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1.
Hum Immunol ; 82(8): 593-599, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33875297

ABSTRACT

Atopic dermatitis (AD) is a common immune-medicated skin disease. Previous studies have explored the relationship between Human Leukocyte Antigen (HLA) allelic variation and AD with conflicting results. The aim was to examine HLA Class I genetic variation, specifically peptide binding groove variation, and associations with AD. A case-control study was designed to evaluate HLA class I allelic variation and binding pocket polymorphisms, using next generation sequencing on 464 subjects with AD and 388 without AD. Logistic regression was used to evaluate associations with AD by estimating odds ratios (95% confidence intervals). Significant associations were noted with susceptibility to AD (B*53:01) and protection from AD (A*01:01, A*02:01, B*07:02 and C*07:02). Evaluation of polymorphic residues in Class I binding pockets revealed six amino acid residues conferring protection against AD: A9F (HLA-A, position 9, phenylalanine) [pocket B/C], A97I [pocket C/E], A152V [pocket E], A156R [pocket D/E], B163E [pocket A] and C116S [pocket F]. These findings demonstrate that specific HLA class I components are associated with susceptibility or protection from AD. Individual amino acid residues are relevant to protection from AD and set the foundation for evaluating potential HLA Class I molecules in complex with peptides/antigens that may initiate or interfere with T-cell responses.


Subject(s)
Dermatitis, Atopic/genetics , Genetic Predisposition to Disease , Genetic Variation , Histocompatibility Antigens Class I/genetics , Alleles , Case-Control Studies , Dermatitis, Atopic/diagnosis , Gene Frequency , Genetic Association Studies , Genotype , Histocompatibility Antigens Class I/chemistry , Humans , Models, Molecular , Odds Ratio , Polymorphism, Single Nucleotide , Protein Conformation , Sequence Analysis, DNA , Structure-Activity Relationship
2.
Br J Dermatol ; 165(2): 302-10, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21466536

ABSTRACT

BACKGROUND: A clear-cut need exists for safe and effective alternatives to the use of isotretinoin in severe acne. Lack of data regarding the specifics of isotretinoin's mechanism of action has hampered progress in this area. Recently, the protein neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a mediator of the apoptotic effect of isotretinoin on sebocytes. OBJECTIVES: To establish further the clinical relevance of NGAL and to elucidate the factors that induce NGAL expression in sebocytes. METHODS: Methods were developed to isolate and quantify skin-surface levels of NGAL from normal subjects and patients with acne undergoing treatment with isotretinoin. RESULTS: Patients with acne were found to have higher skin levels of NGAL compared with normal subjects. Studies in SEB-1 sebocytes indicate that NGAL expression is increased in response to Propionibacterium acnes and interleukin (IL)-1ß. In patients, isotretinoin increases NGAL levels by 2·4-fold on the skin surface and this increase precedes decreases in sebum and P. acnes counts. CONCLUSIONS: These data support the hypothesis that NGAL is an important mediator of the early effects of isotretinoin on the sebaceous glands and provide insights into the mechanisms that regulate NGAL expression in the skin.


Subject(s)
Acne Vulgaris/drug therapy , Acute-Phase Proteins/metabolism , Dermatologic Agents/therapeutic use , Isotretinoin/therapeutic use , Lipocalins/metabolism , Proto-Oncogene Proteins/metabolism , Skin/metabolism , Acne Vulgaris/metabolism , Adolescent , Adult , Cells, Cultured , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Humans , Interleukin-1beta/pharmacology , Interleukin-8/metabolism , Lipocalin-2 , Propionibacterium acnes/isolation & purification , Propionibacterium acnes/metabolism , Sebaceous Glands/cytology , Sebaceous Glands/metabolism , Skin/microbiology , Young Adult
3.
Pediatr Dermatol ; 18(3): 234-7, 2001.
Article in English | MEDLINE | ID: mdl-11438006

ABSTRACT

We report an instance of congenital granular cell tumors localized to the arm of a female infant. While granular cell tumors are well described during infancy as congenital epulis of the oral cavity, this case is unusual in both its location and histologic characteristics. The lesions, located around the antecubital fossa, were comprised of CD34-positive, S-100-negative granular cells. In addition, there were numerous eccrine glands in the upper dermis. The salient features of the case are discussed and reviewed in the context of the literature pertaining to this unusual entity.


