Tif1-gamma-antibodyTranscriptional intermediary factor 1 gamma;

TIF1 (p155/140) antibodies (TIF= acronym for "transcriptional intermediary factor 1 gamma") are disease-specific and correlate strongly with malignancy.

TIF1-γ is a protein involved in the inhibition of tumorigenesis and metastasis in various malignancies, including breast cancer. The protein belongs to the TRIM superfamily (TRIM = tripartite motif) and occurs in four subtypes known as TIF1-α (TRIM24), TIF1-β (TRIM28), TIF1-γ (TRIM33) and TIF1-δ (TRIM66). TIF-1γ consists of 1120 amino acids and is encoded by the Trim33 gene.

All subtypes have similar structures, which include an N-terminal TRIM that is a protein-protein and oligomerization interface and contains a ring-B-box-coiled-coil (RBCC) domain, a central TIF1 signature sequence (TSS) domain, and a C-terminal combination plant homeodomain (PHD) and bromodomain. (Since TRIM is a ubiquitin ligase involved in protein modification and the C-terminal chromatin-binding unit performs epigenetic transcriptional regulation, TIF1 may have multifunctional protein properties).

TIF-1γ has been shown to play a role in transcription elongation, DNA repair, cell differentiation, embryonic development and mitosis. At the N-terminus is an RBCC unit containing a RING domain, B-boxes and a coiled-coil domain, all of which are involved in the ubiquitination of Smad4. At the C-terminus is a PHD bromodomain that can interact with histones 3 and 4, while a middle linker region that interacts with activated Smad2 and Smad3 connects the two termini.

The TIF-1γ (p155/140) antibody is detected in 40-75% of cases of paraneoplastic dermatomyositis , in 20-25% of cases of the classic adult form and in around 30% of cases of juvenile dermatomyositis. In tumor-associated dermatomyositis, the clinical symptoms may be due to a cross-reactive immune response directed against tumor-associated antigens on cancer cells as well as against constitutive antigens in skin and muscle tissue. The appearance of neoantigens due to loss of heterozygosity or mutations in TIF1-gamma alleles in malignant cells may lead to autoimmunity and thus promote the production of anti-TIF-1-gamma antibodies that cross-react with corresponding TIF1 antigens in skin and muscle. It is postulated that serum levels of anti-TIF-1-gamma autoantibodies positively correlate with disease activity (Wang WY et al. 2024).

1. Volc-Platzer B (2015) Dermatomyositis update. Dermatology 66:604-610
2. Wang WY et al (2024) Anti-TIF-a-gamma associated dermatomyositis in recurrent triple-negative breast cancer. JDDG 20: 1008-1012