Dominant T-cell clones of unknown significance in patients with idiopathic sensory neuropathies

Objective: To determine whether idiopathic sensory neuropathies could be associated with circulating dominant T-cell clones, a T-cell equivalent to monoclonal gammopathy of unknown significance. Background: A number of predominantly sensory neuropathies remain of unknown etiology. Circulating dominant T-cell clones may be observed in the elderly, in autoimmune disorders, and in chronic viral infections. Methods: Twenty patients with chronic sensory or predominantly sensory neuropathies considered idiopathic after intensive investigation were evaluated for the presence of dominant T-cell clones in blood using PCR amplification of the variable region of the T-cell receptor gamma-chain gene. They were classified as chronic idiopathic axonal polyneuropathy (CIAP) or sensory neuronopathy, i.e., chronic idiopathic ataxic neuropathy (CIAN), according to clinical and electrophysiologic criteria. Results: Occurrence of clonal expansions of T cells was strikingly high in patients with idiopathic sensory neuropathies (16/20, 80%), with a similar proportion in CIAP (12/15, 80%) and CIAN (4/5, 80%), as compared with elderly normal controls (2/10, 20%), elderly controls with degenerative neurologic diseases (2/10, 20%), and elderly patients with idiopathic chronic inflammatory demyelinating polyneuropathy (2/10, 20%) (all p < 0.005). Conclusion: Both CIAN and CIAP are associated with dominant T-cell clones of unknown significance that cannot simply be attributed to the age of patients. Relevance of T-cell clones to the pathogenesis of idiopathic sensory neuropathies remains to be determined.