Rapid diagnosis of immuno-neurological disease with low-abundance inflammatory markers

Hello. My name is Professor Thomas Skripuletz. I'm working in the Department of Neurology at Hannover Medical School as a Senior Neurologist. My role here is to look after patients with different immunological diseases, such as multiple sclerosis or neuropathies.

It's not always easy to diagnose patients because we do not have enough markers to show that a patient has a disease at the onset. There is also a big challenge for the future to find new approaches, and new biomarkers in the blood or in the cerebrospinal fluid, to make a diagnosis faster, to be able to treat patients.

Oligoclonal bands are IgG antibodies and they show inflammation if they are found in cerebrospinal fluid. IgG antibodies consist of two heavy chains and two light chains. It is possible to analyze free light chains, such as kappa free light chains in the cerebrospinal fluid, to show inflammation as well.

Activated B cells do not produce solely intact, complete IgG antibodies, plasma cells produce kappa free and lambda free light chains as well. Kappa free light chains can be measured by different methods, but the problem is that in the cerebrospinal fluid, the amount is lower when compared to the blood, so you need a special assay. In Hannover, we use a latex-enhanced assay from Siemens, which allows the detection of low numbers of kappa free light chains, and for the analysis we use a Siemens nephelometer.

Using kappa free light chains, you measure the amount in the cerebrospinal fluid, and you measure the amount in the blood. Then you perform a ratio, as you need to show if the amount of kappa free light chains measured in cerebrospinal fluid is a product of inflammatory cells in the central nervous system.

In the last few years, different approaches have been used to show if the amount of measured kappa free light chains are a product of inflammation. Since last year, we have a new diagram published by Dr. Reiber, who also introduced the Reiber diagrams for the antibodies IgG, IgA, and IgM. We compared the new diagram with oligoclonal bands, and we could show that the kappa free light chains are a very promising biomarker for the future and every lab in the world can use it very easily.

For example, we had 99 patients with positive oligoclonal bands, and by measuring kappa free light chains and using the Reiber diagram to show if the kappa free light chains are elevated in the cerebrospinal fluid, only one patient less would have been detected as an inflammatory patient. This is really great.

The detection of oligoclonal bands is a sensitive, traditional method to show inflammation, but you need an expert in the lab. So, by using the measurement of kappa free light chains, with an automated program, you get the results very quickly and on the same day. It's easy to perform, so that's why I think it's a beneficial biomarker for the future. It can be used in each lab, because it's difficult to have experts for the detection of oligoclonal bands, as we have in Hannover for example.

Future projects aim to extend my cerebrospinal fluid research, including measuring kappa free light chains in other neurological diseases like immune-mediated neuropathies and Sjögren's syndrome for example.