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Although saliva production is reduced in individuals with Sjögren syndrome, saliva may still serve as a valuable, noninvasive source of novel biomarkers. 

The same may be true for rheumatoid arthritis (RA), according to Ulf Müller-Ladner, MD, professor and director of the Department of Rheumatology and Clinical Immunology at Kerckhoff Klinik in Bad Nauheim, Germany, who spoke at Rheumatology Update 2026. In systemic lupus erythematosus (SLE), urine may provide substantially more information about lupus nephritis than previously recognized, extending beyond proteinuria and abnormalities detected in urine sediment analysis.

“We want biomarkers that either enable diagnosis or provide prognostic information,” Müller-Ladner said. “Serum and biopsies do not always have to be the only sources of valid biologic samples for immune-mediated diseases.”

Biopsies are highly invasive, and blood-based measurements do not always accurately reflect disease activity within the affected organs. Saliva, in particular, has likely been underestimated as a source of biomarkers, Müller-Ladner noted while presenting new data supporting its potential clinical value.

New Phenotype

Examining saliva in patients with Sjögren syndrome is a logical approach because it originates from one of the organs most directly affected by the disease.

In a cross-sectional study, US researchers collected unstimulated saliva samples from 446 individuals with confirmed Sjögren syndrome and seronegative non-Sjögren sicca. Using enzyme-linked immunosorbent assay and Western blot analyses, the researchers assessed the samples for anti-Ro60 and anti-La antibodies, as well as immunoglobulin G and immunoglobulin A rheumatoid factors. They then compared the findings with other clinical measures, including the Schirmer test results.

Researchers have identified what may represent a previously unrecognized Sjögren syndrome phenotype. Among 88 individuals with seronegative non-Sjögren sicca, 75 had clinically verifiable dry mucous membranes and tested negative for disease-specific autoantibodies in serum but positive for salivary anti-Ro60 antibodies.

“If someone reports dry eyes and possible immune-related symptoms, analyzing saliva for antibodies could help establish the diagnosis earlier,” Müller-Ladner said, summarizing the researchers’ conclusions.

He described the findings as “really exciting.”

“Let’s see whether this eventually becomes part of the classification criteria,” he added.

Müller-Ladner also highlighted a similar study involving individuals with RA and healthy volunteers. Researchers examined secretions collected throughout the digestive tract, including saliva, for RA-associated autoantibodies, specifically antibodies against citrullinated proteins (ACPA), carbamylated proteins, and acetylated proteins.

All three autoantibody types were detected in saliva samples from ACPA-positive individuals with RA, with a prevalence ranging from 9% to 40%. None were detected in the intestinal samples.

Whether the findings from either study will improve early diagnosis remains uncertain.

“Validation studies are, of course, necessary,” Müller-Ladner emphasized.

Urine Clues

In SLE, another bodily fluid, urine, may provide particularly valuable information.

Because kidney involvement is associated with substantial morbidity and mortality, routine screening includes serum kidney function testing, urine protein-to-creatinine ratio assessment, and urine sediment analysis. When lupus nephritis is suspected, renal biopsy is necessary. However, urinary biomarkers may provide more specific information about the underlying renal pathology.

Using proteomic analyses, Japanese researchers examined urine samples from individuals with biopsy-confirmed lupus nephritis. Through cluster analyses and correlations with urinary protein profiles, they identified five histopathologic subgroups.

“Validation using an enzyme-linked immunosorbent assay revealed that urinary concentrations of calgranulin B (S100A9), monocyte chemoattractant protein 1 (MCP-1), and insulin-like growth factor-binding protein 5 (IGFBP-5) specifically predict the presence and severity of active glomerular lesions, interstitial inflammation, and interstitial fibrosis,” Müller-Ladner explained.

This story was translated from Medscape’s German edition.