Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): I. Marie, J-F. Gehanno, M. Bubenheim, A-B. Duval-Modeste, P. Joly, S. Dominique, P. Bravard, D. Noël, A-F. Cailleux, J. Weber, P. Lagoutte, J. Benichou, H. Levesque, J-P. Goullé
Objective.This case control study assessed: the relationship of systemic sclerosis (SSc) related to exposure to heavy metals, the risk of SSc related to occupational exposure in male and female patients.MethodsFrom 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habits matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS).ResultsSSc patients exhibited higher median levels of the following metals: antimony (p=0.001), cadmium (p=0.0003), lead (p=0.02), mercury (p=0.02), molybdenum (p=0.04), palladium (p<0.001) and zinc (p=0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p=0.008) and platinum (p=0.04) in male patients; and 2) antimony (p=0.02), cadmium (p=0.001), lead (p=0.03), mercury (p=0.03), palladium (p=0.0003) and zinc (p=0.0001) in female patientsConclusionThe results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients" gender.



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Inflammatory eye disease: pre-treatment assessment of patients prior to commencing immunosuppressive and biologic therapy: Recommendations from an expert committee

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): Denis Wakefield, Peter McCluskey, Gerhild Wildner, Stephan Thurau, Gregory Carr, Soon-Phaik Chee, John Forrester, Andrew Dick, Bernard Hudson, Susan Lightman, Justine Smith, Ilknur Tugal-Tutkun
AimTo outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy.MethodThe approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease.ConclusionWe recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects.



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Gender balance in patients with systemic lupus erythrematosus

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): Audrey A Margery-Muir, Christine Bundell, Delia Nelson, David M Groth, John D Wetherall
Factors are reviewed that contribute to the contemporary view of a disproportionate prevalence and incidence SLE in females. Recent studies on the epidemiology of SLE report that global Incidences and prevalences of SLE for Caucasian and Black populations are of the order of 5.5 and 13.1 per year and 81 and 212 per 100,000 persons respectively. Both parameters displayed age dependent variation over a 90-year lifespan. The female to male (F:M) incidence of SLE varied with age, being approximately 1 during the first decade of life, followed by a sharp increase to 9 during the 4th decade, thence declining in subsequent decades before an increase during the 7th or 8th decades. A cognate review of SLE diagnosis in neonates revealed a F:M ratio of ≈1.2, consistent with the epidemiology review and the sporadic nature of SLE. Notional estimates of disease duration showed a steady increase from a base level for both males and females. The linear trend line for males was always lower than the trend line for females, supporting clinical experience that SLE is a more severe disease in males. Over a 14-year interval ending in 2012, the notional duration of SLE increased from 10 to 15years to 20–25years, probably reflecting advances in diagnosis and clinical practice.A metastudy of SLE concordance in twins revealed a 75% discordance in monozygotic twins compared to a 95% discordance in dizygotic twins confirming the importance of environmental factors in susceptibility to SLE. The elevated discordance in dizygotic SLE twins (and between siblings) suggests a role for the intrinsic genomic sexual dimorphism due to divergence of Y chromosome regulatory loci from their X chromosome homologues due to lack of recombination of mammalian sex chromosomes over evolutionary time.Estimates were made of the incidences of SLE in males and females based on population data for nine autosomal deficiency loci of major effect, plus expected male prevalence associated with Kleinfelter's syndrome and female prevalence associated with Triple X syndrome. These genetic abnormalities accounted for ≈4% of female and ≈23% of male Caucasoid prevalence and for SLE resulting in a F:M ratio of ≈0.17. It may be deduced therefore that the impressive preponderance of SLE in females arises from a combination of environmental triggers and susceptibility loci of relatively small effect acting between the interval from the mini-puberty of childhood to the peak of reproductive adulthood. It is in this cohort of females, and especially in the black population, that combinations of loci of minor effect acting together with environmental factors initiate defective apoptosis resulting in consequential autoimmune disease especially SLE. We postulate that because apoptosis is itself a very complex process, and defective apoptosis is an important contributor to SLE, there will be many combinations of susceptibility loci and environmental stimuli that can result in SLE (and other autoimmune disease(s)), of varying severity.



