Study Identifies Association Between IL-35, Lupus Nephritis in SLE

In both blood and urine samples, patients with systemic lupus erythematosus and renal involvement were found to have higher levels of interleukin-35 compared with patients with systemic lupus erythematosus and no known renal involvement.

Patients with systemic lupus erythematosus (SLE) who have renal involvement have higher levels of interleukin (IL)-35 in blood and urine samples compared with patients without renal involvement, according to new research.

The study, published in the Central European Journal of Rheumatology, suggests IL-35 could be an important biomarker for identifying lupus nephritis (LN) in SLE, wrote author, Mary Atef Nassif, PhD, of Ain Shams University in Egypt.

SLE can affect multiple organs, but one of the most serious complications is LN. Atef Nassif said the current standard diagnostic method for LN is kidney biopsy, but she said the complicated mix of genetic, environmental, and immune factors at play in the pathogenesis of LN suggest there may be biomarkers that could give clinicians an early warning signal.

Atef Nassif said IL-35 is one potential biomarker, because it is already believed to play an immunosuppressive role in multiple autoimmune disorders, including SLE.

Citing promising research into correlations between IL-35 levels and inflammatory bowel disease and Sjögren syndrome, among others, Atef Nassif set out to better understand the immunosuppressive and anti-inflammatory roles of IL-35 in LN.

Atef Nassif recruited 42 adult patients with SLE. Twenty-two patients had evidence of LN and the remaining 20 patients did not. A control group of 20 age- and gender-match healthy participants was also included in the study.

Patients were excluded if they had other rheumatic or autoimmune diseases, renal diseases other than LN, and diabetes mellitus, among other criteria. Patients who had prior treatment with biologics, were undergoing hemodialysis, or had a history of renal transplantation were also excluded.

The study showed a significant relationship between IL-35 levels and kidney involvement.

“The present study showed that the levels of serum IL-35 were significantly higher in the LN group than in those without LN and controls,” Atef Nassif wrote.

Serum IL-35 levels ranged from 200-1500 pg/mL in patients with LN, versus 100-900 pg/mL in patients without LN. Urine IL-35 levels ranged from 0-9.195 pg/mg creatinine, versus 0-5.882 pg/mg creatinine.

The findings align with some—but not all—earlier research into IL-35 and LN, though Atef Nassif said she believes hers is the first study to use both urine and blood samples to assess IL-35.

“Our work indicated that the IL-35 biomarker possessed diagnostic value for LN as serum IL-35 had 90% sensitivity and 65% specificity while urine IL-35 had 86.4% sensitivity and 75% specificity to establish the diagnosis of LN in differentiation from SLE patients without nephritis,” Atef Nassif wrote. “In addition, to establish the diagnosis of LN in differentiation from healthy individuals, serum IL-35 had 90.9% sensitivity and 85% specificity while urine IL-35 had 95.5% sensitivity and 75% specificity.”

Atef Nassif said additional studies with larger sample sizes will be needed in order to confirm the findings and also identify links between IL-35 levels and different classes of LN. She said such studies should also investigate IL-35 expression in renal tissues.

“Also, further studies are needed to detect evidence about the specificity of IL-35 against other nephropathies or against kidney involvement in other inflammatory diseases such as vasculitis,” she concluded.


Nassif MA. Urine and serum interleukin 35 as potential biomarkers of lupus nephritis. Cent Eur J Immunol. Published online October 7, 2021. doi:10.5114/ceji.2021.109151