Activated T cells in type I Charcot-Marie-Tooth disease: evidence for immunologic heterogeneity

Williams, Lowell L.; Shannon, Barry T.; O'Dougherty, Margaret; Wright, Francis S.

doi:10.1016/0165-5728(87)90108-1

Cited by 12 publications

(4 citation statements)

References 19 publications

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“…Of interest is the fact that multiple T-cell gamma receptor genes map to the same cytogenetic interval as CMT2D neuropathy. An autoimmune mechanism for CMT pathogenesis has been previously suggested by Williams et al based on significantly increased CD26 + T-cell activation found sequentially in CMT patients (17,18).…”

Section: Discussionmentioning

confidence: 87%

Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)

Ionâşescu

Searby

Sheffield

et al. 1996

Human Molecular Genetics

126

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Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe than of the feet with slow progressive course in 12 patients. Deep tendon reflexes were absent in the upper extremities and decreased in the lower extremities. There was distal hypesthesia for touch, proprioception and vibration sense for the hands more than for the feet. Motor nerve conduction velocities showed normal values (48-53 M/s) with normal latencies (2-3 msec) and electromyography revealed signs of denervation. Genetic linkage analysis used 167 short tandem repeat markers (STRPs) spaced throughout the 22 autosomes. Linkage to the short arm of chromosome 7 at 7p14 was found using the marker D7S435 (Z = 4.83 at theta = 0). Flanking markers were D7S1808 and D7S1806 and the genetic distance between them was 6.8 cM. The multipoint linkage analysis gave a peek multipoint lod score of 6.89 between the markers D7S1808 and D7S435. Linkage analysis showed significantly negative lod scores (with values less than -2) with markers of chromosomes 1 and 3 where CMT axonal forms have been previously mapped. PFGE analysis indicated the absence of the CMT1A duplication. Our findings are consistent with a new genetic type of axonal CMT neuropathy designated by us as CMT2D. Potential candidate genes are multiple T-cell gamma receptor genes which map to the same cytogenetic interval as CMT2D neuropathy.

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Section: Discussionmentioning

confidence: 87%

Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)

Ionâşescu

Searby

Sheffield

et al. 1996

Human Molecular Genetics

126

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“…Rather, it is plausible to assume that the involvement of the immune system as an aggravating component is not confined to hereditary neuropathies caused by P 0 -mutations, but might be widespread among the different types of hereditary neuropathies. Interestingly, in a variety of CMT patients of unknown genotype, elevated levels of activated T-lymphocytes have been detected in the peripheral blood (Williams et al, 1987(Williams et al, , 1992. Furthermore, some patients are reported to develop a sudden worsening of their clinical neuropathy and show inflammatory infiltrates in nerve biopsies (Malandrini et al, 1999) and clinically respond to corticosteroids (Dyck et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Immune Deficiency in Mouse Models for Inherited Peripheral Neuropathies Leads to Improved Myelin Maintenance

Schmid

Stienekemeier

Oehen³

et al. 2000

J. Neurosci.

113

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The adhesive cell surface molecule P 0 is the most abundant glycoprotein in peripheral nerve myelin and fulfills pivotal functions during myelin formation and maintenance. Mutations in the corresponding gene cause hereditary demyelinating neuropathies. In mice heterozygously deficient in P 0 (P 0 ϩ/Ϫ mice), an established animal model for a subtype of hereditary neuropathies, T-lymphocytes are present in the demyelinating nerves. To monitor the possible involvement of the immune system in myelin pathology, we cross-bred P 0 ϩ/Ϫ mice with null mutants for the recombination activating gene 1 (RAG-1) or with mice deficient in the T-cell receptor ␣-subunit. We found that in P 0 ϩ/Ϫ mice myelin degeneration and impairment of nerve conduction properties is less severe when the immune system is deficient. Moreover, isolated T-lymphocytes from P 0 ϩ/Ϫ mice show enhanced reactivity to myelin components of the peripheral nerve, such as P 0 , P 2 , and myelin basic protein. We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy.

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“…Clinical, [22][23][24] serological, 25 26 electrophysiological, 27 and histological [28][29][30][31][32] studies have suggested the existence of an inflammatory component in HMSN. Immune deficiency in a mouse model of a hereditary demyelinating neuropathy results in a less severe neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Immunological study of hereditary motor and sensory neuropathy type 1a (HMSN1a)

Gabriel

Gregson

Wood

et al. 2002

Journal of Neurology, Neurosurgery &Amp; Psychiatry

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Activated T cells in type I Charcot-Marie-Tooth disease: evidence for immunologic heterogeneity

Cited by 12 publications

References 19 publications

Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)

Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)

Immune Deficiency in Mouse Models for Inherited Peripheral Neuropathies Leads to Improved Myelin Maintenance

Immunological study of hereditary motor and sensory neuropathy type 1a (HMSN1a)

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