome, in the latter often in combination with ANA and anti SSA and/or SSB.

5. Centromere pattern of ANA:

Highly associated with the limited (CREST) variant of scleroderma.

These antibodies mark a group of patients particularly predisposed to arterial or venous thromboembolic phenomena and recurrent miscarriages. A large proportion have SLE but in many this antibody is present without SLE or an associated ANA. In SLE its presence is also associated with CNS disease and thrombocytopenia. It is worthwhile screening for these antibodies in patients with SLE and in anyone with recurrent arterial or venous thromboembolic phenomena or recurrent miscarriages.

7. C3 and C4:

These are depressed in active SLE and rise with disease remission

8. Acute phase reactants (alpha 1 antitrypsin, fibrinogen, haptoglobin, CRP)

Elevated in active connective tissue diseases and fall with remission. These will sometime be elevated in the presence of a normal ESR.

9.Immunoglobulin levels

Tend to be elevated in the presence of inflammatory diseases