Subject(s)
Granular Cell Tumor/congenital , Skin Neoplasms/congenital , Arm , Female , Follow-Up Studies , Granular Cell Tumor/pathology , Humans , Infant , Infant, Newborn , Remission, Spontaneous , Skin/pathology , Skin Neoplasms/pathology
4.
Pediatr Dermatol ; 18(2): 135-7, 2001.
Article in English | MEDLINE | ID: mdl-11358555

ABSTRACT

Congenital self-healing reticulohistiocytosis (CSHR) represents the benign end of the spectrum of Langerhans cell histiocytoses, with spontaneous resolution of lesions within the first year of life. However, involvement of organ systems other than the skin has been described occasionally and recurrence of disease at sites distant from the skin has been documented. We report a case of CSHR with eye involvement that spontaneously resolved concurrent with resolution of skin lesions. Because multiple organ systems can be involved and recurrences are possible, long-term follow-up of these patients is indicated.


Subject(s)
Eye Diseases/pathology , Histiocytosis, Non-Langerhans-Cell/pathology , Antigens, CD1/analysis , Diagnosis, Differential , Female , Histiocytosis, Non-Langerhans-Cell/congenital , Histiocytosis, Non-Langerhans-Cell/metabolism , Humans , Immunohistochemistry , Infant, Newborn , Remission, Spontaneous , S100 Proteins/analysis , Skin/chemistry , Skin/pathology
5.
Arch Dermatol ; 131(5): 571-3, 1995 May.
Article in English | MEDLINE | ID: mdl-7741544

ABSTRACT

BACKGROUND AND DESIGN: Immunofluorescence detection of stippled IgA in dermal papillae has been considered the gold standard in the diagnosis of dermatitis herpetiformis (DH). We have developed an immunohistochemical technique using the avidin-biotin-peroxidase complex that is equally effective as direct immunofluorescence in detecting IgA. We retrospectively studied 43 paraffin-embedded biopsy specimens obtained from patients with DH and a variety of other diseases for the presence of IgA along the basement membrane zone. RESULTS: Eleven immunofluorescence-proved cases of DH were found positive for IgA with the avidin-biotin-peroxidase method. One biopsy specimen originally classified as DH was identified and reclassified as linear IgA bullous disease based on the immunoperoxidase findings. All the samples that were positive on direct immunofluorescence were positive with the avidin-biotin-peroxidase method. Control samples of bullous pemphigoid, discoid lupus erythematosus, pemphigus vulgaris, and dermatitis were all negative for IgA deposition. CONCLUSION: The diagnosis of DH on formalin-fixed tissue is possible with the use of an avidin-biotin-peroxidase method, which is convenient and cost-effective.


Subject(s)
Dermatitis Herpetiformis/diagnosis , Immunoenzyme Techniques , Immunoglobulin A/analysis , Avidin , Basement Membrane/immunology , Basement Membrane/pathology , Biopsy , Biotin , Dermatitis/diagnosis , Dermatitis/immunology , Dermatitis/pathology , Dermatitis Herpetiformis/immunology , Dermatitis Herpetiformis/pathology , Fluorescent Antibody Technique , Humans , Lupus Erythematosus, Discoid/diagnosis , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Discoid/pathology , Paraffin Embedding , Pemphigoid, Bullous/diagnosis , Pemphigoid, Bullous/immunology , Pemphigoid, Bullous/pathology , Pemphigus/diagnosis , Pemphigus/immunology , Pemphigus/pathology , Retrospective Studies , Skin Diseases, Vesiculobullous/diagnosis , Skin Diseases, Vesiculobullous/immunology , Skin Diseases, Vesiculobullous/pathology
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