Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The murine MHC class II variant I-Ad confers susceptibility to herpes simplex virus (HSV)-induced keratitis and relative protection against type 1 diabetes mellitus. The association to these autoimmune diseases appears to be largely determined by the peptide sidechain specificity of the P9 pocket, which we therefore have analyzed in detail. Assessment of T-cell responses and I-Ad binding capacity of position 446-substituted analogs of an IgG2a allotype b (IgG2a(b)) heavy chain peptide demonstrates that engagement of the P9 pocket is crucial for effective peptide presentation. Sidechain size rather than charge decides the capacity to engage the P9 pocket. Thus, small, uncharged sidechains are accepted, whereas acidic and aromatic amino acids as well as lysine and arginine are disfavored. The specificity of the P9 pocket of I-Ad (serine beta57) is distinct from that of the diabetes-associated I-Ag7 (aspartic acid beta57), supporting the contention that the polymorphism at residue beta57 influences diabetes susceptibility via P9-specific effects on the repertoires of self peptides presented to T cells. Furthermore, the data rationalize the susceptibility to HSV-induced keratitis conferred by the a and the protection conferred by the b allotypes of the IgG2a heavy chain. Keratitogenic T cells, which cross-react with the viral UL6 protein and a corneal antigen, are silenced in IgG2a(b) mice because of antigenic mimicry with gamma2a(b) 435-451. Our finding that the lysine P9 residue of the corresponding gamma2a(a) allopeptide precludes high-affinity binding to I-Ad indicates that the susceptibility of IgG2a(a) mice reflects inefficient thymic presentation of autologous IgG2a and thus failure to purge the T-cell repertoire of the pathogenic clones.
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PMID:The P9 peptide sidechain specificity of I-Ad. 1065 74

A 26-year-old Japanese woman was referred to our hospital with generalized hyperkeratosis associated with keratitis and a hearing defect. The patient was born from nonconsanguineous parents. Her skin was moderately hyperkeratotic at birth. During childhood, the thickness of the skin increased progressively. Bilateral sensorineural deafness was recognized at the age of 3 years. Visual disturbance was noted in later childhood, and corneal transplantations to the right eye were performed twice at the age of 16 and 25 years, but did not improve her visual acuity. There was no family history of similar disease. On physical examination, the patient showed erythematous, keratotic, scaly plaques on the cheeks, auricles, and perioral area (Fig. 1a). A grainy, spiculated, hyperkeratotic papillomatosis was particularly marked on the palms and the edge of the feet (Fig. 1b,c). The nails were slight hypertrophic, but not dystrophic. Ophthalmologic examination revealed the loss of eyebrows and eyelashes and hyperkeratotic lesions of the eyelids (Fig. 1d). Corneal opacification was observed in the right eye. Conjunctivitis and blepharitis with photophobia were also observed in both eyes (Fig. 1d,e). A skin biopsy specimen from the right lower thigh showed basket-wave hyperkeratosis and papillomatosis of the epidermis. Hyperkeratotic plugs were not observed (Fig. 1f). Laboratory data, including complete blood cell count, sedimentation rate, immunoglobulins and transaminases, urea, cholesterol, and triglycerides were normal. With informed consent, genomic DNA was extracted from blood samples. The complete open reading frame of the GJB2 gene was polymerase chain reaction amplified and sequenced. A transition mutation (148G --> A) was detected, resulting in a putative amino acid change from aspartic acid to asparagine at codon 50 (Fig. 2). The mutation was not present in her parents or two siblings. These clinical, pathologic, and genetic data supported the diagnosis of keratitis-ichthyosis-deafness syndrome.
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PMID:A case of keratitis-ichthyosis-deafness (KID) syndrome. 1744 83

Human adenovirus (HAdV) infection of the human eye, in particular serotypes 8, 19 and 37, induces the formation of corneal subepithelial leukocytic infiltrates. Using a unique mouse model of adenovirus keratitis, we studied the role of various virus-associated molecular patterns in subsequent innate immune responses of resident corneal cells to HAdV-37 infection. We found that neither viral DNA, viral gene expression, or viral replication was necessary for the development of keratitis. In contrast, empty viral capsid induced keratitis and a chemokine profile similar to intact virus. Transfected viral DNA did not induce leukocyte infiltration despite CCL2 expression similar to levels in virus infected corneas. Mice without toll-like receptor 9 (Tlr9) signaling developed clinical keratitis upon HAdV-37 infection similar to wild type mice, although the absolute numbers of activated monocytes in the cornea were less in Tlr9(-/-) mice. Virus induced leukocytic infiltrates and chemokine expression in mouse cornea could be blocked by treatment with a peptide containing arginine glycine aspartic acid (RGD). These results demonstrate that adenovirus infection of the cornea induces chemokine expression and subsequent infiltration by leukocytes principally through RGD contact between viral capsid and the host cell, possibly through direct interaction between the viral capsid penton base and host cell integrins.
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PMID:Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis. 2041 41