Protein kinase Cgamma autoimmunity in paraneoplastic cerebellar degeneration and non-small-cell lung cancer

Background

The clinical and immunological profiles of patients with paraneoplastic cerebellar degeneration (PCD) and non‐small‐cell lung cancer (NSCLC) are not well known.

Objective

To review the clinical and immunological features of patients with PCD, NSCLC and without well‐characterised onconeural antibodies.

Methods

The clinical features of nine patients with the diagnosis of classical PCD and NSCLC, included in our archives, were retrospectively reviewed. The presence of antibodies to cerebellar components was determined by immunohistochemistry and immunoblot of rat cerebellum. A cDNA library of human cerebellum was screened with the positive sera to identify the antigen.

Results

Nine patients with PCD and NSCLC were identified. Six patients were men, and the median age at diagnosis of PCD was 63 (range 47–73) years. PCD was completely reversed in two patients, and partially in one, after treatment of the tumour. The serum of one of the patients with PCD showed a unique reactivity with Purkinje cells. The screening of a cerebellar‐expression library resulted in the isolation of protein kinase Cγ (PKCγ). PKCγ immunoreactivity was not observed in the serum of 170 patients with non‐paraneoplastic neurological syndromes, 27 patients with PCD, no onconeural antibodies and small‐cell lung cancer, and 52 patients with NSCLC without paraneoplastic neurological syndromes. The NSCLC from 11 patients without PCD did not express PKCγ at either the RNA or protein level. However, many cells of the NSCLC of the patient with PKCγ antibodies expressed PKCγ.

Conclusion

PCD occurs in patients with NSCLC without typical onconeural antibodies and is associated with immune reactions against key proteins of the Purkinje cells.Paraneoplastic cerebellar degeneration (PCD) is characterised by selective damage to the Purkinje cells of the cerebellum, which usually causes a severe pancerebellar syndrome.¹ In patients with lung cancer, PCD is almost always associated with small‐cell lung cancer (SCLC).² Patients with non‐small‐cell lung cancer (NSCLC) and PCD usually harbour onconeural antibodies typically associated with SCLC in the serum and cerebrospinal fluid, which probably indicate a common immune‐mediated mechanism of neuronal damage.^3,4 Although a few studies have indicated the occurrence of PCD in patients with NSCLC and no onconeural antibodies, these patients were usually included in larger series of patients with PCD with different tumours^2,5,6,7 or were reported as single observations.⁸In this study, we describe the clinical and immunological findings of a series of patients without previously characterised onconeural antibodies who presented with PCD associated with NSCLC.