Transglutaminase 6 antibodies in gluten neuropathy.

BACKGROUND: TG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored. We investigated the presence of TG6 antibodies in gluten neuropathy (GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies). METHODS: This was a cross-sectional study conducted at the Sheffield Institute of Gluten Related Diseases, Royal Hallamshire Hospital, Sheffield, UK. Blood samples were collected whilst the patients were on a gluten containing diet. Duodenal biopsies were performed to establish the presence of enteropathy. RESULTS: Twenty-eight patients were recruited (mean age 62.5±13.7 years). Fifteen (53.6%) had sensory ganglionopathy, 12 (42.9%) had symmetrical axonal neuropathy and 1 had mononeuritis multiplex. The prevalence of TG6 antibodies was 14 of 28 (50%) compared to 4% in the healthy population. TG6 antibodies were found in 5/15 (33.3%) patients with sensory ganglionopathy and in 8/12 (66.7%) with symmetrical axonal neuropathy. Twenty-four patients underwent duodenal biopsy 11 (45.8%) of which had enteropathy. The prevalence of TG6 was not significantly different when comparing those with or without enteropathy. CONCLUSIONS: We found a high prevalence of antibodies against TG6 in patients with GN. This suggests that TG6 involvement is not confined to the central nervous system. The role of transglutaminase 6 in peripheral nerve function remains to be determined but TG6 antibodies may be helpful in the diagnosis of GN.

Treatment for cutaneous arteritis patients with mononeuritis multiplex and elevated C-reactive protein.

Cutaneous arteritis (cutaneous polyarteritis nodosa, CA) is a necrotizing vasculitis of arteries within the skin. CA is a new classification under single-organ vasculitis, as adopted by the 2012 Chapel Hill consensus conference (CHCC 2012). Some patients originally diagnosed as having CA could develop additional disease manifestations that warrant reclassifying as systemic polyarteritis nodosa (PAN) according to the CHCC 2012. We retrospectively investigated 101 patients with CA seen at our department between 2003 and 2012. There was a significantly higher frequency of inflammatory plaques and leg edema in CA patients with elevated C-reactive protein (CRP) compared to CA patients with normal CRP. Similarly, there were significant differences in the incidence of arthralgia and mononeuritis multiplex between the two patient groups. We found significantly positive correlations between CRP and creatinine titers in serum in all 101 CA patients. Prednisolone was administrated in a significantly greater percentage of patients with elevated CRP compared to patients with normal CRP. Repeated i.v. cyclophosphamide pulse therapy (IV-CY) with prednisolone therapy at an early stage resulted in complete resolution without adverse effects or severe complications. We regard inflammatory plaques and leg edema with elevated serum CRP as an indication of a more severe condition, and treated them effectively with prednisolone. Assuming mononeuritis multiplex and/or arthritis exist with elevated CRP, we propose that earlier treatment by IV-CY with prednisolone should be indicated for CA patients who demonstrate these more severe manifestations to prevent progression to PAN.

[Patient with hypertransaminasemia and mononeuritis multiplex]. / Paciente con hiperaminotransferasemia y mononeuritis múltiple.

We present the case of a 57-year-old man with mononeuritis multiplex and high transaminase levels. After investigations, the patient was diagnosed with acute hepatitis B infection and polyarteritis nodosa (PAN). The symptoms of PAN are nonspecific. Nervous system involvement in the form of mononeuritis multiplex can be one of the forms of presentation. PAN is one of the extrahepatic manifestations of hepatitis B, but since the introduction of the hepatitis B vaccine, its incidence has markedly declined. After 1 year of follow-up, the patient is asymptomatic following treatment with antiviral drugs and steroids.

Multiple mononeuropathy due to vasculitis associated with anticardiolipin antibodies: a case report.

This report illustrates a case of peripheral nerve vasculitis associated with elevated anticardiolipin antibodies. A 49-year-old female with a history of seven spontaneous abortions initially complained of pain and numbness in her right calf that later spread to the left foot and ankle. Over the next few months, she developed a Raynaud phenomenon and livedo reticularis. Clinical examination revealed signs of multiple mononeuropathy. Right sural nerve biopsy performed two months after the beginning of the disease revealed active necrotizing arteritis of the epineural arteries with transmural inflammatory infiltrate and thrombosis. Vasculitis is a rare finding in sural nerve biopsies, usually in patients with systemic vasculitis or autoimmune connective tissue diseases. However, vasculitis restricted to the peripheral nerves has also been described. Our patient had no clinical or laboratory features of any autoimmune disorder and also no signs of systemic vasculitis. We discuss the potential role of anticardiolipin antibodies in the pathogenesis of vasculitis.

Population pharmacokinetic-pharmacodynamic modelling of the anti-hyperalgesic effect of 5'deoxy-N6-cylopentyladenosine in the mononeuropathic rat.

The objective of this investigation was to characterise the pharmacokinetic-pharmacodynamic correlation of 5'-deoxy-N6-cyclopentyl-adenosine (5'dCPA) in the chronic constriction injury model of neuropathic pain. Following intravenous administration of 5'dCPA (0.30 or 0.75 mg kg(-1)), the time course of the drug concentration in plasma was determined in conjunction with the effect on (1) the mechanical paw pressure and (2) the Von Frey Hair monofilament withdrawal threshold. Population pharmacokinetic-pharmacodynamic analysis was applied to derive individual concentration-effect relationships. For mechanical paw pressure a composite model consisting of an Emax model for the anti-hyperalgesic effect in combination with a linear model for the anti-nociceptive effect accurately described the data. The EC50 for the anti-hyperalgesic effect was 178+/-51 ng ml(-1) and the slope of the anti-nociceptive effect 0.055+/-0.008 g ml ng(-1). For the Von Frey Hair monofilament withdrawal threshold responders and non-responders were observed. Typically, in responders, full pain relief was observed at concentrations exceeding 100 ng ml(-1). The high plasma concentrations required for the anti-hyperalgesic effect relative to the receptor affinity are consistent with restricted transport of 5'dCPA to the site of action in the spinal cord and/or the brain.

Th2 shift in mononeuritis multiplex and increase of Th2 cells in chronic inflammatory demyelinating polyneuropathy: an intracellular cytokine analysis.

To elucidate the T helper 1 (Th1)/T helper 2 (Th2) balance in various inflammatory neuropathies, we measured the ratio of intracellular interferon-gamma (IFN-gamma)-positive to IL-4-positive cells (intracellular IFN-gamma/IL-4 ratio) by flow cytometry in peripheral blood CD4(+) T cells of 14 patients with mononeuritis multiplex (MNM), 12 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 10 patients with Guillain-Barré syndrome (GBS), 23 patients with neurodegenerative disorders and 36 healthy controls by intracellular labeling. The patients with MNM showed a significantly lower intracellular IFN-gamma/IL-4 ratio (P<0.05) and higher IL-4(+)/IFN-gamma(-) cell percentages (P<0.05) than the controls. The increase of IL-4(+)/IFN-gamma(-) cell percentages was especially prominent in MNM of unknown etiology (P<0.005). The patients with CIDP also showed significantly higher IL-4(+)/IFN-gamma(-) cell percentages (P<0.05) than the controls. The IL-4(+)/IFN-gamma(-) cell percentages were increased in some patients with GBS, but the difference was not significant compared with the controls. Thus, our results suggest that a Th2 shift is a characteristic of MNM and may play an important role in the development of the disease.