Initial screening for neuronal autoantibodies and their putative impact on survival in patients with small-cell lung cancer.

INTRODUCTION: Small-cell lung cancer (SCLC) may be associated with neuronal autoantibodies and paraneoplastic neurological syndromes. It has been suggested that neuronal autoantibodies, especially antineuronal nuclear antibody type 1 (Hu) autoantibodies, are associated with longer survival of patients with SCLC. The objective of this study was to determine the frequency and distribution of neuronal autoantibodies at the time of diagnosis of SCLC patients and assess survival rates in relation to autoimmunity. METHODS: In this retrospective study, serum from 40 patients with biopsy-proven SCLC at the time of diagnosis was studied prior to treatment. The sera originated from a cancer registry at the Oncology Department, Vejle Hospital from 2007 to 2010. The sera were analyzed blindly to clinical status for the presence of neuronal autoantibodies. Medical records were reviewed for neurological symptoms. RESULTS: Neuronal autoantibodies were detected in 22/40 (55%) of the SCLC patients. A broad range of neurological symptoms was recorded in 28/40 (70%) patients, of which 14/28 (50%) were positive for neuronal autoantibodies. The most frequently detected autoantibodies were Hu (7/40, 17.5%) followed by GAD65 (6/22, 15.0%). Striational and P/Q- or N-type voltage-gated calcium channel antibodies were less common, with each found in five patients (12.5%). Eight patients (20%) had coexisting autoantibodies. Autoantibody-positivity was not associated with survival. CONCLUSION: Neuronal autoantibodies were at time of diagnosis found in approximately half of the treatment-naïve SCLC patients. Neither autoantibody positivity at diagnosis nor neurological manifestations correlated with survival and their clinical importance requires further studies in larger, prospective cohorts.

Pathophysiological Effects of Autoantibodies in Autoimmune Encephalitides.

The heterogeneity of autoantibody targets in autoimmune encephalitides presents a challenge for understanding cellular and humoral pathophysiology, and the development of new treatment strategies. Thus, current treatment aims at autoantibody removal and immunosuppression, and is primarily based on data generated from other autoimmune neurological diseases and expert consensus. There are many subtypes of autoimmune encephalitides, which now entails both diseases with autoantibodies targeting extracellular antigens and classical paraneoplastic syndromes with autoantibodies targeting intracellular antigens. Here, we review the current knowledge of molecular and cellular effects of autoantibodies associated with autoimmune encephalitis, and evaluate the evidence behind the proposed pathophysiological mechanisms of autoantibodies in autoimmune encephalitis.