For Physicians
Understanding VEXAS Syndrome
Since patients with VEXAS syndrome share similar symptoms with some other inflammatory diseases, such as
It is recommended that these patients be tested for UBA1 mutations so that different treatment options can be applied to VEXAS patients to optimize their outcomes.
Differentiation from other Inflammatory Diseases
Testing Methods for UBA1 Somatic Mutations
in VEXAS Syndrome
Sanger Sequencing
Sanger sequencing can be used to detect UBA1 mutations in VEXAS syndrome, offering high accuracy and specificity for known mutations. However, it is limited by its lower throughput and inability to efficiently detect novel or low-frequency variants.
Next Generation Sequencing (NGS)
NGS is a powerful method for detecting UBA1 mutations in VEXAS syndrome, providing high sensitivity and the ability to detect a wide range of variants, though it can be costly and requires complex data analysis.
Droplet Digital PCR (ddPCR)
ddPCR is an advanced technique for identifying UBA1 mutations in VEXAS syndrome, known for its high precision and sensitivity in quantifying low-frequency mutations. The fluorescent colors limit its throughput, especially when more mutations of UBA1 are added to the list.
The DiaCarta Approach - XNA
DiaCarta’s high-throughput XNAxMAP combined technology allows ultra-sensitive, high-throughput, fast turnaround, and cost-effective testing of the UBA1 mutation. The ultra-sensitivity beats regular NGS tests and allows low-frequency UBA1 mutations as low as below 0.1%, helping early detection of VEXAS when the UBA1 mutation frequency is still low.
Benefits of the Early Detection
in VEXAS Syndrome
Early treatment with the right therapy
Without knowing the UBA1 mutation status, the VEXAS patients are usually treated for another disease such as MDS. However, VEXAS patients require different treatments. For instance, traditional immunosuppressive drugs are often not effective for VEXAS patients, and higher doses of corticosteroids, possible use of Jak2 inhibitors, and allogeneic hemopoietic stem cell transplant (AHSCT), the only agent with curative intent for VEXAS, may be used.
Early detection may slow down the disease progression. Since patients with VEXAS also have poorer survival rates than MDS patients, early detection may also extend the patient’s life.
Prognosis information
Even if the treatment may not prolong survival, the early test of the UBA1 mutation reveals the mutation information, which may affect the patient’s prognosis. For instance, patients with the codon 41 Valine mutation have poorer survival compared to the other two common codon 41 mutations, Leucine and Threonine.
Less damage for better treatment
Early detection of the UBA1 mutation allows the discovery of the VEXAs disease so the organs may not be severely damaged at diagnosis. This helps with AHSCT, which requires less organ damage.
