Blood Levels of Distinct Antibodies May Quickly Spot Lung Cancer in LEMS Patients, Study Says

Elevated levels of antibodies against certain proteins in the blood — SOX2, GABAb and N-type VGCC —  may help to more quickly identify small-cell lung cancer (SCLC) in people with Lambert-Eaton myasthenic syndrome (LEMS), a study suggests.

The study “Neuronal antibody detection and improved lung cancer prediction in Lambert-Eaton myasthenic syndrome” was published in the Journal of Neuroimmunology.

In LEMS, the immune system wrongly recognizes calcium channels as foreign, like the voltage-gated calcium channels (VGCC) of P/Q-type that are present at the contact point between nerve and muscle cells. This mistake triggers an immune reaction that results in loss of muscle contraction and muscle weakness.

SCLC is estimated to affect half of all LEMS patients, with one large study reporting it was detected within one year of a LEMS diagnosis in over 96% of patients it examined. The earlier lung cancer diagnosed and treated, the better a person’s likely outcomes.

A team of researchers in the U.K. investigated whether levels of certain antibodies circulating in blood could be used as biomarkers to detect lung cancer in LEMS patients. Previous studies suggest that the presence of antibodies against nerve cell proteins could help to identify cases of SCLC.

A total of 66 LEMS patients were recruited from October 2008 to September 2017. Each had a diagnosis confirmed by standard neurophysiological tests or by the presence of positive antibodies for the P/Q-type voltage gated calcium channel. Blood samples were collected from all at the time of LEMS diagnosis.

Of these people, 36 had associated SCLC (LEMS-SLCL). The majority, 34 out of 36 (94%), were diagnosed with LEMS before being diagnosed with SCLC; in most cases, the cancer was diagnosed within a median of six months after LEMS.

Compared to LEMS patients without SLCL, those with this cancer were significantly older at LEMS diagnosis (median age of 63; median of 58.5 in those without the cancer), had a weight loss of 5% or greater within three months of LEMS onset, and were tobacco smokers.

Nineteen, or about half, of LEMS-SLCL patients had a score below 70 in the Karnofsky Performance Scale (KPS), meaning they had significant functional impairments, compared to eight of the 30 without SLCL. The KPS scale ranges between zero to 100, with the highest score meaning no impairment.

LEMS-SLCL patients also had a higher scores (mean of 3.5) in the DELTA-P test, compared to those without SLCL (mean of 2.1). Delta-P score  (Dutch-English LEMS Tumour Association Prediction) is a clinical tool that predicts the risk of cancer in LEMS patients. The scale goes from zero to six, where a higher value is associated to a greater likelihood of SCLC.

Researchers next measured the levels of antibodies against neuronal proteins and SLCL cancer-linked antibodies, like those generated against the SOX2 protein, in the patients’ blood.

Levels of antibodies against calcium channels (P/Q-type and N-type), against neuronal proteins (called HuD and GABAb) and against the protein SOX2 were seen to be elevated in the LEMS-SLCL group compared to those with LEMS alone.

The presence of antibodies against SOX2, N-type VGCC, or GABAb identified cases of SCLC with high sensitivity (84%) and specificity (87%). A test’s sensitivity is its ability to correctly identify those with a given disease, while specificity refers to correctly identifying those without it.

Researchers also found higher levels of these antibodies in some patients (six of 21) with low DELTA- P scores when diagnosed with LEMS, meaning these scores did not always discriminate well between LEMS with and without this cancer.

“For patients with low DELTA- P scores [low to mid-range scores of 1 to 3] at LEMS diagnosis, checking for the presence of any one of these three antibodies will be useful in providing an additional, objective measure of the risk of SCLC,” the researchers wrote.

Overall, “we recommend screening patients for antibodies to GABAb, N-type VGCCs and SOX1/2 if either the initial DELTA-P score was 1 or 2, or a complete, accurate DELTA-P score could not be calculated,” they concluded.