1. Autoantibodies associated with Rheumatic disease
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2. Immune system makes an abundance of proteins Made by white blood cells
Recognize and combat infectious organisms
In autoimmune diseases, autoantibodies may be the actual pathogenic agents of the disease, the secondary consequence of tissue damage, or the footprints of an etiologic agent.
The determination of circulating autoantibodies can be used for the following clinical information:
Likelihood of an autoimmune disease;
Specific diagnosis;
Clinical subtype;
Disease activity (only possible in a very few cases).

3. ANA Target: “normal” proteins within the nucleus of a cell
Could signal the body to begin attacking itself which can lead to autoimmune diseases
A positive ANA test means autoantibodies are present
By itself, a positive ANA test does not indicate the presence of an autoimmune disease or the need for therapy
Sensitivity and simplicity of an ANA test makes it extremely popular to screen for lupus in particular
Nearly all patients with SLE have a positive ANA test
(sensitivity of 93% to 95% and a specificity of 57%)
11-13% of persons with a positive ANA test have lupus
up to 15% of completely healthy people have a positive ANA test
Positive ANA test does not automatically translate into a diagnosis of
lupus or any autoimmune or connective tissue disease

4. What does a positive ANA reading mean?
Reported in titers and patterns
Positive ANA reading alone dose not indicate an autoimmune disease
In healthy individuals 3~15%
Strongly age-dependent:
↑10~37% over the age of 65
Viral infection
Medications
Cancer

5. Arch Pathol Lab Med 124:71-81, 2000

6. 10% to 15% at a titer of 1:80, and 5% at a titer of 1:160 or greater
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 47, No. 4, August 15, 2002, pp 434–444
25% to 30% of healthy persons have a positive test with a titer of 1:40,
10% to 15% at a titer of 1:80, and 5% at a titer of 1:160 or greater
ANA titer of 1:40 is seen in 25% to 30% of relatives of patients
with rheumatologic disorders

7. Different types of ANAs

8. Anti-DNA Antibodies
Very useful in the diagnosis of SLE and assessment of disease activity
Associated with lupus nephritis
Present at some time in the course of the disease as the levels fluctuate and may be absent at times
Reported in rheumatoid arthritis, Sjögren's syndrome, scleroderma,
drug-induced lupus, Raynaud's phenomenon,
mixed connective tissue disease, discoid lupus, myositis,
chronic active hepatitis, uveitis, Graves’ disease,
anticardiolipin antibody syndrome,
women with silicone breast implants

9. Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 47, No. 5, October 15, 2002, pp 546–555
weighted means (weighted according to numbers of patients assessed) for the use of anti-DNA in diagnosing SLE were 57.3% for sensitivity and 97.4% for specificity
positive likelihood ratios (LR) for anti-DNA antibodies in the diagnosis of SLE are very high

10. Anti-Smith Antiribonucleoprotein Antibodies
Antibodies directed against small nuclear riboprotein
Anti-Smith (anti-Sm):
very useful for confirming the diagnosis of SLE
Sensitivity for diagnosis of lupus ranges from 24% to 30%, and specificity ranges from 96% to 98%
(Arthritis Rheum. 2004, 51: )
Antiribonuclear protein (anti-RNP)
bind to protein containing U1-RNA
coexist with anti-Sm antibodies in many patients with SLE
very useful in diagnosing mixed connective tissue disease
(sensitivity from 71% to 100%, specificity from 84% to 100%)

11. Antiribosomal P Protein Antibodies
High specific for lupus and associated with neuropsychiatric lupus
10% to 20% of patients with SLE
32 consecutive SLE patients
Depression (59.4%), headache (46.9%) and cognitive dysfunction (37.5%)
aRP was positive in seven (21.9%) patients, all of whom had one or more NPSLE syndromes
3) significantly higher mean titers of aRP than patients without these disorders
Clin Rheumatol (2008) 27:1377–1385

12. Sjögren's Syndrome Antibodies
Clin Rheumatol (2006) 25: 341–346
The Sjögren's syndrome A antigen (anti-SSA/Ro) consists of 52- and 60-kDa proteins (called Ro52 and Ro60) complexed with Y1-Y5 RNAs
Should be checked in patients with sicca symptoms
Anti-SSA
50% to 60% of patients with primary Sjögren's syndrome and rarely in healthy persons
Other autoimmune disease: RA, SLE, polymyositis
- 35% to 40% of patients with SLE have anti-SSA antibodies
10~15% of secondary Sjögren's syndrome
Associated with development of extraglandular features

