Urine protein fragments may help assess kidney inflammation in AAV
Study: Potential biomarkers could provide therapeutic guidance
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ANCA-associated vasculitis (AAV) patients with antibodies targeting the myeloperoxidase (MPO) protein have higher levels of immune-activating pieces of the C3 protein in their urine, and these are closely associated with measures of disease severity, a small study showed.
“These fragments may serve as sensitive, [noninvasive] biomarkers for [kidney] immune activity and inflammation, providing novel tools for disease monitoring and potential therapeutic guidance in AAV,” researchers wrote.
The study, “Urinary complement C3 fragment levels and their clinical relevance in MPO-ANCA-associated vasculitis,” was published in Scientific Reports.
Average levels of all C3 fragment types were higher in AAV patients’ urine
AAV comprises a group of rare autoimmune disorders caused by self-reactive antibodies, called ANCAs, which ultimately lead to inflammation in small blood vessels, commonly those in the kidneys. ANCAs targeting the MPO protein are a common cause of AAV.
One of the main ways that ANCAs trigger inflammation is by activating a group of immune proteins called the complement cascade. Complement proteins are normally present in the blood in an inactive state. However, in response to an inflammatory stimulus, a chain reaction converts many of these proteins into active states.
As part of complement activation, a complement protein called C3 is cleaved into multiple fragments — C3a, C3b, iC3b, C3c, and C3d — that exert immune and inflammatory effects (except for C3c, which is inert).
Given that the kidneys are frequently affected in AAV, and that complement C3 fragments are eventually filtered out of the blood by the kidneys and excreted into the urine, detecting levels of these protein fragments in urine could plausibly be a useful strategy for monitoring AAV.
To test this idea, scientists in China analyzed the levels of C3a, C3b, iC3b, C3c, and C3d in urine samples from 22 people with MPO-associated AAV (81.8% women; mean age 71.9 years) and 20 age- and sex-matched healthy people.
Results showed that the average levels of all C3 fragment types were significantly higher in urine from AAV patients than in healthy controls.
BVAS score emerged as a consistent independent predictor of all fragments, reflecting their strong association with disease activity.
Statistical analyses in AAV patients showed that higher urine levels of C3 fragments were significantly associated with more severe body-wide disease, as measured by the validated Birmingham Vasculitis Activity Score (BVAS).
Higher urine C3 fragment levels were also significantly correlated with higher levels of protein and blood in urine, both of which are indicators of kidney damage. However, there was no significant association between urine levels of these fragments and blood creatinine levels, a marker of kidney health.
These data suggest that C3 fragments are a sign of inflammation and complement activation in the kidneys, but not necessarily reduced kidney function, the team noted.
“BVAS score emerged as a consistent independent predictor of all fragments, reflecting their strong association with disease activity,” the researchers wrote. “The particularly strong correlation between urinary C3 fragments and BVAS directly confirms that [body-wide] disease activity is closely coupled with intense, localized complement cleavage within the kidney.”
Collectively, the data suggest that measuring urinary C3 fragments may be a useful way to assess kidney inflammation in people with AAV noninvasively, the researchers concluded. They stressed, however, that this study was limited to a small number of patients, so further investigations are needed to validate and expand upon these findings.
