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Test ID: CTDC Connective Tissue Diseases Cascade, Serum

Reporting Name

Connective Tissue Disease Cascade,S

Useful For

Evaluation of patients with signs and symptoms compatible with connective tissue diseases

Clinical Information

The following diseases are often referred to as connective tissue diseases: rheumatoid arthritis (RA), lupus erythematosus (LE), scleroderma (systemic sclerosis) CREST syndrome (calcinosis, Raynaud phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia), Sjogren syndrome, mixed connective tissue disease (MCTD), and polymyositis. Connective tissue diseases (systemic rheumatic diseases) are characterized by immune-mediated inflammation that involves the joints, skin, and visceral organs. These diseases are also accompanied by antibodies to a host of nuclear and cytoplasmic autoantigens.


The diagnosis of a connective tissue disease is based on clinical signs and symptoms and characteristic radiographic, histopathologic, and serologic findings. Certain connective tissue diseases are characterized by autoantibodies that are highly specific for individual diseases (see table). Connective tissue diseases often present clinically with signs and symptoms that are nonspecific, including constitutional signs (eg, fever, weight loss, fatigue, and arthralgias). Accordingly, consideration of the possibility of a connective tissue disease is common on initial clinical presentation and testing for antibodies to autoantigens associated with connective tissue diseases is often performed early in the evaluation of many patients.(1)


Autoantibodies with High Specificity for Individual Connective Tissue Diseases

Cyclic citrullinated peptide antibodies


dsDNA antibodies


Scl 70 antibodies (topoisomerase 1)


Jo 1 antibodies (histidyl tRNA synthetase)


SSA/Ro and SSB/La antibodies

Sjogren syndrome

RNP antibodies (in isolation)


Sm antibodies


Ribosome P antibodies


Centromere antibodies

CREST syndrome


In this test, -serum is tested initially for the presence of antinuclear antibodies (ANA) and for cyclic citrullinated peptide (CCP) antibodies. The presence of CCP antibodies indicates a strong likelihood of RA.(2) The presence of ANA supports the possibility of a connective tissue disease, and the level of ANA is used to identify sera for second-order testing for antibodies to double-stranded DNA (dsDNA) and the other autoantigens. The decision threshold for performing the second-order tests is based on empirical data derived from testing patients with varying levels of ANA and was chosen to minimize testing when positive results for dsDNA and other antibodies are very unlikely.(3)


The testing algorithm is useful in the initial evaluation of patients and performs best in clinical situations in which the prevalence of disease is low.(4)


Interpretive comments are provided.


See individual unit codes for additional information.

Profile Information

Test ID Reporting Name Available Separately Always Performed
ANA2 Antinuclear Ab, S Yes Yes
CCP Cyclic Citrullinated Peptide Ab, S Yes Yes
IM_01 Interpretation No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CMA Centromere Ab, IgG, S Yes No
CASMT ANA2 Cascade No No
RIB Ribosome P Ab, IgG, S Yes No
ENAE Ab to Extractable Nuclear Ag Eval,S Yes No
ADNAR dsDNA Ab with Reflex, IgG, S Yes No

Testing Algorithm

If antinuclear antibodies are ≥3.0 U, then antibodies to double-stranded DNA (dsDNA), extractable nuclear antigen evaluation, ribosome P, and centromere are performed at an additional charge.


If result from dsDNA test is borderline, then dsDNA antibody by Crithidia IFA will be performed at an additional charge.


See Connective Tissue Disease Cascade (CTDC) in Special Instructions.

Report Available

3 to 4 days

Day(s) Performed

Monday through Saturday

Clinical Reference

1. Kavanaugh A, Tomar R, Reveille J, et al: Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. Arch Pathol Lab Med 2000;124:71-81

2. van Boekel MA, Vossenaar ER, van den Hoogen FH, van Venrooij WJ: Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res 2002;4:87-93

3. Tomar R, Homburger H: Assessment of immunoglobulins and antibodies. In Clinical Immunology Principles and Practice. Second edition. Edited by R Rich, T Fleisher, W Shearer, et al. St. Louis, Mosby-Year Book, 2001, pp 120.1-120.14

4. Homburger HA: Cascade testing for autoantibodies in connective tissue diseases. Mayo Clin Proc 1995;70:183-184

Method Name

Enzyme-Linked Immunosorbent Assay (ELISA)

Specimen Type


Specimen Required


Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 1 mL

Specimen Minimum Volume

0.7 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 21 days
  Frozen  21 days

Reference Values


≤1.0 U (negative)

1.1-2.9 U (weakly positive)

3.0-5.9 U (positive)

≥6.0 U (strongly positive)

Reference values apply to all ages.



<20.0 U (negative)

20.0-39.9 U (weak positive)

40.0-59.9 U (positive)

≥60.0 U (strong positive) 

Reference values apply to all ages.

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information



83516-Centromere (if appropriate)

83516-Ribosome (if appropriate)

86225-ds-DNA Ab with Reflex (if appropriate)

86255-ds-DNA Ab by Crithidia IFA (if appropriate)

86235 x 6-RNP, Sm, SS-B, SS-A, Jo 1, and Scl 70 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CTDC Connective Tissue Disease Cascade,S 95267-1


Result ID Test Result Name Result LOINC Value
ANA2 Antinuclear Ab, S 94875-2
CCP Cyclic Citrullinated Peptide Ab, S 94874-5
IM_01 Interpretation 69048-7
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Behavioral, mml-Cerebrovascular, mml-Epilepsy, mml-Headache, mml-Movement-Disorders, mml-Demyelinating-Diseases, mml-Neuroimmunology, mml-Neuromuscular, mml-Autonomic, mml-Pediatric, mml-Spinal-Cord, mml-Neuro-ophthalmology