Test Catalog

Test ID: CTDC    
Connective Tissue Diseases Cascade, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

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

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If antinuclear antibodies are > or =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.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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)

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


< or =1.0 U (negative)

1.1-2.9 U (weakly positive)

3.0-5.9 U (positive)

> or =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)

> or =60.0 U (strong positive) 

Reference values apply to all ages.

Interpretation Provides information to assist in interpretation of the test results

Interpretive comments are provided.


See individual unit codes for additional information.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Results must be interpreted in the context of the complete clinical picture.


The presence of detectable levels of antinuclear antibodies (ANA) is not specific for connective tissue disease. False-positive results for ANA occur in approximately 15% of women over age 40.(1) Weakly positive results for cyclic citrullinated peptide antibodies may occur in patients with connective tissue diseases other than rheumatoid arthritis.


This test is not recommended for:

-Testing in clinical situations with a high prevalence of connective tissue diseases (eg, rheumatology specialty practice)

-Follow-up evaluation of patients with known connective tissue diseases

Clinical Reference Recommendations for in-depth reading of a clinical nature

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

Special Instructions Library of PDFs including pertinent information and forms related to the test