Neuronal Autoantibodies Tied to Cognitive Impairment in Lung Cancer

By Marilynn Larkin

July 09, 2021

NEW YORK (Reuters Health) - More than one-third of lung cancer patients had neuronal autoantibodies that were associated with cognitive impairment in a cross-sectional study in Germany.

The finding "suggests that these antibodies might represent an important factor in cancer-related cognitive impairment," Drs. Carsten Finke and Frederik Bartels of Charité - Universitätsmedizin Berlin told Reuters Health by email.

Rates of cognitive impairment and neuronal autoantibodies were "even higher than we had expected," they said. "Another surprise was that many patients had neuronal autoantibodies that were detected using immunohistochemistry, but had not yet been identified, and these antibodies were likewise associated with cognitive problems."

"Clinicians should be aware of cancer-related cognitive impairment, (which) is more common than previously thought and, importantly, can occur independent of any type of cancer therapy," they said.

As reported in JAMA Oncology, the single-center study included 167 patients (median age, 66; 63% men), 76% of whom had small-cell lung cancer (SCLC); the others had non-small-cell lung cancer (NSCLC). Detailed neuropsychological testing was performed in a selected subgroup of 97 patients that excluded those with potential confounding factors, such as brain metastases or a history of psychiatric disorders.

Brain-directed autoantibodies were detected in 61 patients (37%); 33 (19.8%) had known autoantibodies and, as Drs. Finke and Bartels indicated, 28 (17%) had autoantibodies against currently unknown antigens that were detected through immunohistochemical analysis.

Sixty-seven percent of patients had cognitive impairment. Among SCLC patients, the odds of cognitive impairment for those with any autoantibodies was 11-fold higher (odds ratio, 11.0) than for autoantibody-negative patients. The increased odds were independent of age, sex, and neurological deficit.

Among NSCLC patients, immunoglobin A autoantibodies targeting the N-methyl-D-aspartate receptor were associated with substantially higher odds of verbal memory deficits (OR, 182.8), especially with regard to delayed recall and recognition.

As indicated, autoantibodies against currently unknown antigens were also associated with increased odds of cognitive impairment (OR, 2.8).

The authors conclude, "These autoantibodies might represent a potentially treatable mechanism of immune-mediated cognitive impairment among patients with lung cancer."

Drs. Finke and Bartels said they have found a similar association of neuronal autoantibodies with cognitive deficits in other cancers, such as melanoma. "We are currently also looking into other cancer types, including breast cancer and prostate cancer, where we see the same association," they noted.

"However," they added, "the prevalence of neuronal autoantibodies and that of cognitive impairment appears to be highest in lung cancer patients."

Dr. Shawn Hervey-Jumper of the University of California, San Francisco, coauthor of a related editorial, commented in an email to Reuters Health, "It appears that the mechanistic drivers of cognitive impairments vary from one cancer type to another. However, there are likely general principles and common themes across patients with systemic cancer that we will see following further investigations."

"In this study, the authors uncovered the potential role of anti-neuronal antibodies," he said. "While these specific antibodies may not be relevant to many cancer types, there are other potential contributors to a proinflammatory and neurotoxic state within the central nervous system waiting to be uncovered."

"The approach used here...is a critical step towards defining the problem, understanding the mechanism, and applying new therapeutics," he concluded.

SOURCE: https://bit.ly/3hDRSmw and https://bit.ly/3dTNheS JAMA Oncology, online July 1, 2021.

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