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Characterization of isolated retinal vasculitis. Analysis of a cohort from a single center and literature review

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): Laura Pelegrín, José Hernández-Rodríguez, Gerard Espinosa, Víctor Llorenç, Maite Sainz-de-la-Maza, José R. Fontenla, José A. Martínez, Maria C. Cid, Alfredo Adán
IntroductionIsolated retinal vasculitis (IRV) is an inflammatory condition of unknown etiology confined to the retinal vessels. In contrast to secondary retinal vasculitis (RV), IRV has not been well characterized.ObjectiveTo describe and characterize isolated forms of RV.MethodsWe performed a retrospective review (2006–2016) of IRV patients from a multidisciplinary Uveitis Unit. RV diagnosis was based on funduscopic and fluorescein angiography findings. To distinguish between secondary RV and IRV, evaluations included clinical assessment, laboratory inflammatory, autoimmune and microbiological markers and chest radiography. Ophthalmological features at disease onset, therapeutic interventions, ocular relapses, visual outcomes and laboratory findings were recorded. Our cases were subsequently compared with those from a literature review.ResultsAmong 192 patients with RV, 11 (5.7%) were diagnosed with IRV. Seven patients with initially presumed IRV were reclassified as secondary after further evaluation. IRV generally affected adult women. Bilateral ocular involvement and retinal phlebitis were common findings. 72% of patients presented with visual loss, which was severe in 27%. Treatments used included systemic glucocorticoids (82%), additional immunosuppressive agents (27%), intravitreal therapy (37%), panretinal photocoagulation (37%) and pars plana vitrectomy (26%). The annual relapse rate was 0.46. Although final visual acuity was considered good in 86%, 45% experienced worsening and only 27% improved.ConclusionsIRV is a rare sight-threatening condition. Despite intensive local and systemic immunosuppressive treatment, visual improvement is observed in only 27% of cases. When IRV is suspected, a differential diagnosis excluding a systemic disease is always warranted. A multidisciplinary approach and a guided clinical, laboratory and imaging evaluation has proven to be useful to distinguish retinal single-organ vasculitis from secondary forms of RV.



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Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

Publication date: Available online 28 January 2017
Source:Autoimmunity Reviews
Author(s): Grazyna Adamus
Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD.



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Microglia in CNS development: shaping the brain for the future

Publication date: Available online 28 January 2017
Source:Progress in Neurobiology
Author(s): Coralie-Anne Mosser, Sofia Baptista, Isabelle Arnoux, Etienne Audinat
Microglial cells are the resident macrophages of the central nervous system (CNS) and are mainly known for their roles in neuropathologies. However, major recent developments have revealed that these immune cells actively interact with neurons in physiological conditions and can modulate the fate and functions of synapses. Originating from myeloid precursors born in the yolk sac, microglial cells invade the CNS during early embryonic development. As a consequence they can potentially influence neuronal proliferation, migration and differentiation as well as the formation and maturation of neuronal networks, thereby contributing to the entire shaping of the CNS. We review here recent evidence indicating that microglial cells are indeed involved in crucial steps of the CNS development, including neuronal survival and apoptosis, axonal growth, migration of neurons, pruning of supernumerary synapses and functional maturation of developing synapses. We also discuss current hypotheses proposing that diverting microglial cells of their physiological functions, by promoting the expression of an immune phenotype during development, may be central to neurodevelopmental disorders such as autism, schizophrenia and epilepsy.



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Practice makes perfect: Performance optimisation in ‘arboreal’ parkour athletes illuminates the evolutionary ecology of great ape anatomy

Publication date: February 2017
Source:Journal of Human Evolution, Volume 103
Author(s): Lewis G. Halsey, Samuel R.L. Coward, Robin H. Crompton, Susannah K.S. Thorpe
An animal's size is central to its ecology, yet remarkably little is known about the selective pressures that drive this trait. A particularly compelling example is how ancestral apes evolved large body mass in such a physically and energetically challenging environment as the forest canopy, where weight-bearing branches and lianas are flexible, irregular and discontinuous, and the majority of preferred foods are situated on the most flexible branches at the periphery of tree crowns. To date the issue has been intractable due to a lack of relevant fossil material, the limited capacity of the fossil record to reconstruct an animal's behavioural ecology and the inability to measure energy consumption in freely moving apes. We studied the oxygen consumption of parkour athletes while they traversed an arboreal-like course as an elite model ape, to test the ecomorphological and behavioural mechanisms by which a large-bodied ape could optimize its energetic performance during tree-based locomotion. Our results show that familiarity with the arboreal-like course allowed the athletes to substantially reduce their energy expenditure. Furthermore, athletes with larger arm spans and shorter legs were particularly adept at finding energetic savings. Our results flesh out the scanty fossil record to offer evidence that long, strong arms, broad chests and a strong axial system, combined with the frequent use of uniform branch-to-branch arboreal pathways, were critical to off-setting the mechanical and energetic demands of large mass in ancestral apes.



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