A peptide-based test may address some of the limitations of existing approaches to diagnosing and monitoring inflammatory diseases, according to a study published Wednesday in Nature Communications.
Physicians measure calprotectin, a protein found in white blood cells, when treating and monitoring patients with inflammatory diseases. Ulcerative colitis and Crohn’s disease, two forms of inflammatory bowel disease, are diagnosed and monitored by measuring the amount of the protein in stool samples. Similarly, tests of calprotectin levels in serum enable the monitoring of inflammation in patients with rheumatoid arthritis.
Diagnostic companies have developed lateral flow assays to enable the measurement of calprotectin concentrations. The assays feature antibodies that bind to calprotectin to detect the protein in a sample.
However, according to the authors of the Nature Communications paper, the antibody-based approach has limitations that can cause variability in the test results. The variability stems from the potential for antibodies to bind to different sites of the protein, as well as the risk that they will become inactivated over time as they unfold or bind to antigens.
Switching from antibodies to peptides may address the problems. Peptides, sequences of up to 50 amino acids, bind to proteins with high affinity and selectivity, making them suitable for use in lateral flow tests.
Peptides have multiple theoretical advantages over antibodies. They can be made chemically with high purity and homogeneity for less money than antibodies and with lower inter-batch variability, and are stable over time. In addition, peptides can attach to a specific location on the surface of a protein, potentially enabling the development of more accurate diagnostic tests.
Those factors led Christian Gerhold, chief technology officer at diagnostics company Bühlmann, to work with professor Christian Heinis’ team at Ecole Polytechnique Fédérale de Lausanne (EPFL) to develop human calprotectin ligands based on peptides. The collaboration resulted in the identification of a peptide that bound tightly enough to calprotectin to be a candidate for use in diagnostic tests.
Further work showed the peptide binds to a large surface region of calprotectin and to a specific form of the protein that is relevant to inflammatory diseases. Use of the peptide in lateral-flow cassettes determined that it was suited for detection and quantification of calprotectin, and a proof-of-concept study showed it can quantify the concentration of the protein in blood samples. Further work is underway.
“The EPFL and Bühlmann teams are currently performing more tests with the calprotectin-specific peptide to translate the assay into a product that can bring the diagnostic power of this increasingly important biomarker to a new level to help patients suffering from inflammatory diseases,” Heinis said in a statement.