Oral mucosal manifestations of autoimmune skin diseases

Mustafa, Mayson; Porter, Stephen; Smoller, Bruce R.; Sitaru, Cassian

doi:10.1016/j.autrev.2015.06.005

Cited by 80 publications

(101 citation statements)

References 194 publications

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“…are present in patients with systemic lupus erythematosus and scleroderma, as well as organ-specific autoimmune disorders of skin, gastrointestinal tract, endocrine glands, and so forth, and many of these particular Igs are linked to distinct disease phenotypes (28,(43)(44)(45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Surolia

et al. 2017

The Journal of Immunology

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Autoimmunity has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the repertoire of autoantigens involved in this disease and the clinical relevance of these autoimmune responses are still being explored. Our initial discovery assays demonstrated that circulating and intrapulmonary vimentin levels are increased in IPF patients. Subsequent studies showed native vimentin induced HLA-DR–dependent in vitro proliferation of CD4 T cells from IPF patients and enhanced the production of IL-4, IL-17, and TGF-β1 by these lymphocytes in contrast to normal control specimens. Vimentin supplementation of IPF PBMC cultures also resulted in HLA-DR–dependent production of IgG with anti-vimentin specificities. Circulating anti-vimentin IgG autoantibody levels were much greater in IPF subjects from the University of Alabama at Birmingham (n = 102) and the University of Pittsburgh (U. Pitt., n = 70) than in normal controls. Anti-vimentin autoantibody levels in IPF patients were HLA biased and inversely correlated with physiological measurements of lung function (i.e., forced expiratory volumes and diffusing capacities). Despite considerable intergroup differences in transplant-free survival between these two independent IPF cohorts, serious adverse outcomes were most frequent among the patients within each population that had the highest anti-vimentin autoantibody levels (University of Alabama at Birmingham: hazard ratio 2.5, 95% confidence interval 1.2–5.3, p = 0.012; University of Pittsburgh: hazard ratio 2.7, 95% confidence interval 1.3–5.5, p = 0.006). These data show that anti-vimentin autoreactivity is prevalent in IPF patients and is strongly associated with disease manifestations. These findings have implications with regard to the pathogenesis of this enigmatic disease and raise the possibility that therapies specifically directed at these autoimmune processes could have therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Surolia

et al. 2017

The Journal of Immunology

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“…In several acquired autoimmune bullous skin diseases, the adaptive immune system targets self Ags in the skin BM zone that mediate epidermal-dermal adherence (Table 1) (reviewed in [173]. These disorders are generally diagnosed in older adults, and have a prominent autoantibody component that assists in diagnosis and contributes to pathogenesis.…”

Section: Autoimmune Dermatosesmentioning

confidence: 99%

Basement membranes and autoimmune diseases

Foster

2017

Matrix Biology

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Basement membrane components are targets of autoimmune attack in diverse diseases that destroy kidneys, lungs, skin, mucous membranes, joints, and other organs in man. Epitopes on collagen and laminin, in particular, are targeted by autoantibodies and T cells in anti-glomerular basement membrane glomerulonephritis, Goodpasture’s disease, rheumatoid arthritis, post-lung transplant bronchiolitis obliterans syndrome, and multiple autoimmune dermatoses. This review examines major diseases linked to basement membrane autoreactivity, with a focus on investigations in patients and animal models that advance our understanding of disease pathogenesis. Autoimmunity to glomerular basement membrane type IV is discussed in depth as a prototypic organ-specific autoimmune disease yielding novel insights into the complexity of anti-basement membrane immunity and the roles of genetic and environmental susceptibility.

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“…Oral ulcers are frequently chronic mucocutaneous lesions that affect up to 54% of patients with SLE [42, 43]. This clinical manifestation is characterized by high angiogenic activity and a loss of the epithelial and connective tissue in the oral mucosa [44, 45].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus

et al. 2017

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BackgroundSystemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE.MethodsA two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed.ResultsIn the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies (P FDR < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies.ConclusionsThe present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1345-6) contains supplementary material, which is available to authorized users.

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Oral mucosal manifestations of autoimmune skin diseases

Cited by 80 publications

References 194 publications

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Basement membranes and autoimmune diseases

Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus

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