Immune responses to CCAR1 and other dermatomyositis autoantigens are associated with attenuated cancer emergence

  title={Immune responses to CCAR1 and other dermatomyositis autoantigens are associated with attenuated cancer emergence},
  author={David F Fiorentino and Christopher A. Mecoli and Matthew C. Rosen and Lorinda S. Chung and Lisa Christopher‐Stine and Antony Rosen and Livia Casciola-Rosen},
  journal={The Journal of Clinical Investigation},
BACKGROUND The temporal clustering of a cancer diagnosis with dermatomyositis (DM) onset is strikingly associated with autoantibodies against transcriptional intermediary factor 1-γ (TIF1-γ). Nevertheless, many patients with anti–TIF1-γ antibodies never develop cancer. We investigated whether additional autoantibodies are found in anti–TIF1-γ–positive patients without cancer. METHODS Using a proteomic approach, we defined 10 previously undescribed autoantibody specificities in 5 index anti–TIF1… 
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Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in dermatomyositis patients with anti-TIF1gamma autoantibodies

Anti-SP4 autoantibodies are enriched in anti-TIF1gamma-positive DM patients without cancer, suggesting that the development of an anti-Sp4 immune response may correlate with a relatively low risk of cancer in these patients.

Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies

Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk and are confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein.

Using autoantibody signatures to define cancer risk in dermatomyositis

Findings indicate that more detailed autoantibody phenotyping at diagnosis might better predict cancer risk and also suggest that diversity and kinetics of the host immune response might influence cancer development.


Variations and subclassifications within the same DMSA subtypes are observed: anti-MDA5 dermatomyositis is clinically subcategorized into good, intermediate, and poor prognostic subgroups; concurrent anti-CCAR1 and anti-TIF1-g positivity identify anti- TIF 1-g-positive patient with a lower risk for cancer-associated myositis.

Update on dermatomyositis

DMSA, evidence of prominent IFN1 pathway activation, and risk/severity-associated biomarkers would likely play major roles in future dermatomyositis classification, disease monitoring, and treatment decision.



Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins.

OBJECTIVE To identify the 140-kd autoantigen recognized by anti-155/140 autoantibodies that are associated with adult cancer-associated dermatomyositis (DM) and juvenile DM and to determine the

Strong correlation between cancer progression and anti-transcription intermediary factor 1γ antibodies in dermatomyositis patients.

Not only did anti-TIF1γ antibodies correlate strongly with malignancy in DM patients, but cancers were also significantly more advanced inAnti-Tif1γ-positive DM patients than in anti- TIF1αγ-negative patients and in such cases were very frequently found close to the time of the DM diagnosis.

The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody–positive dermatomyositis

Anti-TIF1-Ab-positive-associated malignancy occurs exclusively within the 3 year period on either side of DM onset, the risk being highest in those ≥39 years of age.

Anti-TIF1-γ autoantibodies: warning lights of a tumour autoantigen.

Based on the current evidence, anti-TIF1-γ autoantibodies should be considered warning lights of a potential tumour autoantigen and should alert the physician to the possibility of an underlying cancer.

Review: Cancer‐Induced Autoimmunity in the Rheumatic Diseases

The autoimmune rheumatic diseases provide an exceptional opportunity to study cancer-immune interactions, and interrogate the mechanisms of the autoimmune r heumatic diseases, as well as the natural immune response to cancers in humans.

A novel autoantibody to a 155-kd protein is associated with dermatomyositis.

A newly recognized autoantibody, anti-p155, is associated with DM and cancer-associated DM, and is one of the most commonAutoantibodies in this condition, occurring as frequently in children as in adults.

Association of the Autoimmune Disease Scleroderma with an Immunologic Response to Cancer

Analysis of peripheral blood lymphocytes and serum suggested that POLR3A mutations triggered cellular immunity and cross-reactive humoral immune responses in patients with scleroderma and provided support for the idea that acquired immunity helps to control naturally occurring cancers.

Distinct dermatomyositis populations are detected with different autoantibody assay platforms.

It is demonstrated that for some specificities, especially anti-TIF1-γ, antibody results obtained using different assay platforms vary, and identify significantly different patient populations, highlighting the need for standard adoption of carefully validated platforms to detect dermatomyositis autoantibodies.

Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ.

These studies demonstrate that anti-NXP-2 and anti-TIF-1γ antibodies are frequent DM specificities and are present in most patients with cancer-associated DM.