Individual mechanisms underlying peripheral nerve damage when exposed to metallic mercury

Introduction. There is a lack of knowledge of the pathophysiological mechanisms that form peripheral nerve disorders in mercury lesions of professional origin. The study aims to reveal the mechanisms underlying peripheral nerve damage in the long-term post-contact period of chronic mercury intoxication (CMI). Materials and methods. Fifty-one people had the diagnosis of a long-term period of CMI. The post-contact period was 8.5±2.6 years. The authors compared the results with a control group of 26 healthy men who had no contact with toxic substances. Stimulating electroneuromyography was performed. We studied the body systems that could contribute to the formation of disorders in the peripheral nerves. Changes in peripheral hemodynamics were studied using reovasography. The content of autoantibodies, neuron-specific enolase, serotonin, histamine, catecholamines (epinephrine, dopamine), metanephrine, and neurotrophin-3 was reviewed. The content of ceruloplasmin, secondary products of lipid peroxidation processes, reduced glutathione, the activity of superoxide dismutase and the content of nitric oxide levels were determined. Results. The study established pathogenetic structural links of peripheral nerve disorders. The autoimmune process's role was to increase the range of antibodies to the MAG protein and increase the level of antibodies to DNA. Violations of elastic-tonic properties of peripheral vessels could be associated with the functional state of motor axons. The increased content of neurotransmitters is related to the state of peripheral blood circulation; the most pronounced changes were on the legs, which could contribute to the occurrence and maintenance of vasoconstriction. The role of oxidative stress in the formation of demyelinating disorders in patients' peripheral nerves in the long-term period of CRI is possible. Conclusion. Neuroimmunological processes has an essential role in the development of peripheral nerve demyelination was shown, which consists in an increase in the content of antibodies to the MAG protein expressed on Schwann cells of peripheral nerves and in an increase in the level of antibodies to DNA involved in the formation of demyelinating changes when exposed to metallic mercury. The revealed pathological changes in the state of the peripheral blood circulation, characterized by a violation of the vessels' elastic-tonic properties, leading to demyelination of motor axons in patients in the long-term period of CMI. The increased content of neurotransmitters in the examined is of great importance in the state of peripheral circulation. Pronounced changes in blood circulation are established on the lower extremities, which may be associated with the predominance of α-adrenergic receptors in the arterial bed and may contribute to the occurrence and maintenance of vasoconstriction in the legs. The relationship between changes in indicators of oxidative stress, consisting of a decrease in the value of superoxide dismutase and reduced glutathione, and the formation of demyelinating disorders of peripheral nerves in patients in the long-term period of CMI has been proved.

Autoimmunity and autoinflammation in pathogenesis of immunoinflammatory diseases

Rheumatic diseases relate to the group of the immunoinflammatory diseases (IID), in pathogenesis of which have a value both autoimmune and autoinflammatory processes. Aim.To present the heterogeneous pathogenesis of inflammation in IID. Materials and methods.It is inspected 260 patients (pts) with IID: 242 pts with systemic autoimmune diseases (SAD): 65 systemic lupus erythematosis, 50 systemic sclerosis, 127 systemic vasculitides (SV) and 18 patients with autoinflammatory diseases (AID): 8 Behcets disease, 2 periodic disease, 5 familial cold fever, 2 idiopathic lobular panniculitis and 1 relapsing polychondritis. Is carried out a study of complement, antigen of von Willebrand factor (FW:AG), antinuclear antibodies, antibodies to DNA, anti-endothelial antibodies, antibodies to topoizomeraze I (anti-Scl-70), antineutrophilic cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aCL IgG and aCL IgM), cryoglobulins, VS, CRP. Results.SAD were characterized by the synthesis of wide antibodies spectrum. As the basic serological marker at the screening it follows to consider antinuclear antibodies (75%). Practically in all groups it took place hypcomlemetemia with reduction of C3 and C4 complement. With systemic lupus erythematosis are revealed antibodies to DNA (71%), with ANCA-associated SV-ANCA (94%), aKL (14%); with SSD aScl-70 (17%). At Wegener granulomatosis ANCA are determined in 94% patients in the active stage. It is noted correlation ANCA with the index of the clinical activity of vasculitis. In the remaining SV groups ANCA were separated in the single cases. Cryoglobulins are noted in all patients with cryoglobulinemic vasculitis. aCL IgG and aCL IgM were the markers of antiphospholipid syndrome. Аnti-endothelial antibodies had significant oscillation spectrum. High indices FW:AG are noted with all above nosologic forms indicated, especially with Wegener granulomatosis and vasculitis hemorrhagic. Among the laboratory tests of inflammatory activity should be considered the determination of VS, CRP and FV:AG, which is also considered the marker of vascular wall defeat. Is given clinical characteristic and changes in the laboratory indices at AID: Conclusion.Isolation from the group IID of patients with AID serves as indication for a genetic study of this contingent with the approval of use for their treatment of biological therapy. Isolation from the group SAD patients with AID serves as indication for a genetic study of this contingent with the approval of use for their treatment of biological therapy.

