The immunodeficiency disease: (CVID) severely compromises a person's ability to produce immunoglobulin (Ig) G antibodies (IgG), making them extremely vulnerable to infectious diseases. Early detection of CVID in this population can save lives.
Surface Plasmon Resonance (SPR) was able to detect differences in antibody characterization between CVID patients and a group of healthy control subjects. More conventional methods, such as micro-typing, did not. SPR's sensitivity, reproducibility and label-free technology gives clinicians a chance for early detection of diseases such as CVID; thus significantly improving clinical outcomes.
CVID is a heterogeneous illness summarized by deficiencies in antibody production. Patients with CVID have reduced serum levels of IgG, IgA and IgM and lack the ability to form new, high affinity antibodies to new antigens upon exposure to vaccination or infection. CVID patients also lack the ability of affinity maturation, meaning the antibodies they do produce also have low affinity compared to healthy antibody responses. Patients with untreated CVID can develop severe infections, autoimmune diseases and cancer. Therefore, early detection and initiation of a therapeutic plan is essential for long-term health. SPR's ability to quickly detect antibody levels as well as affinity binding of the antibodies makes it an ideal diagnostic tool.
Current diagnosis criteria include a history of repeated infections even after vaccination. Gene sequencing, radial immunodiffusion assay and T/B cell functional assays are among the tests administered. Due to the heterogeneity of the disease, with over 13 variations depending on particular gene mutations or immune phenotype presentation, current testing is laborious, costly and often requires weeks for test results to get back to patients.
Scientists using SPR technology are able to accurately and quickly analyze CVID patient serum antibodies for affinity abnormalities against immobilized synthetic blood group antigens A and B trisaccharides. This test can quickly determine whether the patient has abnormalities in their antibody production and can allow the immediate initiation of immunoglobulin replacement therapy before more severe disease sets in. Ideally, once the patient is stabilized, further testing can be done using gene sequencing to determine the exact nature of their particular CVID presentation; which can include - but is not limited to - a mutation in theTNFRSF13B orTACI genes, or IL-21 deficiency.
SPR technology gives clinicians and researchers several advantages over other testing methodologies. SPR testing can be conducted onsite, which expedites results to anxious patients. SPR is label-free, so this significantly reduces costs for additional reagents. It also reduces patient discomfort because a smaller sample size is required.
SPR can be included in the core pathology facility run by the hospital/clinic administration. Further economies can be realized by sharing equipment with different departments. Both patients and clinicians will appreciate the high sensitivity and reproducability of SPR technology.
The clinical application of SPR to detect defects in antibody formation is an important development in the quick and accurate diagnosis of CVID. SPR analysis can help diagnose specific antibody deficiencies in cases of CVID, which is a complex, heterogeneous immunodeficiency.
The developing immune system of young children makes them particularly susceptible to severe infection. As an immunosuppressive, a diagnosis of CVID contraindicates immunization. SPR’s ability to facilitate early diagnosis will help prevent future infections and, possibly, the development of autoimmune disease.