Autoantibodies in Connective Tissue Disease

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 / -+ in only 50-80% of SLE
-assoc with renal dz in SLE
- high value = specific for SLE / -Question of SLE / -indirect IF: uses crithidiae mitochondria which only has dsDNA (so + or – only)
- elisa: uses calf thymus, increased sensitivity, gives a value
SS DNA / -Low diagnostic value
-Increased in childhood linear morphea
-+ in many CTDs / - + in normal people
- want > 3 std dev to be significant / - Rarely / - elisa: check by anti-DNA ab that is further extracted to SSDNA from calf thymus
Histones / - Drug induced SLE (90%+)
- SLE (30%+) / - cannot exclude idiopathic SLE if + / - if suspect drug induced SLE / -IF: uses animal substrate like liver
- elisa: uses commercial histone complement fixation
Anti- RO, SSA / -SS
-SLE
-SCLE (70-90%)
- Increased with vasculitis
- Drug induced SCLE* / - 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 / -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)
Anti-LA, SSB / -same as RO, but incidence 50% less / -90% of pts with +LA have +RO / -same as RO / -same as RO
U1RNP / -MCTD (100% by definition)
-SLE (30%)
-Rarely neonatal LE, SS / -is to exclusion of other abs in MCTD
-majority have SLE b/c SLE > MCTD / -attempting to confirm MCTD or SLE / -same as RO
Anti-SM / -SLE (very specific/diagnostic)
-Only 15-40% + in SLE / -confirms SLE
-+ SM = + U1RNP
-+U1RNP not = + SM / -attempting to confirm SLE / -same as RO
SCL 70
(aka anti-topo-
isomerase) / -SSc (incidence 10-20%) / -marker for worse dz (compared to just CREST)
-specific for SSc / -to distinguish bad SSc from less bad
Anti-centromere / CREST (50-90% positive) / - only 2% SSc have positve / Suspect CREST
JO-1
(aka anti-histidyl-
tRNA synthase) / -Dermatomyositis, polymyositis
-SLE / -associated with pulmonary sxs in SLE

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 / nDNA / SLE
Homogenous / nDNA, histones / SLE
Nucleolar / Nucleolar RNA / SSC, SLE
Centromere / Kinetochore / CREST
Speckled / Various ribonucleic proteins / SLE, SSc, SS

Positive ANA in a healthy populationConditions other than CTDs with positive ANA

TiterPrevalenceElderly persons

1:4032%Pregnancy

1:8013%Relatives of patients with CTD

1:1605%Other autoimmune disease (autoimmune thyroiditis, pimary biliary cirrhosis)

1:3203%Chronic infections

Neoplasms

Medications (procainamide, hydralazine)

Normal healthy individual