Investigation of oxidative stress in patients with multifocal motor neuropathy.

Background and purpose: Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. Methods: We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well. Results: MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Conclusion: Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.

[Diagnostics of autoimmune diseases]. / Diagnostik der Autoimmunerkrankungen.

Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of special and rare autoantibodies that otherwise often remain undetected. Standardisation of autoimmune diagnostics is still underway and requires joint efforts by laboratories, clinicians and industry.

Evidence that anti-muscarinic antibodies in Sjögren's syndrome recognise both M3R and M1R.

Inhibitory anti-muscarinic receptor type 3 (M3R) antibodies may contribute to the pathogenesis of Sjögren's syndrome (SS), and putative anti-M3R blocking antibodies in intravenous immunoglobulin (IVIg) have been suggested as a rationale for treatment with IVIg. We investigated the presence of subtype-specific anti-MR autoantibodies in healthy donor and SS sera using MR-transfected whole-cell binding assays as well as M1R and M3R peptide ELISAs. Control antibodies against the second extracellular loop of the M3R, a suggested target epitope, were induced in rabbits and found to be cross-reactive on the peptides M3R and M1R. The rabbit antibodies had neither an agonistic nor an antagonistic effect on M3R-dependent ERK1/2 signalling. Only one primary SS (out of 5 primary SS, 2 secondary SS and 5 control sera) reacted strongly with M3R transfected cells. The same SS serum also reacted strongly with M1R and M2R transfectants, as well as M1R and two different M3R peptides. Strong binding to M1R and low-level activities against M3R peptides were observed both in SS and control sera. IVIg showed a strong reactivity against all three peptides, especially M1R. Our results indicate that certain SS individuals may have antibodies against M1R, M2R and M3R. Our results also suggest that neither the linear M3R peptide nor M3R transfectants represent suitable tools for discrimination of pathogenic from natural autoantibodies in SS.

Topical application of the tumour necrosis factor-alpha antibody infliximab improves healing of chronic wounds.

The role of tumour necrosis factor-alpha (TNF-alpha) in wound healing is not clear. Elevated levels of TNF-alpha have been observed in fluids from chronic wounds and have been shown to decrease over time during the healing process. Therapeutic antibodies such as infliximab can inhibit TNF-alpha activity. In this case series, we applied infliximab topically to eight patients with chronic ulcers of more than 4-month durations. The ulcers had multifactorial aetiology, with chronic venous insufficiency being the most prominent factor. All the ulcers had failed to respond to any previous conventional treatment. Infliximab was applied repeatedly to ulcers either as a 10 mg/ml solution and covered with an adhesive sheet or as a gel formulation (0.45, 1, or 4.5 mg/g) under a hydrofiber dressing/adhesive sheet. Improvement was assessed by measuring the percentage of change in the ulcer surface area. Seven of the eight patients (12 of 14 ulcers) responded to treatment with infliximab. After 4 weeks of treatment, surface area was reduced by more than 50% in 6 of the 14 treated ulcers. Within 8 weeks, five ulcers completely healed, while another four were reduced by more than 75% in size. Chronic, therapy-resistant leg ulcers responded well to repeated topical administration of a solution or a gel containing the TNF-alpha antibody, infliximab. Randomised controlled studies should be conducted to further evaluate the effect of topical infliximab on chronic wound healing.