Autoantibodies in Connective Tissue Disease
Antibody
Associated Disease
Interpretation
Indication to order
Testing Technique
DS DNA = nDNA
-High level (>2-3 std dev, 1:320) confirms clinical
dx of SLE
-Low level in RA, Hashimoto, Graves,
Waldenstrom, MCTD, SSc, AI liver dx, SS
-Low diagnostic value
-Increased in childhood linear morphea
-+ in many CTDs
-+ in only 50-80% of SLE
-assoc with renal dz in SLE
- high value = specific for SLE
-Question of SLE
- + in normal people
- want > 3 std dev to be significant
- Rarely
-indirect IF: uses crithidiae mitochondria which only
has dsDNA (so + or – only)
- elisa: uses calf thymus, increased sensitivity, gives a
value
- elisa: check by anti-DNA ab that is further extracted
to SSDNA from calf thymus
- Drug induced SLE (90%+)
- SLE (30%+)
-SS
-SLE
-SCLE (70-90%)
- Increased with vasculitis
- Drug induced SCLE*
-same as RO, but incidence 50% less
-MCTD (100% by definition)
-SLE (30%)
-Rarely neonatal LE, SS
-SLE (very specific/diagnostic)
-Only 15-40% + in SLE
- cannot exclude idiopathic SLE if +
- if suspect drug induced SLE
- correlates with photosensitivity in
SCLE
- incidence varies with testing
technique
-w/u for photo-sensitivity
-suspicion of neonatal LE, SS
-suspicion of SCLE or SLE with
negative ANA
-IF: uses animal substrate like liver
- elisa: uses commercial histone complement fixation
-Radial imunodiffusion: high spec, low sens (must
contain lg amt to be +, so + = high diagnostic value)
-Elisa: low spec, high sens (+ = low diagnostic value
unless 2-3 std dev, but gives quantitative value)
-90% of pts with +LA have +RO
-is to exclusion of other abs in MCTD
-majority have SLE b/c SLE > MCTD
-same as RO
-attempting to confirm MCTD or SLE
-same as RO
-same as RO
-confirms SLE
-+ SM = + U1RNP
-+U1RNP not = + SM
-marker for worse dz (compared to
just CREST)
-specific for SSc
- only 2% SSc have positve
-associated with pulmonary sxs in
SLE
-attempting to confirm SLE
-same as RO
SS DNA
Histones
Anti- RO, SSA
Anti-LA, SSB
U1RNP
Anti-SM
SCL 70
(aka anti-topoisomerase)
Anti-centromere
JO-1
(aka anti-histidyltRNA synthase)
-SSc (incidence 10-20%)
CREST (50-90% positive)
-Dermatomyositis, polymyositis
-SLE
-to distinguish bad SSc from less bad
Suspect CREST
nDNA, native DNA; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; MCTD, mixed connective tissue disease; SSc, systemic sclerosis (scleroderma); AI, autoimmune; SS, sjogren’s syndrome; IF,
immunofluorescence;
*drugs assoc = hydrochlorothiazide, ACE inhibitors, Ca channel blockers, interferons, statins (Archives of Dermatology Jan 2003)
taken mainly from JAAD Nov 2000, CME
ANA Patterns and their Antigens and Disease Associations
ANA
Predominant antigen
Disease
Peripheral
Homogenous
Nucleolar
Centromere
Speckled
nDNA
nDNA, histones
Nucleolar RNA
Kinetochore
Various ribonucleic proteins
SLE
SLE
SSC, SLE
CREST
SLE, SSc, SS
Positive ANA in a healthy population
Conditions other than CTDs with positive ANA
Titer
1:40
1:80
1:160
1:320
Elderly persons
Pregnancy
Relatives of patients with CTD
Other autoimmune disease (autoimmune thyroiditis, pimary biliary cirrhosis)
Chronic infections
Prevalence
32%
13%
5%
3%
Neoplasms
Medications (procainamide, hydralazine)
Normal healthy individual