Table 3.

Representative antibodies against intracellular neuronal proteins and their associated clinical syndromes.

Antibody	Major central nervous system syndromes	Major associated neoplasms
Antibodies reacting with cytoplasmic and/or nuclear antigens
Anti-Yo (PCA1)	Subacute cerebellar degeneration [Recently renamed “Rapidly progressive cerebellar syndrome” (9)]	Carcinoma of the ovary, uterus, or fallopian tube; carcinoma of the breast
Anti-Hu (ANNA1)	Encephalomyelitis Subacute cerebellar degeneration Sensory neuronopathy Autonomic failure	Small cell lung carcinoma (Myxoid chondrosarcoma) (Merkel cell and other neuroendocrine tumors)
Anti-Ri (ANNA2)	Opsoclonus-ataxia syndrome Cerebella ataxia Encephalomyelitis	Breast carcinoma Small cell lung cancer
Anti-ANNA3	Limbic encephalitis Encephalomyelitis Progressive cerebellar syndrome	Small cell lung cancer
Anti-CRMP5	Encephalomyelitis Progressive cerebellar syndrome Chorea	Small cell lung cancer Non-small cell lung cancer Thymoma
Anti-Kelch-like protein 11	Brainstem and cerebellar syndromes Cerebellar ataxia	Ovarian, testicular, or other teratomas Seminomas
Anti-Ma 1 & 2	Limbic encephalitis, Brainstem encephalitis Progressive cerebellar syndrome	Ma1: Small cell lung carcinoma Ma2: testicular seminoma
Anti-SOX1	Progressive cerebellar syndrome	Small cell lung cancer (Non-small cell lung cancer)
Anti-Tra	Subacute cerebellar degeneration	Hodgkin's disease
Antibodies reactive with intracellular synaptic or other
membrane antigens
Anti-Amphiphysin	Stiff person syndrome Limbic encephalitis	Breast cancer Small cell lung cancer
Anti-GAD65	Stiff Person Spectrum Disorder Limbic Encephalitis Cerebellar ataxia	Tumor association rare (Multiple tumor types reported in individual patients: breast, lung, thymoma, other)

ANNA, antineuronal nuclear antibody; SCLC, small cell lung carcinoma; NSCLC, non- small-cell lung cancer; CRMP-5, collapsin response mediator protein 5; GAD, Glutamic acid decarboxylase; KLHL11, Kelch-like protein-11; PCA, Purkinje cell cytoplasmic antigen; DNER, delta/notch-like epidermal growth factor-related receptor.

^aAnti-Tr has been shown to react with glycosylated forms of the transmembrane delta/notch-like epidermal growth factor-related receptor (DNER). This protein is expressed intracellularly as well as at the neuronal cell membrane, and studies employing confocal and immune electron microscopy demonstrated anti-Tr immunolabelling of Purkinje cell cytosol, endoplasmic reticulum, dendrites as well as outer surface of the endoplasmic reticulum of neurons in the molecular layer (33, 34).