Research areas

Our focus areas are paraneoplastic neurological syndromes and paraneoplastic cerebellar degeneration.

Fig 1: Proposed mechanism for PNS: A tumour expresses onconeural antigens. Dendritic cells engulf apoptotic tumour cells and migrate to the lymph node where tumour antigens are presented to the immune system with subsequent activation of B- and T-cells. Activated B cells differentiate into antibody-secreting plasma cells that produce onconeural antibodies. Antibodies and cytotoxic T cells slow the growth of the tumour, but antibodies, plasma cells and cytotoxic T-cells can also cross the blood-brain barrier and target neurons that express these proteins.

Photo:

PNS group, UiB

Main content

Paraneoplastic neurological syndromes
Paraneoplastic neurological syndromes (PNS) are rare side effects of cancer that occur in less than 1 % of all cancer patients. It is most often associated with small-cell lung cancer, ovarian cancer and breast cancer. Detection of paraneoplastic antibodies is an important tool to diagnose PNS and the underlying cancer since the clinical manifestations often appear early in cancer development, while the tumour is still small. The type of antibody can give indications about the localization of the tumour. This means that the tumour can be identified at an earlier stage, specific cancer treatment can be started, and the chance for better recovery is increased.

The mechanism of PNS is largely unknown, but often the tumour expresses proteins that are normally only expressed in the nervous system. The immune system does not recognize these proteins from immune privileged sites as its own and produces antibodies and activates T-cells directed towards these proteins in an attempt to control tumour growth. Antibodies and T-cells cross the blood-brain barrier and react with proteins in the nervous system. This leads to loss of neurons and development of neurological syndromes.

Paraneoplastic cerebellar degeneration
Paraneoplastic cerebellar degeneration (PCD) is one of the best described forms of PNS. It mainly affects women with gynaecological or breast cancer. Anti-Yo is the antibody that is associated with PCD. PCD is caused by loss of Purkinje cells in the cerebellum, leading to severe cerebellar dysfunctions such as diplopia, dysarthria, tremor and ataxia and ultimately death. Some studies imply that Yo antibodies can cause Purkinje cell death, but the mechanism behind this process is yet unknown. Recent results from our laboratory suggest that Purkinje cell death is related to Yo antibodies by altering the Ca²⁺-balance in the cells, leading to “dark cell degeneration”. Yo antibodies have been found to recognize members of the so called cerebellar degeneration related (CDR) proteins. There are 3 known CDR proteins, namely CDR1, CDR2 and CDR2L. We have shown that Yo antibodies mainly recognize the CDR2 and CDR2L proteins, but sera from patients with PCD may also recognize CDR1.

06.06.2016