Background/Purpose: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease in which a variety of autoantibodies contribute to the diversified disease phenotypes. In our previous studies, we generated more than 300 recombinant antibodies from B cells of SLE patients using the single-cell RT-PCR approach. We found that over 20% of SLE-derived antibodies bind to and activate neutrophils. One of the antibodies recognizes a novel pattern recognition receptor Nucleotide-binding Oligomerization Domain 27 (NOD27), which is recently shown to be involved in anti-viral interferon responses. Administration of this antibody in lupus-prone mice accelerated lupus progression, suggesting a role of anti-NOD27 in lupus pathogenesis. The purpose of this study is to determine if anti-NOD27 autoantibodies are detectable in sera from SLE patients and if the serum levels of anti-NOD27 are elevated in SLE patients with active disease.

Methods: 59 SLE patients who met at least four of the 1982 ACR criteria and 92 healthy volunteers with no known rheumatic diseases were enrolled into the prospective study. The SLEDAI disease activity index was obtained in all patients. Patients with a SLEDAI score of 6 or higher were considered to have active disease. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum levels of anti-NOD27 antibodies. Serum titers of complements C3 and C4 and anti-dsDNA antibodies were obtained in each patient. The control group, SLE group and the SLE inactive and active groups were compared with each other for the serum titers of anti-NOD27 using the Mann Whitney test (two-tailed). A pvalue of <0.05 was considered significant. The respective correlation of anti-NOD27 titers with anti-dsDNA, C3, C4, or SLEDAI in SLE patients was calculated using Pearson’s correlation test.

Results: The mean anti-NOD27 level in the SLE group was 0.518 (in optical density units; SD 0.26, 95% CI 0.45-0.587), which is significantly higher than that in the control group (mean: 0.398; SD 0.15, 95% CI 0.36-0.45; p=0.0019). The mean anti-NOD27 level of the active SLE cohort was found to be higher than that of the inactive SLE cohort (mean: 0.617 versus 0.496) although the difference was not statistically significant, likely related to the limited number of active patients in our cohort (11 of 59). The anti-NOD27 titers were significantly correlated with anti-dsDNA titers (p=0.0014, Pearson r =0.38) and demonstrated a marginal inverse correlation with the C3 levels (p=0.047, Pearson r = -0.22). No significant correlation of anti-NOD27 with C4 levels (p=0.118, Pearson r =-0.16) nor SLEDAI scores (p=0.074, Pearson r =0.19) was seen.

Conclusion: The novel biomarker anti-NOD27 was found to be significantly elevated in patients with SLE compared to controls in this study and concentrations of anti-NOD27 were significantly correlated with anti-dsDNA titers in our cohort of SLE patients suggesting that anti-NOD27 may be an informative biomarker in SLE. Further studies with larger sample sizes and different cohorts of patients including those with active disease and end organ damage will be needed to evaluate the predictive capacity of NOD27 antibody responses in the future.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-biomarker-nucleotide-binding-oligomerization-domain-27-in-systemic-lupus-erythematosus/