13. Algorithm for the use of antinuclear antibodies (ANAs) in the diagnosis of connective tissue disorders

14. 1997 Update of the 1982 ACR Revised Criteria for Classification of SLE
This classification is based on 11 criteria. For the purpose of identifying patients in clinical studies, a person must have SLE if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation (1).The modifications to criterion number 10 were made in 1997 (2).
Arthritis Rheum 1997;40:1725

15. SLICC† Classification Criteria for SLE
Arthritis Rheumatism 2012;64(8);

16. Rheumatoid Arthritis

17. Rheumatoid factor Directed against the Fc portion of IgG
Most commonly measured RF is IgM
Rheumatoid arthritis
(sensitivity: 50% to 80%, specificity: 85% to 90%)
May be negative in the early stages of rheumatoid arthritis, and positivity increases over time
15% to 20% of patients with rheumatoid arthritis never have RF positivity
2% to 10% of healthy persons are RF positive
Correlation between higher RF concentrations and more-severe disease and poor prognosis
RF in monitoring disease activity is unclear

19. Anti–cyclic citrullinated peptide antibodies
Directed against citrulline residues formed in post-translational modification of arginine
often elevated in patients with rheumatoid arthritis
(sensitivity of 30% to 60% and a specificity of 95% to 98%)
Presence of anti-CCP antibodies in early-phase rheumatoid arthritis
anti-CCP antibodies can appear in the circulation several years before the onset of rheumatoid arthritis
presence of anti-CCP antibodies in early disease is highly predictive for more-rapid radiographic progression of disease
anti-CCP antibodies have significantly more joint damage
DDx with Patients with chronic hepatitis C virus infection sometimes have high titers of RF

20. ACR 1987 classification criteria for RA

22. Systemic Sclerosis

23. Anticentromere antibodies
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 49, No. 3, June 15, 2003, pp 399–412
associated with limited cutaneous systemic sclerosis, previously called CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangectasia)
rarely found in patients with other connective tissue diseases or in healthy persons
highly specific for diagnosing systemic sclerosis
(Sensitivity 31% and Specificity 97%)
very useful in distinguishing patients with limited systemic sclerosis from patients with diffuse systemic sclerosis or with primary Raynaud's phenomenon

24. Anti-Scl-70 Very useful in diagnosing systemic sclerosis
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 49, No. 3, June 15, 2003, pp 399–412
Anti-Scl-70
Very useful in diagnosing systemic sclerosis
20.2 % of patients with systemic sclerosis
highly specific (100%) for diffuse disease
useful in predicting a greater likelihood for the development of diffuse cutaneous involvement and radiographic pulmonary fibrosis with an abnormal pulmonary function test

25. Antiphospholipid Antibodies

27. Antiphospholipid antibodies include antibodies directed against phospholipid-associated proteins
Most common measured: lupus anticoagulant, anticardiolipin antibody
Others: anti-beta 2 glycoprotien1, anti-prothrombin,
the “false-posotive” test for syphilis
aCL and LAC are the only autoantibodies which are used as criteria for the diagnosis of APS, other autoantibodies can also be detected in patients’ plasma, and these also have clear relationship with the clinical manifestations of APS
primary tests for diagnosis of APS include aCL and LAC
if these autoantibodies cannot be found but yet the clinical picture is highly suggestive of APS, other autoantibodies should be searched for, such as anti-b2GPI and other aPL.

28. Lupus anti-Coagulant (LAC)
inhibit phospholipids-dependent coagulation tests in vitro
surprisingly are associated with increased risk for coagulation and formation of thrombosis
Anti-Cardiolipin Autoantibodies (aCL)
most frequently used for the diagnosis of APS
the IgG isotype is the most frequent found
very sensitive test for diagnosis of the syndrome
(Since aCL is found in 80%–90% of patients having APS)
signifies an increased risk for venous thrombosis, arterial thrombosis and myocardial infarction
Anti-b2-Glycoprotein-I (b2GPI) Antibodies
serum protein which binds to negatively charged molecules, including phospholipids
aCL actually binds to b2GPI which is linked to cardiolipin
found in 40%–90% of APS patients

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