Feasibility of Saliva-Based Autoantibody Detection in Systemic Lupus Erythematosus

Objectives Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can be detected using serum-based immunoglobulin G (IgG) autoantibody testing. However, this approach requires venipuncture, trained personnel, and laboratory infrastructure—limiting accessibility in remote/low-resource settings. Saliva contains immunoglobulins A and G (IgG). This pilot study aimed to evaluate the feasibility of detecting IgG autoantibodies in saliva samples from SLE patients and assess concordance with serum-based testing. Methods Paired serum and saliva samples were collected from SLE patients and healthy controls. Serum was collected by venipuncture and stored at −80°C. Saliva was collected by 1) swab brushing of the gingival crevicular fluid on the gum line, enhancing IgG capture, or 2) passive drooling. Saliva was stored at −20°C. Antinuclear antibodies (ANA) were detected by conventional indirect immunofluorescence on HEp-2 cells (NOVA Lite, Werfen; cut-off >= 1:80), and for a subset of participants, SLE-related antibodies were quantified by QUANTA Lite ELISA for dsDNA (n=6 SLE, n=3 healthy controls), and FIDIS Connective Luminex 100 (Biosynx, Theradiag) for the remaining antibodies, anti-U1-RNP, histone, Jo-1, Pm-Scl, PCNA, Ro62/TROVE2, Ro52/TRIM21, SSB/La, Sm, Sm/RNP, Scl-70, ribosomal P, and centromere B (n=18 SLE, n=6 healthy controls). Results We included 19 SLE patients and 6 healthy controls. Among these participants, 16 SLE patients (84.2%) and one (16.7%) healthy control were serum-positive for ANA. With gum line brushing, ANA positivity was observed in 10/16 (62.5%) of serum-positive SLE cases (Figure), and in one (100%) serum-positive healthy control. End-point ANA titers were reduced in saliva-positive cases relative to serum, with an average change of 2 dilution factors. When expert-level ICAP ANA patterns were included, 4/10 (40%) were congruent. There was a trend toward moderate correlation in anti-dsDNA titers between serum and saliva (r=0.65, p=0.06). For the remaining autoantibodies, where the presence or absence of any antibody in the ENA panel was considered a positive or negative ENA, 8/14 (57.1%) of the serum/saliva samples were in agreement. None of the passive drooling samples were ANA, anti-dsDNA, or ENA positive. Figure. Comparison of antinuclear antibody (ANA) detection by indirect immunofluorescence on HEp-2 cells across paired serum and saliva samples from two systemic lupus erythematosus (SLE) patients. Representative HEp-2 cell images show ANA pattern of AC-5 (nuclear large/coarse speckled) in paired ( A ) serum (1:1280) and ( B ) saliva stored at −20°C (1:320) for one SLE patient. ANA pattern of AC-4 (nuclear fine speckled) depicted in paired ( C ) serum (1:1280) and ( D ) saliva stored at −20°C (1:160) for a different SLE patient. Conclusion Saliva collected by brushing the gum line represents a promising matrix for autoantibody detection in SLE, particularly for ANA screening and anti-dsDNA titers. This minimally invasive approach can be self-administered and easily transported to laboratories equipped for diagnostic testing. Ongoing studies aim to optimize autoantibody detection and further validate the method in larger cohorts.