Autoantibodies associated with peripheral neuropathy

Quarles, Richard H.; Weiss, Michael D.

doi:10.1002/(sici)1097-4598(199907)22:7<800::aid-mus2>3.0.co;2-f

Cited by 126 publications

(33 citation statements)

References 192 publications

(241 reference statements)

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“…Even when this occurs it is often without clinical consequence, likely due in large part to the integrity of the blood-nerve barrier (243). Antibodies that attack peripheral nerves often arise by "molecular mimicry" ( Table 2).…”

Section: Antibody-mediated Nerve Damagementioning

confidence: 99%

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

Watkins

Maier

2002

Physiological Reviews

653

433

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Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibility that the reason for this failure lies in the fact that such drugs were designed to target neurons rather than immune or glial cells. It describes how immune cells are a natural and inextricable part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the etiology and symptomatology of diverse pathological pain states in both humans and laboratory animals. Of the variety of substances released by activated immune and glial cells, proinflammatory cytokines (tumor necrosis factor, interleukin-1, interleukin-6) appear to be of special importance in the creation of peripheral nerve and neuronal hyperexcitability. Although this review focuses on immune modulation of pain, the implications are pervasive. Indeed, all nerves and neurons regardless of modality or function are likely affected by immune and glial activation in the ways described for pain.

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Section: Antibody-mediated Nerve Damagementioning

confidence: 99%

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

Watkins

Maier

2002

Physiological Reviews

653

433

View full text Add to dashboard Cite

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“…The molecular targets of antibodies present in sera of patients with acquired peripheral nerve disease, such as IgM MGUS neuropathy, are often carbohydrate moieties expressed on cell surface glycoconjugates (Ho et al 1998;Quarles and Weiss 1999). In these cases, serum monoclonal antibodies that react with cell surface antigens may mediate nerve injury directly by complement-dependent attack on neural cells or by disruption of the normal function of the neural antigen.…”

Section: Discussionmentioning

confidence: 99%

“…Serum autoantibodies have been implicated as potential pathogenic agents in several autoimmune-mediated peripheral nerve disorders (Ho et al 1998;Quarles and Weiss 1999). In addition, a role of autoimmunity in peripheral nerve disorders associated with metabolic disturbances, such as diabetic neuropathy, has been entertained (Said et al 1994;Krendel et al 1995).…”

mentioning

confidence: 99%

Antibodies to L‐periaxin in sera of patients with peripheral neuropathy produce experimental sensory nerve conduction deficits

Lawlor¹,

Richards

Vries

et al. 2002

Journal of Neurochemistry

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L-Periaxin is a PDZ-domain protein localized to the plasma membrane of myelinating Schwann cells and plays a key role in the stabilization of mature myelin in peripheral nerves. Mutations in L-periaxin have recently been described in some patients with demyelinating peripheral neuropathy, suggesting that disruption of L-periaxin function may result in nerve injury. In this study, we report the presence of autoantibodies to L-periaxin in sera from two of 12 patients with diabetes mellitus (type 2)-associated neuropathy and three of 17 patients with IgG monoclonal gammopathy of undetermined significance (MGUS) neuropathy, an autoimmune peripheral nerve disorder. By comparison, anti-L-periaxin antibodies were not present in sera from nine patients with IgM MGUS neuropathy or in sera from 10 healthy control subjects. The effect of anti-L-periaxin serum antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-L-periaxin antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly (p < 0.005, n ¼ 3) attenuated sensory-evoked compound muscle action potential (CMAP) amplitudes in the absence of temporal dispersion. In contrast, motor-evoked CMAP amplitudes and latencies were not affected by intraneural injection of sera containing anti-L-periaxin antibody. Light and electron microscopy of anti-L-periaxin serum-injected nerves showed morphologic evidence of demyelination and axon enlargement. Depleting sera of anti-L-periaxin antibodies neutralized the serum-mediated effects on nerve function and nerve morphology. Together, these data support anti-L-periaxin antibody as the pathologic agent in these serum samples. We suggest that anti-L-periaxin antibodies, when present in sera of patients with IgG MGUS-or diabetesassociated peripheral neuropathy, may elicit sensory nerve conduction deficits. Keywords: antibody, diabetes, MGUS, neuropathy, periaxin. Peripheral neuropathies are a heterogeneous group of nerve disorders often characterized by a mixture of sensory and motor disturbances (Adams et al. 1997). Although the etiology of the peripheral neuropathy is often obscure, some patients exhibit strong familial histories consistent with an autosomal dominance, autosomal recessive, or X-linked pattern of inheritance. In other patients, the peripheral neuropathy is acquired such as in monoclonal gammopathy of undetermined significance (MGUS) neuropathy (Kyle 1992) or is secondary to a metabolic disturbance such as diabetes mellitus.Serum autoantibodies have been implicated as potential pathogenic agents in several autoimmune-mediated peripheral nerve disorders (Ho et al. 1998;Quarles and Weiss 1999). In addition, a role of autoimmunity in peripheral nerve disorders associated with metabolic disturbances, such as diabetic neuropathy, has been entertained (Said et al. 1994;Krendel et al. 1995). However, the antigenic specificities Abbreviations used: CMAP, compound muscle action potential; D/P, distal (ankle) to...

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“…On the contrary, the IgM antibodies generated against the myelin associated glycoprotein in anti-MAG neuropathies are identified as pathogenic with a successful transfer of the disease to the animals. The normal cellular interactions were also found to be disturbed by these anti-MAG antibodies by the complement activation towards the myelin lamellae (Latov, 1994;Dalakas & Quarles, 1996;Quarles & Weiss, 1999). The treatment options considered are mainly immunosuppressive in nature and administration of glucocorticosteroids, plasmapheresis and IVIg are in use (Shy, 2007).…”

Section: Polyneuropathies (Pn)mentioning

confidence: 99%