Aptamer-Based Test Identifies Biomarkers Linked to Neuropsychiatric Symptoms of Systemic Lupus Erythematosus

A novel aptamer-based diagnostic technique was used to identify proteins in cerebrospinal fluid (CSF) linked to neuropsychiatric symptoms of lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease triggered by genetic and environmental factors in which the immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, fatigue, and a red rash which is most commonly on the face. In addition, about half of those with SLE suffer neuropsychiatric symptoms including seizures, aseptic meningitis, acutely confused states, cerebrovascular disease psychosis, and mood disorders.

Since no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), investigators at the University of Houston (TX, USA) executed a broad screen of NPSLE cerebrospinal fluid (CSF) samples using an aptamer-based platform.

Aptamers are nucleic acid species that have been engineered through repeated rounds of in vitro selection to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues, and organisms. Aptamers are useful in biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of antibodies. In addition to their discriminate recognition, aptamers offer advantages over antibodies as they can be engineered completely in a test tube, are readily produced by chemical synthesis, possess desirable storage properties, and elicit little or no immunogenicity in therapeutic applications. Commercially available libraries of aptamers allow comprehensive screening of more than 1000 human protein targets, representing some of the largest screening platforms currently available in targeted proteomics.

For the current study, the investigators used an aptamer-based system to screen more than 1,100 proteins in the fluid surrounding the brains of neuropsychiatric lupus patients. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison with other neurological diseases.

Results revealed that 40 proteins out of 1129 screened were elevated in NPSLE CSF. By ELISA validation, CSF angiostatin, alpha2-macroglobulin, DAN (deadenylating nuclease), fibronectin, HCC-1 (chemokine (C-C motif) ligand 14), IgM, lipocalin 2, M-CSF (macrophage colony-stimulating factor), and SERPING1 (C1-inhibitor) were significantly elevated in a predominantly Caucasian NPSLE cohort, compared to patients with other neurological diseases. CSF IgM and M-CSF were the most discriminatory proteins. In a second, Hong Kong NPSLE cohort, CSF IgM and lipocalin-2 were the most discriminatory. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF C3 was associated with acute confusional state.

"These proteins emerged as promising cerebrospinal fluid biomarkers of NPSLE with diagnostic potential," said senior author Dr. Chandra Mohan, professor of biomedical engineering at the University of Houston. "Elevated CSF C3 was associated with acute confusional state. Eleven molecules elevated in the fluid exhibited concordant elevation in the choroid plexus, suggesting shared origins. We believe proteomic investigations of blood and cerebrospinal fluid will eventually lead to the fabrication of a serum or cerebrospinal fluid-based diagnostic panel that permits accurate diagnosis of NPSLE, with significantly higher specificity for this disease, compared to other neuroinflammatory diseases or infections."

The study was published in the January 31, 2022, online edition of the journal Arthritis & Rheumatology.

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