Rare Diseases Symptoms Automatic Extraction

Cytokines as genetic modifiers in K5-/- mice and in human epidermolysis bullosa simplex.

[epidermolysis bullosa simplex]

Epidermolysis bullosa simplex (EBS) is a skin disorder caused by fully-penetrant mutations in the keratin genes KRT5 and KRT14, leading to extensive cytolysis and cell fragility of basal keratinocytes. EBS is subject to environmental conditions and displays high intra- and interfamilial variability, suggesting modifying loci. Here, we demonstrate that upregulation of certain cytokines accompanies mutations in keratin 5 (K5) but not in keratin 14 (K14). We find for the first time that cytokines macrophage chemotactic protein (MCP)-1/[chemokine (C-C motif) ligand 2] (CCL2), macrophage inflammatory protein (MIP)-3beta/CCL19 and MIP-3alpha/CCL20, all regulated by nuclear factor kappa B (NFkappaB) and involved in the recruitment, maturation, and migration of Langerhans cells (LCs) in the epidermis, are upregulated in the skin of K5(-/-), but not of K14(-/-) mice. In neonatal K5(-/-) epidermis, the number of LCs was increased two-fold. At the same time, tumor necrosis factor alpha (TNFalpha) remained unaltered, demonstrating the specificity of that process. Most remarkably, enhanced LC recruitment within the epidermis was found in five EBS patients carrying mutations in the KRT5 gene but not in EBS patients with KRT14 gene mutations. In agreement with the NFkappaB-dependent regulation of these cytokines, we found a decrease in p120-catenin in the basal epidermis of K5(-/-) mice. These data provide the first explanation for distinct, keratin-type-specific genotype-phenotype correlations in EBS and represent a rationale to investigate gene loci affecting skin pathology in EBS.

Diseases presenting "first time" symptom

  • achondroplasia
  • acute rheumatic fever
  • adrenal incidentaloma
  • adrenomyeloneuropathy
  • alpha-thalassemia
  • aniridia
  • aromatase deficiency
  • canavan disease
  • carcinoma of the gallbladder
  • cholangiocarcinoma
  • classical phenylketonuria
  • congenital adrenal hyperplasia
  • congenital toxoplasmosis
  • cowden syndrome
  • cushing syndrome
  • cutaneous mastocytosis
  • dedifferentiated liposarcoma
  • dentin dysplasia
  • dentinogenesis imperfecta
  • dracunculiasis
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • erdheim-chester disease
  • erythropoietic protoporphyria
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • esophageal squamous cell carcinoma
  • fabry disease
  • familial mediterranean fever
  • gm1 gangliosidosis
  • harlequin ichthyosis
  • heparin-induced thrombocytopenia
  • hirschsprung disease
  • hodgkin lymphoma, classical
  • holt-oram syndrome
  • hydrocephalus with stenosis of the aqueduct of sylvius
  • junctional epidermolysis bullosa
  • kabuki syndrome
  • kallmann syndrome
  • liposarcoma
  • locked-in syndrome
  • lymphangioleiomyomatosis
  • malignant atrophic papulosis
  • megacystis-microcolon-intestinal hypoperistalsis syndrome
  • monosomy 21
  • neuralgic amyotrophy
  • oculocutaneous albinism
  • oligodontia
  • omenn syndrome
  • oral submucous fibrosis
  • papillon-lefèvre syndrome
  • pendred syndrome
  • phenylketonuria
  • primary effusion lymphoma
  • primary hyperoxaluria type 1
  • severe combined immunodeficiency
  • sneddon syndrome
  • triple a syndrome
  • trochlear dysplasia
  • von hippel-lindau disease
  • waldenström macroglobulinemia
  • well-differentiated liposarcoma
  • werner syndrome
  • wiskott-aldrich syndrome
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy
  • zellweger syndrome

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