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Autoimmune Mechanism (autoimmune + mechanism)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

The PTPN22 -1858C>T (R620W) functional polymorphism is associated with generalized vitiligo in the Romanian population

PIGMENT CELL & MELANOMA RESEARCH, Issue 2 2008
Greggory S. LaBerge
Summary Generalized vitiligo is an autoimmune disorder of the skin in which autoimmune-mediated destruction of melanocytes leads to depigmented patches of skin and overlying hair. The 1858C>T (R620W) functional polymorphism of the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (Lyp), has been associated with susceptibility to a number of autoimmune disorders, including generalized vitiligo. The aim of this study was to test genetic association of the PTPN22 1858C>T variant and generalized vitiligo in a Romanian case-control cohort. We observed significant association of generalized vitiligo with the 1858T risk allele of PTPN22 [P = 0.0138; OR = 2.92 (1.21,7.03)], with significantly different distribution of PTPN22 1858C>T genotypes in cases versus controls [P = 0.036; OR = 2.69 (1.07,6.80)]. Our results provide evidence that the PTPN22 1858T allele contributes to risk of generalized vitiligo in European Caucasian populations, and underscores the importance of a genetically mediated autoimmune mechanism in the pathogenesis of vitiligo. [source]

Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 1 2010
Nicholas Simpson
Objective In the sanroque mouse model of lupus, pathologic germinal centers (GCs) arise due to increased numbers of follicular helper T (Tfh) cells, resulting in high-affinity anti,double-stranded DNA antibodies that cause end-organ inflammation, such as glomerulonephritis. The purpose of this study was to examine the hypothesis that this pathway could account for a subset of patients with systemic lupus erythematosus (SLE). Methods An expansion of Tfh cells is a causal, and therefore consistent, component of the sanroque mouse phenotype. We validated the enumeration of circulating T cells resembling Tfh cells as a biomarker of this expansion in sanroque mice, and we performed a comprehensive comparison of the surface phenotype of circulating and tonsillar Tfh cells in humans. This circulating biomarker was enumerated in SLE patients (n = 46), Sjögren's syndrome patients (n = 17), and healthy controls (n = 48) and was correlated with disease activity and end-organ involvement. Results In sanroque mice, circulating Tfh cells increased in proportion to their GC counterparts, making circulating Tfh cells a feasible human biomarker of this novel mechanism of breakdown in GC tolerance. In a subset of SLE patients (14 of 46), but in none of the controls, the levels of circulating Tfh cells (defined as circulating CXCR5+CD4+ cells with high expression of Tfh-associated molecules, such as inducible T cell costimulator or programmed death 1) were increased. This cellular phenotype did not vary with time, disease activity, or treatment, but it did correlate with the diversity and titers of autoantibodies and with the severity of end-organ involvement. Conclusion These findings in SLE patients are consistent with the autoimmune mechanism in sanroque mice and identify Tfh effector molecules as possible therapeutic targets in a recognizable subset of patients with SLE. [source]

Hypocretin/orexin and narcolepsy: new basic and clinical insights

ACTA PHYSIOLOGICA, Issue 3 2010
S. Nishino
Abstract Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain,Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ,narcolepsy with cataplexy' and ,narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. [source]

Vitiligo Treatment in Childhood: A State of the Art Review

PEDIATRIC DERMATOLOGY, Issue 5 2010
Marion Eunice B. Tamesis M.D.
Approximately half of the affected individuals develop the disease before adulthood. Etiologic hypotheses for vitiligo include biochemical, neural and autoimmune mechanisms. The most compelling of these suggests a combination of genetic and immunologic factors that result in an autoimmune melanocyte destruction. We reviewed studies carried out on various treatment modalities used in childhood vitiligo. Topical corticosteroids were found to have excellent repigmentation rates, whereas calcineurin inhibitors have comparable efficacy and a better safety profile compared with topical corticosteroids. These two groups of topical medications are good first-line treatment modalities for localized vitiligo. For the treatment of generalized vitiligo, phototherapy has excellent efficacy. Narrow-band ultraviolet B (UVB) has better overall repigmentation rates and safety profile than either topical or oral psoralens and ultraviolet A (PUVA). Other treatment modalities may be considered depending on a patient's specific condition, such as surgical options and depigmentation. With adequate sun protection, the option of no treatment with or without corrective camouflage, is an innocuous alternative to any of these treatment modalities. [source]