Protein Levels in Blood May Help Determine Treatment Intensity in Early Rheumatoid Arthritis

Protein Levels in Blood May Help Determine Treatment Intensity in Early Rheumatoid Arthritis

Single variants in a specific gene and how they correlate with peptide levels in the blood may help predict treatment requirements in early rheumatoid arthritis.

The study, “Vasoactive intestinal peptide gene polymorphisms, associated with its serum levels, predict treatment requirements in early rheumatoid arthritis,” was published in the journal Scientific Reports.

Researchers from Universidad Complutense de Madrid had already observed that patients with early arthritis carrying low levels of vasoactive intestinal peptide (VIP) in their serum — a small protein (peptide) capable of controlling the immune system’s response — were associated with worse clinical outcomes. Lower levels of VIP are detected in several inflammatory and autoimmune diseases and are associated with more severe disease in Chagas cardiomyopathy and juvenile idiopathic arthritis, with clinical evidence of cardiac autonomic neuropathy.

However, using VIP serum levels as a viable biomarker in daily clinical practice presented methodological problems. To overcome this issue, researchers tried to understand whether variations in the DNA sequence of the VIP gene were also associated with protein expression in the blood and whether they could reproduce the prognostic value previously described for VIP serum levels.

The team analyzed the VIP gene sequence of 20 patients with early arthritis carrying either high or low serum VIP levels.

The analysis identified 120 VIP variants distributed between the two groups of patients. Sixteen variants in a single nucleotide (DNA building blocks), commonly known as single nucleotide polymorphisms, or SNPs, differed between high and low VIP patients.

“Our results show that variations of the VIP gene affect its serum levels in early arthritis patients,” researchers wrote.

Two specific variants (rs35643203 and rs12201140) located in two different regions of the VIP gene were associated with a lower concentration of VIP in patients’ serum, while a third variant (rs688136), located at another chromosomic region, was associated with increased VIP serum levels.

Moreover, researchers analyzed treatment intensity according to the different variants’ load in each patient and found that those carrying only the variant associated with increased VIP protein levels were linked to less intensive treatment requirements.

Since low levels of VIP in the blood are linked to worse disease courses and greater treatment requirements, these newly identified genetic variants “could be potential indicators of treatment requirements and, therefore, disease severity in patients with recent onset,” researchers wrote. The genotype associated with high VIP levels was also associated with less severe disease and thus with a reduced need for intensive treatment,” they added.

Overall, these results suggest that identifying variants in the VIP gene and how they associate with its protein levels in the blood could be a potential strategy to identify which patients may require more intense treatment.

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