Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in dermatomyositis patients with anti-TIF1γ autoantibodies
Authors: Hosono Yuji , Sie Brandon , Pinal-Fernandez Iago , Pak Katherine , Mecoli Christopher A. , Casal-Dominguez Maria , Warner Blake M. , Kaplan Mariana J. , Albayda Jemima , Danoff Sonye K. , Lloyd Thomas E. , Paik Julie , Tiniakou Eleni , Milisenda Jose C. , Grau-Junyent Josep M. , Selva-O’Callaghan Albert , Christopher-Stine Lisa , Larman H. Benjamin , Mammen Andrew L. 
Published: March 2022

Objectives

In dermatomyositis (DM), different autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with a substantially increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies.

Methods

Phage ImmunoPrecipitation Sequencing using sera from 67 DM patients suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins myositis patients (255 with DM, 28 with antisynthetase syndrome [ASyS], 40 with immune-mediated necrotizing myopathy [IMNM], 29 with inclusion body myositis [IBM], and 19 with polymyositis [PM]), 75 rheumatologic disease controls (25 with Sjogren’s syndrome, 25 with systemic lupus erythematosus, and 25 with rheumatoid arthritis), and 200 healthy comparators were screened for anti-SP4 autoantibodies by an enzyme-linked immune absorption assay. Serum from 23 Spanish TIF1γ-positive DM patients was also screened for anti-Sp4 autoantibodies

Results

Anti-Sp4 autoantibodies were present in 11.4% of DM and 8% of rheumatoid arthritis patients but not in any other clinical group. Among DM patients, 90% of anti-Sp4 autoantibodies were detected in patients with anti-TIF1γ autoantibodies. Among anti-TIF1γ-positive DM patients from Johns Hopkins and Spain, those with coexisting anti-Sp4 autoantibodies had a decreased risk of cancer (0% vs. 31%; p=0.001, Chi-squared test).

Conclusions

Anti-Sp4 autoantibodies are enriched in anti-TIF1γ-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.

KEY MESSAGES

What is already known about this subject?

Dermatomyositis patients with anti-TIF1γ autoantibodies have an increased risk of cancer.

What does this study add?

Anti-Sp4 autoantibodies are enriched in dermatomyositis patients with anti-TIF1γ autoantibodies.

Anti-Sp4 autoantibodies are only found in dermatomyositis patients without cancer.

Muscle strength is greater in dermatomyositis patients with anti-Sp4 autoantibodies.

Anti-Sp4 autoantibodies are not present in patients with antisynthetase syndrome, immune-mediated necrotizing myopathy, or inclusion body myositis.

Autoantibodies against Sp4 are absent in those with systemic lupus erythematosus or Sjogren’s syndrome and present in 8% of those with rheumatoid arthritis.

How might this impact on clinical practice?

Testing for anti-Sp4 autoantibodies may define a population of anti-TIF1γ-positive dermatomyositis patients without a substantially increased risk of cancer.