Autoantibody Testing Detects SLE and Lupus Nephritis

Autoantibodies against Cytosine-phosphate-Guanine (CpG) DNA motifs are frequently found in patients with systemic lupus erythematosus (SLE), which may help rheumatologists diagnose SLE when a patient does not have antibodies against double-stranded DNA (anti-dsDNA), according to a study published in Lupus Science & Medicine.¹ Further, a correlation between antibodies against cytomegalovirus (anti-CMV) and lupus nephritis was reported.

“Although many different autoantibodies have been investigated in SLE, only a limited number of autoantibodies are being used in clinical practice,” investigators stated. “Due to these limitations, there has been great interest in the discovery of new autoantibodies that can be used in clinical practice.”

The study, which took place at the University Medical Center Utrecht (UMC Utrecht), in the Netherlands, utilized residual blood samples containing antibodies against double-stranded DNA (anti-dsDNA) collected between 2014 and 2017. Clinical data, which assessed symptoms and diagnosis, were obtained through electronic health records (EHR) via a text mining algorithm.

Patients with SLE were compared with 4 control groups: those with an immune-mediated inflammatory diseases (IMID) other than SLE (IMID control group), a non-IMID control group, those with medium levels of SLE suspicion but no clinical diagnosis (Rest), and healthy blood bank donors (BBD).

A chip-based, immunofluorescent microarray analyzed samples to determine the presence of 57 immunoglobulin G (IgG) autoantibodies. Some of the samples were selected for additional assessment.

In total, 1880 blood samples were collected for analysis. The autoantibody profiles of 483 patients diagnosed with SLE were compared with 690 patients in the non-IMID group, 361 healthy BBD, and 346 patients with another IMID. The average age of patients was 44.9 years and 63.4% were female. Approximately 30% (n = 248 of 836) had more than 1 diagnosis. Moreover, 40.5% of the patients diagnosed with SLE had overlap with at least 1 more diagnosis.

The most common symptom was fatigue (60.3%). Lupus nephritis, pericarditis, and pleuritis was present in 33.3%, 12.8%, and 14% of patients, respectively.

The most common antibodies seen in patients with SLE were anti-dsDNA (41.2%) and anti-CpG oligodinucleotides (CpG ODN 2216) (40.2%). Multiple autoantibodies were also seen more frequently in the SLE cohort when compared with non-IMID controls. Across all patients, 7.4% was positive for anti-CpG and negative for anti-dsDNA. For those with SLE, 8.9% was positive for anti-CpG antibodies and negative for anti-dsDNA antibodies.

Patients with SLE and nephritis had higher levels of Anti-CpG, anti-CMV (31.7% vs 17.8%), anti-Nucleosomes, anti-Histones, and anti-Saccharomyces cerevisiae antibody (anti-ASCA) (8.1% vs 1.6%) when compared with those without nephritis.

The large cohort, multiple control groups, and microarray system strengthened the study. Additionally, the autoantibodies studied have been previously reported in the serum of patients with SLE within other studies.

While the text mining algorithm is a reliable method, there is a possibility of misclassification of some patients. However, it has been proven to detect SLE in over 90% of patients. Another limitation is that immunosuppressive medication was not included in the analysis, which may have influenced the autoantibody levels and created a bias, thus showing a lower frequency of autoantibodies in that patient population.

“Our finding of a high prevalence of anti-CpG antibodies raises questions about their potential role in pathophysiology. Cross-reactivity of anti-CpG and anti-dsDNA antibodies, the preferred source of anti-CpG DNA, as well as the relation of anti-CpG antibodies with NETosis and CpG-rich mitochondrial DNA should be investigated,” investigators concluded. “Further research into anti-CpG autoantibodies can possibly provide new insights into the complex pathophysiology of this disease, leading to advances towards a reliable risk stratification and new treatment strategies.”

Reference:

Brunekreef T, Limper M, Melchers R, et al. Microarray testing in patients with systemic lupus erythematosus identifies a high prevalence of CpG DNA-binding antibodies. Lupus Sci Med. 2021;8(1):e000531. doi:10.1136/lupus-2021-000531