March 2026 Research Update

This month, registry data adds a clearer picture that recurrent fever in VEXAS often travels with a heavier overall illness, rather than being just an isolated symptom. In a registry of 87 people with VEXAS, fever was common and was linked to higher mortality and more frequent involvement of organs like the heart, lungs, and gastrointestinal system. The same analysis also reported that patterns of treatment response differed depending on whether fever was present and how high it ran, although these response patterns were not uniform across therapies. [1]

In this registry, 65 of 87 people had recurrent fever, and the presence of fever was tied to specific types of organ involvement, including cardiac, lung, and gastrointestinal problems. The study also reported links between fever and several inflammatory features such as lymph node swelling and pericardial effusion (fluid around the heart). These results help explain why some people with VEXAS experience a more complicated course when fevers keep coming back. [1]

The same study explored how fever related to treatment response categories across several drug groups used in routine care, and it reported differences by fever intensity in probability-based analyses. For example, very high fevers were reported alongside a high probability of failure with anti-IL-1 drugs, while some fever ranges were reported to have higher probabilities of partial (not complete) responses with drugs like tocilizumab and some JAK inhibitors. Because this was a retrospective registry analysis with small subgroups and wide uncertainty, these findings are better read as an early map of patterns rather than definitive comparisons between treatments. [1]

For patients and caregivers, this adds evidence that recurrent fevers in VEXAS may be a marker of a more severe or more organ-involving form of the condition, at least in the registry population studied. This does not prove that fever causes organ problems, but it does help clarify that fever can carry information about how the disease is behaving in the body. The treatment-response signals are exploratory and do not establish that one drug works better than another, but they highlight why people with similar diagnoses can experience different levels of benefit. What remains uncertain is how much these patterns depend on factors the registry could not fully control for, such as differences in disease duration, prior treatments, and how consistently symptoms were recorded. [1]

These studies add to the idea that VEXAS is linked to several types of UBA1 gene changes, and that different mutations can disrupt myeloid (bone-marrow-related) immune cells in different ways. A case series found UBA1 variants in 10 of 18 men with VEXAS-like illness and described 2 non-Met41 variants with lab evidence for distinct mechanisms. Separate laboratory work focusing on the UBA1 M41V change connected UBA1 loss of function to abnormal inflammatory behavior and abnormal cell death in monocytes/macrophages. Together, this month strengthens the picture that VEXAS is not one single mutation story, but a related set of problems centered on UBA1 and myeloid cells. [2] [3]

In the 18-person case series, most identified variants were at the Met41 position, but two people had different UBA1 changes that appeared harmful in functional tests. One variant (p.Ser56Phe) showed temperature-dependent reduction in UBA1 activity, and another (a splice-site variant) disrupted how UBA1 RNA was put together, reducing properly spliced transcript in lab testing. The study also reported that the mutation signal was stronger in myeloid cells than in lymphoid cells, matching the idea that VEXAS is driven mainly by abnormal myeloid blood cell lines. [2]

In laboratory and patient-cell experiments focused on UBA1 M41V, mutated monocytes showed TNF-alpha-triggered cell death through pathways involving RIPK1, and patient CD14+ cells showed abnormal apoptotic and necroptotic death. The same work reported weakened NF-kappaB signaling (a key inflammation-control pathway), reduced cFLIP(L), and blunted responses to certain immune triggers despite preserved receptor expression. Mutated macrophages also showed increased chemokine release and impaired clearance of dead cells (efferocytosis) linked to lysosomal dysfunction, offering a plausible chain from UBA1 dysfunction to ongoing inflammation. [3]

For patients and caregivers, these studies mainly add understanding of what sits underneath the diagnosis, rather than changing day-to-day care right now. The case series suggests that the genetic spectrum tied to VEXAS-like illness may be wider than the most commonly discussed Met41 changes, and it reinforces that testing may need to consider more than one possible harmful UBA1 variant. The laboratory study helps clarify why inflammation can be persistent and complex in VEXAS by showing multiple disrupted processes in myeloid cells, including how cells die and how they handle inflammatory signals. What remains uncertain is how directly these lab findings predict symptoms, organ involvement, or outcomes for an individual person, since laboratory models cannot capture the full clinical picture. [2] [3]

This month included a single case showing that lung findings in VEXAS can sometimes improve on their own over a short period, even when inflammation in the body continues. In an 86-year-old man with a UBA1 variant, chest imaging abnormalities improved and then stayed stable for 2 months without immunosuppressive treatment, while inflammatory symptoms and CRP remained elevated. This case adds a reminder that VEXAS can look different from person to person, including how lung involvement behaves over time. [4]

For patients and caregivers, this single-person report may be reassuring in one narrow way: it documents that some lung imaging changes in VEXAS can be self-limiting over weeks to months. At the same time, it does not show what usually happens, and it cannot predict whether another person would have a similar course. Its main value is adding detail to the range of possible experiences in VEXAS, which can be important when interpreting symptoms and imaging changes in the context of the whole illness. [4]