Sequential antibodies to potassium channels and glutamic acid decarboxylase in neuromyotonia
ABSTRACT A patient with thymoma-associated neuromyotonia and voltage-gated potassium channel (Kv1.2 and Kv1.6) antibodies by immunoprecipitation and rat brain immunolabeling was treated successfully with immunoadsorption and cyclophosphamide. Curiously, glutamic acid decarboxylase antibodies, absent at onset, appeared later. Stiff-person syndrome was absent, but fast blink reflex recovery suggested enhanced brainstem excitability. The range of antibodies produced in thymoma-associated neuromyotonia is richer, and the timing of antibody appearance more complex, than previously suspected.
- SourceAvailable from: Cinthia Farina
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- "IgG were obtained by PAI treatment from the patient with MS, or from control patients affected by Lambert–Eaton myasthenic syndrome (LEMS), an autoimmune disorder of the neuromuscular junction, or type 1 diabetes mellitus (T1DM), an autoimmune disorder of the pancreatic islets, who underwent the same PAI protocol (Antozzi et al., 2005). MS patient's IgG used in all of the experiments were from the first PAI session performed during the first clinical relapse. "
ABSTRACT: The pathogenic role of antibodies in multiple sclerosis (MS) is still controversial. We transferred to mice with experimental autoimmune encephalomyelitis (EAE), animal model of MS, IgG antibodies purified from a MS patient presenting a dramatic clinical improvement during relapse after selective IgG removal with immunoadsorption. Passive transfer of patient's IgG exacerbated motor paralysis and increased mouse central nervous system (CNS) inflammation and demyelination. Binding of patient's IgG was demonstrated in mouse CNS, with a diffuse staining of white matter oligodendrocytes. These data support a growing body of evidence that antibodies can play an important role in the pathobiology of MS.Journal of neuroimmunology 06/2013; 262(1-2). DOI:10.1016/j.jneuroim.2013.05.010 · 2.79 Impact Factor
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- "Eleven patients were diagnosed by their neurologists as having neuromyotonia only, but four of these had pain, autonomic dysfunction or insomnia, features that could be ascribed to Morvan's syndrome, suggesting considerable overlap between the two syndromes. Previous immunohistological data on a small number of high titre VGKC-antibody positive limbic encephalitis and Morvan's syndrome sera suggested co-localization with Kv1.1 or 1.2, or occasionally Kv1.6 (Buckley et al., 2001; Liguori et al., 2001; Ances et al., 2005; Antozzi et al., 2005; Kleopa et al., 2006). Having identified the true targets for the antibodies in these patients , it appears that these results were confounded by the very similar localization of Lgi1 and Kv1.1, particularly in the hippocampus , and of Caspr2 and Kv1.2 (Kv1.2 not shown here but can be seen in Kleopa et al., 2006), both in the hippocampus and cerebellum . "
ABSTRACT: Antibodies that immunoprecipitate (125)I-alpha-dendrotoxin-labelled voltage-gated potassium channels extracted from mammalian brain tissue have been identified in patients with neuromyotonia, Morvan's syndrome, limbic encephalitis and a few cases of adult-onset epilepsy. These conditions often improve following immunomodulatory therapies. However, the proportions of the different syndromes, the numbers with associated tumours and the relationships with potassium channel subunit antibody specificities have been unclear. We documented the clinical phenotype and tumour associations in 96 potassium channel antibody positive patients (titres >400 pM). Five had thymomas and one had an endometrial adenocarcinoma. To define the antibody specificities, we looked for binding of serum antibodies and their effects on potassium channel currents using human embryonic kidney cells expressing the potassium channel subunits. Surprisingly, only three of the patients had antibodies directed against the potassium channel subunits. By contrast, we found antibodies to three proteins that are complexed with (125)I-alpha-dendrotoxin-labelled potassium channels in brain extracts: (i) contactin-associated protein-2 that is localized at the juxtaparanodes in myelinated axons; (ii) leucine-rich, glioma inactivated 1 protein that is most strongly expressed in the hippocampus; and (iii) Tag-1/contactin-2 that associates with contactin-associated protein-2. Antibodies to Kv1 subunits were found in three sera, to contactin-associated protein-2 in 19 sera, to leucine-rich, glioma inactivated 1 protein in 55 sera and to contactin-2 in five sera, four of which were also positive for the other antibodies. The remaining 18 sera were negative for potassium channel subunits and associated proteins by the methods employed. Of the 19 patients with contactin-associated protein-antibody-2, 10 had neuromyotonia or Morvan's syndrome, compared with only 3 of the 55 leucine-rich, glioma inactivated 1 protein-antibody positive patients (P < 0.0001), who predominantly had limbic encephalitis. The responses to immunomodulatory therapies, defined by changes in modified Rankin scores, were good except in the patients with tumours, who all had contactin-associated-2 protein antibodies. This study confirms that the majority of patients with high potassium channel antibodies have limbic encephalitis without tumours. The identification of leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 as the major targets of potassium channel antibodies, and their associations with different clinical features, begins to explain the diversity of these syndromes; furthermore, detection of contactin-associated protein-2 antibodies should help identify the risk of an underlying tumour and a poor prognosis in future patients.Brain 09/2010; 133(9):2734-48. DOI:10.1093/brain/awq213 · 10.23 Impact Factor
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ABSTRACT: This study examined the influence of social support (perception and utilization) on diabetic control. Subjects were 178 patients with diabetes mellitus [insulin dependent diabetes mellitus (IDDM) = 26, non-insulin dependent diabetes mellitus (NIDDM)= 152]. HbA1c values was used as an indicator of diabetic control. Assessment of social support was performed using the Stress and Coping Inventory. HbA1c values were significantly related to the presence or absence of participation in a diabetic education program as well as scores on perception and utilization of social supports. The participation in the diabetic education program was not significantly associated with the two social supports, however, the two social support factors interacted significantly with one another. As for type of DM, these findings were stronger in IDDM patients. These results suggest that, in particular patients with NIDDM, although diabetes education is effective for decreasing HbA1c, a combination of the two social supports also decrease the HbA1c value, independent of diabetic education.Diabetes Research and Clinical Practice 10/1998; 41(3):207-11. DOI:10.1016/S0168-8227(98)00083-7 · 2.54 Impact Factor