Anti-Th/To Antibodies in Scleroderma: Good Prognosis or Serious Concern?

Abstract

Systemic sclerosis (SSc) represents a rare and intricate autoimmune connective tissue disease, the pathophysiology of which has not been fully understood. Its key features include progressive fibrosis of the skin and internal organs, vasculopathy and aberrant immune activation. While various anti-nuclear antibodies can serve as biomarkers for the classification and prognosis of SSc, their direct role in organ dysfunction remains unclear. Anti-Th/To antibodies are present in approximately 5% of SSc patients, and are particularly prevalent among those with the limited subtype of the disease. Although the presence of these autoantibodies is associated with a mild course of the disease, there is a strong connection between them and severe clinical manifestations of SSc, including interstitial lung disease, pulmonary arterial hypertension and gastrointestinal involvement. Also, the additional clinical correlations, particularly with malignancies, need further research. Moreover, the disease's course seems to be influenced by antibodies, specific serum cytokines and TLR signaling pathways. Understanding the relationships between presence of anti-Th/To, its molecular aspects and response to treatment options is crucial for the development of novel, personalized therapeutic techniques and should undergo profound analysis in future studies.

Keywords: RNAse MRP and P; anti-Th/To; autoantibodies; interstitial lung disease; pulmonary arterial hypertension; scleroderma; systemic sclerosis.

Figure 1

Structural features of RNase MRP and P complexes.

Figure 2

The function of RNase MRP in human cells [19]. (A) During ribosome biogenesis, RNase MRP participates in pre-rRNA processing. The cleavage takes place at the A3 site in ITS1 (internal transcribed spacer) and results in 25S, 18S and 5.8S rRNAs. Pre-rRNAs undergo essential folding, processing and modification to produce the pre-40S and pre-60S subunits. Once the last stages of maturation are completed, both subunits are exported to the cytoplasm, where they become ready for translation [20]. (B) RNase MRP generates RNA primers for mitochondrial DNA replication. (C) Viperin is an interferon-induced antiviral protein produced by human cells [21]. One of the functions of RNase MRP is to degrade viperin’s mRNA by cutting it at two cleavage sites [22]. (D) RNase MRP promotes the cell cycle via degradation of cyclin B mRNA, which, in its active form, stimulates the end of mitosis.

Figure 2

The function of RNase MRP in human cells [19]. (A) During ribosome biogenesis, RNase MRP participates in pre-rRNA processing. The cleavage takes place at the A3 site in ITS1 (internal transcribed spacer) and results in 25S, 18S and 5.8S rRNAs. Pre-rRNAs undergo essential folding, processing and modification to produce the pre-40S and pre-60S subunits. Once the last stages of maturation are completed, both subunits are exported to the cytoplasm, where they become ready for translation [20]. (B) RNase MRP generates RNA primers for mitochondrial DNA replication. (C) Viperin is an interferon-induced antiviral protein produced by human cells [21]. One of the functions of RNase MRP is to degrade viperin’s mRNA by cutting it at two cleavage sites [22]. (D) RNase MRP promotes the cell cycle via degradation of cyclin B mRNA, which, in its active form, stimulates the end of mitosis.

Figure 3

The clinical manifestation of anti-Th/To patients.