AB0397 LUPUS FATIGUE PROBLEMS IN THE RUSSIAN COHORT OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (RENAISSANCE).

Background:Objectives:To determine the dependency of fatigue from SLE activity, irreversible organ damage and HRQoL in SLE patients of the Renaissance cohort.Methods:328 Russian SLE patients were enrolled in the study (M/F 30/298) who fulfilled SLICC 2012 criteria. The SLEDAI 2K activity, SLICC damage index, Facit Fatigue scale, and health related quality of life (HRQol) using the LupusQol questionnaire were evaluated.Results:Based on the Facit Fatigue scale scores fatigue was verified in 148 (45%) out of 328 patients with SLE. Following lupus fatigue status patients were divided into two groups - 148 and 168 patients respectively. The groups were perfectly matched in terms of age, duration of the disease, duration of GCs therapy, and damage scores (Table 1)Characteristicsmean (SD)Patients with lupus fatigue(n=148)Patients without lupus fatigue(n=168)P(Mann-Whitney)Age in years35,31±12,0333,68±10,680,13Disease durationin in years9,57±9,4710,1±9,170,6Duration of glucocorticoid therapy in month72,81±715879,43±75,980,6SLICC DaI, score1,55±1,371,69±1,230,44C3 Mu\ml0,88±0,330,87±0,310,75C4 Mu\ml0,15±0,120,16±0,140,36ANF, hep2641± 453550± 4020,4Fatigue scores by the Facit fatigue scale25,16±6,5842,43±4,560,000The SLEDAI 2K activity scores were significantly higher in the group with lupus fatigue - 9.6±6.0 vs 6.7±4.2 (p=0.01) as compared to values in the group without fatigue, as well as the level of antibodies to DNA (p=0.02), 110.2±34.2 and 82.3±20.5, respectively.There was a significant decrease in HRQoL in patients with lupus fatigue based on scores in all eight scales of the questionnaire (p=0.00),Figure 1.Comparative assessment of HRQoL using the LupusQol questionnaire in 328 SLE patients with and without fatigue.Conclusion:Almost half (45%) SLE patients in the Russian cohort experience fatigue. It is associated with disease activity on the SLEDAI 2k scale and high levels of antibodies to DNA. All patients experiencing lupus fatigue have significantly worse HRQoL based on scores in all eight scales of the questionnaire LupusQol.Disclosure of Interests:None declared

International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I

The indirect immunofluorescence assay (IFA) on HEp-2 cells is the reference method for autoantibody screening. The HEp-2 IFA pattern provides useful information on the possible autoantibodies in the sample. The International Consensus on Antinuclear Antibody Patterns (ICAP) initiative seeks to define and harmonize the nomenclature of HEp-2 IFA patterns. The most relevant and usual patterns have been assigned an alphanumeric code from anti-cell (AC)-1 to AC-28 and were organized into a classification algorithm (www.ANApatterns.org). The systemic sclerosis-associated autoantibodies to DNA topoisomerase I (Topo I) produce a peculiar composite 5-element HEp-2 IFA pattern (Topo I-like pattern) comprising the staining of the nucleus, metaphase chromatin plate, nucleolar organizing region, cytoplasm and nucleolus. In a recent assessment of the European Consensus Finding Study Group on autoantibodies, a well-defined anti-Topo I sample was blindly analyzed and classified according to ICAP AC patterns by 43 participant laboratories across Europe. There were wide variations among these laboratories in reporting nuclear, nucleolar and cytoplasmic patterns, indicating the inadequacy of the existing AC patterns to report the Topo I-like pattern. Several ICAP member laboratories independently demonstrated the overall consistency of the HEp-2 IFA Topo I-like pattern using HEp-2 slides from different manufacturers. The ICAP committee reviewed 24 candidate images and selected the four most representative images to be available on the ICAP website. The proper recognition of the AC-29 pattern should trigger suspicion of the presence of anti-Topo I antibodies, which may engender appropriate analyte-specific reflex tests to confirm the autoantibody specificity.