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HelpTest Code CTDC Connective Tissue Diseases Cascade, Serum
Reporting Name
Connective Tissue Disease Cascade,SUseful For
Evaluation of patients with signs and symptoms compatible with connective tissue diseases
Initial evaluation of patients in clinical situations in which the prevalence of disease is low (6)
This test is not recommended for:
-Testing in clinical situations in which there is a high prevalence of connective tissue diseases (eg, rheumatology specialty practice)
-Follow-up evaluation of patients with known connective tissue diseases
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 |
| ADNA1 | dsDNA Ab, IgG, S | Yes | No |
Testing Algorithm
If antinuclear antibodies are greater than or equal to 3.0 U, then antibodies to double-stranded DNA (dsDNA), extractable nuclear antigen evaluation, ribosome P, and centromere are performed at an additional charge.
For more information see Connective Tissue Disease Cascade.
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
SerumSpecimen Required
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Information: Centrifuge and aliquot serum into plastic vial.
Specimen Minimum Volume
0.7 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 21 days | |
| Frozen | 21 days |
Special Instructions
Reference Values
ANTINUCLEAR ANTIBODIES (ANA)
≤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.
CYCLIC CITRULLINATED PEPTIDE ANTIBODIES, IgG
<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.
Day(s) Performed
Monday through Saturday
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
86038
86200
83516-Centromere (if appropriate)
83516-Ribosome (if appropriate)
86225-ds-DNA AB IgG, Serum (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 | 33935-8 |
| IM_01 | Interpretation | 69048-7 |
Clinical Information
The following diseases are often referred to as connective tissue diseases (CTD): rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis including CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia), Sjogren syndrome, mixed connective tissue disease, and idiopathic inflammatory myopathies. CTD (also known as 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 any CTD is based on clinical signs and symptoms and characteristic radiographic, histopathologic, and serologic findings. Certain CTD are characterized by autoantibodies that are highly specific for individual diseases as outlined in the Table. CTD often present clinically with signs and symptoms that are nonspecific, including constitutional signs such as fever, weight loss, fatigue, and arthralgias.
Table. Autoantibodies and Clinical Associations with Specific Connective Tissue Diseases
|
Cyclic citrullinated peptide antibodies |
Rheumatoid arthritis |
|
Double-Stranded DNA (dsDNA) |
Systemic lupus erythematosus (SLE) |
|
Smith (Sm) |
SLE |
|
Ribosome P |
SLE |
|
SS-B/La |
Sjogren syndrome (SjS) |
|
SS-A/Ro (Ro52 or Ro60) |
SjS, SLE, systemic sclerosis (SSc), antisynthetase syndrome |
|
RNP 68 and A (RNP) |
Mixed connective tissue disease |
|
Topoisomerase 1 (topo-1, Scl-70) |
SSc |
|
Histidyl tRNA synthetase (JO1) |
Idiopathic inflammatory myositis (commonly anti-synthetase syndrome) |
|
Centromere B |
SSc (most commonly the limited cutaneous forms: LcSSc) |
In this testing cascade, 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 rheumatoid arthritis (RA).(1) However, additional testing for rheumatoid factor, which is not included in the cascade, is important for optimal diagnosis as per the 2010 American College of Rheumatology/European League Against Rheumatism RA classification criteria.(2) The presence of ANA supports the possibility of a CTD, and the level of ANA is used to identify sera for second-order testing for antibodies to dsDNA and the other autoantigens. The decision threshold for performing second-order tests is based on empirical data derived from testing patients with varying levels of ANA and is chosen to minimize testing in situations in which positive results for dsDNA and other antibodies is very unlikely.(3) However, a negative ANA enzyme immunoassay result does not rule out a diagnosis of CTD as has been reported in a number of studies. Therefore, in patients with a strong clinical suspicion of CTD, testing for ANA by indirect immunofluorescence assay may be warranted.(4,5)
Interpretation
Interpretive comments are provided.
See individual test IDs for additional information.
Differential testing for Ro52 and Ro60 antibodies in SS-A/Ro positive patients may be useful in the diagnosis of specific CTD clinical subset, disease stratification, and prognosis. Consider testing for Ro52 and Ro60 antibodies (ROPAN / Ro52 and Ro60 Antibodies, IgG, Serum) if the patient is positive for SS-A/Ro.
Report Available
3 to 4 daysSpecimen Retention Time
14 daysReject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | OK |
Method Name
Enzyme-Linked Immunosorbent Assay (ELISA)