Increased systemic B- and T-lymphocyte responses in hereditary motor and sensory neuropathy (HMSN I).

Immune mechanisms of possible importance for the development and maintenance of peripheral nerve myelin breakdown in HMSN I were analysed by measuring B- and T-cell activation in blood, bone marrow and cerebrospinal fluid. Patients with polyneuropathies of other etiologies served as one control group and patients with tension headache as another. Flow cytometry of blood and bone marrow mononuclear cells revealed that an increased number of CD3+, CD4+ and CD4- CD8- T-cells expressed a late stage activation marker (Ta1). Analysis of T-cells primed for myelin antigens, by studies of IFN-gamma secretion in response to antigen in vitro, showed that both HMSN I and other polyneuropathy patients had low (but significant) numbers of T-cells recognizing whole PNS-myelin. Increased numbers of IgG- and IgM-producing cells were found in blood and bone marrow in the HMSN I patients. Patients with both HMSN I and the other polyneuropathies had few cells in peripheral blood and in bone marrow producing antibodies binding to P2, MAG and MBP in a solid phase immunospot assay. Many cells in the cerebrospinal fluid produced antibodies against MAG. Thus, there was a strong general activation of B- and T-cells in HMSN I while the immunity directed toward peripheral nerve was only slightly elevated. It is an open question if this immune activation is related to the primary gene defect or a secondary event to the nerve damage. The pathogenetic importance of the immune response in maintaining the nerve damage in HMSN I is unclear.