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

Abstract

Anti-transcription intermediary factor 1 (TIF1)-γ autoantibodies are robustly linked with cancer-associated DM in adults. This review aims to give an overview of the physiological context of TIF1-γ and to determine whether there is a pathophysiological link between anti-TIF1-γ autoantibodies and the occurrence of cancer. Detection of anti-TIF1-γ autoantibodies has a high sensitivity and specificity for cancer-associated DM in adults and is therefore useful for both diagnosis and cancer risk stratification. The function of the autoantigen, TIF1-γ, may provide insight into the mechanism behind this association. TIF1-γ is a ubiquitously present protein involved in various biological pathways, including TGF-β signalling. In cancer, it can act either as a tumour suppressor or promoter, depending on the cellular context and cancer stage. Evolving data provide pathophysiological insights, linking anti-TIF1-γ autoantibodies to both the anti-tumour response and to muscle and skin damage. TIF1-γ expression is increased in muscle and skin tissue of patients with DM. Mutations or loss-of-heterozygosity in TIF1-γ alleles in malignant tissue may result in the expression of tumour-specific neo-antigens stimulating autoantibody production. The newly formed autoantibodies are hypothesized to cross-react with antigens in muscle and skin, driving the development of DM. 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.

SCLC, Paraneoplastic Dermatomyositis, Positive Transcription Intermediary Factor 1-γ, and Point Mutation in the Transcription Intermediary Factor 1-γ Coding Gene: A Case Report

“…Hence, it is suggested that the immune response to altered TIF1-g in the tumor cross-reacts with native TIF1-g antigens in muscle and skin tissues, causing MAD. 4 The likely pathogenic mutation found in our case and the anti-TIF1-g reduction in response to treatment provide important evidence for this hypothesis. Furthermore, cross-reactivity is considered to be the mechanism causing neurologic paraneoplastic syndromes.…”

“…3 Patients with MAD express a distinct autoantibody pattern usually negative for dermatomyositis-specific autoantibodies yet positive for anti–transcription intermediary factor 1-γ (TIF1-γ), suggesting anti–TIF1-γ plays a role in MAD development. 4 Nevertheless, the underlying mechanism remains unclear. We present a case of a patient with SCLC, paraneoplastic dermatomyositis, positive anti–TIF1-γ, and a mutation in the TIF1-γ coding gene.…”

Anti-TIF1 gamma-positive IPAF patient developed stage IVB lung squamous carcinoma in 1 year: a case report

“…Transcriptional intermediary factor 1γ (TIF1γ), an E3 ubiquitin ligase family member, plays a crucial role in regulating TGF-β/Smad signaling in different cellular contexts [ 5 , 6 ]. Based on its role in this signaling, studies on TIF1γ performed in the last decade have demonstrated a relationship between decreased TIF1γ and cancer [ 7 , 8 ].…”

Marked Improvement of Anti-TIF1-γ Antibody-Positive Dermatomyositis After Chemoradiotherapy to Relevant Nasopharyngeal Cancer

“… 10 , 16 Thus, detection of anti-TIF1-γ-Ab is useful for both DM diagnosis and confirming cancer. 17 In addition, anti-TIF1-γ-Ab can decrease to a normal level after the cancer is cured along with improvement of DM symptoms. 18 However, its mechanism is not well understood.…”