Osteopontin Levels Linked to Poor Kidney Function, Higher Disease Activity in SLE Patients, Study Reports

In patients with recent-onset systemic lupus erythematosus (SLE), higher levels of a protein called osteopontin seem to be associated with lupus nephritis and more disease activity, but not with the development of organ damage over five years, according to a study.

The study, “Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort,” appeared in The Journal of Rheumatology.

Osteopontin is a protein found in the extracellular matrix, which provides structural and biochemical support to cells. Local production and increased levels of this protein in the blood have been reported in several autoimmune disorders, including SLE.

In mice, elevated osteopontin levels induce activation of immune B-cells and subsequent generation of anti-dsDNA antibodies, an SLE hallmark. In cells, this protein is required for the production of interferon-gamma, a key molecule in SLE.

Patients with SLE have shown elevated levels of osteopontin. In addition, higher levels of this protein have been associated with SLE disease activity and organ damage, as well as with lupus nephritis, a type of kidney inflammation that occurs frequently in SLE.

Using a group of recent-onset SLE patients — from 33 centers in 11 countries in North America, Europe, and Asia — researchers prospectively assessed if increased serum levels of osteopontin predicted organ damage, reflected disease activity, and correlated with specific disease manifestations.

A total of 344 patients (315 women, with a mean age of 34 years) were included from the Systemic Lupus International Collaborating Clinics Inception Cohort. All participants were enrolled within 15 months of their SLE diagnosis and had five years of follow-up data available. No patient had organ damage at the beginning of the study. A group of 344 population-based controls (315 women, with a mean age of 34.4 years) was also included.

On an annual basis, disease activity was assessed using SLE Disease Activity Index 2000 (SLEDAI-2K) and damage using the SLICC/ACR Damage Index. Serological activity was also analyzed.

Patients with SLE had much higher levels of circulating osteopontin than the control group, which decreased with advancing age. In the SLE group, men showed higher levels than women, but no gender differences were found in initial disease activity.

Caucasian patients had lower levels of osteopontin and lower disease activity than non-whites.

The data showed that osteopontin levels failed to predict organ damage of any severity, although age and disease activity at the study’s start were significant predictors of damage at five years.

Osteopontin levels correlated with disease activity and blood markers at enrollment. Osteopontin was elevated in patients positive for anti-dsDNA, which was also true for patients with low levels of complement system proteins C3 and/or C4 — markers of inflammation — and people with a SLEDAI-2K score of five or greater, indicating high disease activity.

Evidence of lupus nephritis and low kidney function was also associated with higher levels of osteopontin.

The team then found that patients with persistent disease activity — defined as SLEDAI-2K scores of at least five on three or more separate occasions — also had higher levels of osteopontin.

“In early SLE, [osteopontin] is elevated and appears to be associated with renal involvement and higher disease activity,” the scientists wrote. “We suggest that raised [osteopontin] at SLE onset identify cases with risk of high and persistent disease activity but may not necessarily lead to accrual of damage within 5 years of followup,” they said.

Among the study’s limitations, the team mentioned only measuring protein levels at the study’s start, the different proportions of whites in the two groups, and the possibility that enrolled patients had already started treatment with immunosuppressants or antimalarials.