Antibodies, Monoclonal, Humanized , Pemphigoid, Bullous , Psoriasis , Humans , Psoriasis/drug therapy , Psoriasis/complications , Antibodies, Monoclonal, Humanized/therapeutic use , Pemphigoid, Bullous/drug therapy , Pemphigoid, Bullous/complications , Male , Treatment Outcome , Female , Dermatologic Agents/therapeutic use
Autoantibodies , Autoantigens , B-Lymphocytes , Collagen Type XVII , Immunoglobulin A , Immunoglobulin G , Non-Fibrillar Collagens , Pemphigoid, Benign Mucous Membrane , Humans , Autoantibodies/immunology , Immunoglobulin A/immunology , Pemphigoid, Benign Mucous Membrane/immunology , Pemphigoid, Benign Mucous Membrane/diagnosis , Non-Fibrillar Collagens/immunology , Immunoglobulin G/immunology , Autoantigens/immunology , B-Lymphocytes/immunology , Female , Male , Aged
IgA pemphigus is an autoimmune bullous disease caused by anti-keratinocyte cell surface IgA autoantibodies. Mucous membrane involvement is rare in IgA pemphigus. We report a case of IgA pemphigus with oral mucosal lesions, in which acantholysis was pathologically confirmed. A 31-year-old woman presented with skin erythema with small pustules and oral mucosal erosions. Histopathological examination of the erosions on her oral mucosa and papules on her back revealed acantholysis and intraepidermal infiltration of neutrophils. Direct immunofluorescence tests showed intercellular deposition of IgA, but not IgG, mainly in the lower, but not entire, layer of the epidermis. C3 was linearly present in the basement membrane zone (BMZ), but not in the intercellular space. Enzyme-linked immunosorbent assay revealed that both anti-desmoglein (Dsg) 3 IgA and IgG were positive. Neither IgA nor IgG against desmocollin 1-3 were detected. This case was clinically and histologically compatible with IgA pemphigus, but immunologically anti-BMZ autoimmunity was additionally observed. IgA pemphigus is classified into two major types: subcorneal pustular dermatosis type and intraepidermal neutrophilic dermatosis type. This case was not typical in terms of rarely observed oral lesions and predominant deposition of IgA in the lower layer of the epidermis. Instead, this case could be considered a rare subtype of IgA pemphigus, IgA-pemphigus vulgaris. Oral lesions in IgA pemphigus may be clinical clue of having anti-Dsg3 IgA that cannot be routinely examined.
Pathogenic variants in ABCA12 are important causative genetic defects for autosomal recessive congenital ichthyoses (ARCI), which include congenital ichthyosiform erythroderma (CIE), harlequin ichthyosis, and lamellar ichthyosis. In addition, pathogenic variants in ABCA12 are known to cause a localized nevoid form of CIE due to recessive mosaicism. We previously reported siblings who carried an ABCA12 variant but did not show a "congenital" phenotype. They were considered to have pityriasis rubra pilaris (PRP). Here, we present a further patient with ABCA12 variants whose phenotype was not congenital ichthyosis, in an independent family. Notably, these three patients had geographic unaffected areas. Such areas are not usually found in patients with ARCI who have ABCA12 variants, suggesting mild phenotypes for these patients. Interestingly, the histological features of the ichthyotic lesions in these patients resembled those of PRP. All three patients had homozygous pathogenic missense variants in ABCA12. Our findings expand the phenotypic spectrum of patients with ABCA12 variants.
Ichthyosiform Erythroderma, Congenital , Ichthyosis, Lamellar , Ichthyosis , Pityriasis Rubra Pilaris , Humans , Pityriasis Rubra Pilaris/genetics , Ichthyosis, Lamellar/genetics , Ichthyosiform Erythroderma, Congenital/genetics , Ichthyosiform Erythroderma, Congenital/pathology , Phenotype , Mutation , ATP-Binding Cassette Transporters/genetics
Dermatitis Herpetiformis , Dipeptidyl-Peptidase IV Inhibitors , Pemphigus , Humans , Pemphigus/diagnosis , Pemphigus/drug therapy , Desmocollins , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Autoantibodies , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases , Dermatitis Herpetiformis/diagnosis , Dermatitis Herpetiformis/drug therapy
Linear IgA Bullous Dermatosis , Psoriasis , Skin Abnormalities , Skin Diseases , Humans , Linear IgA Bullous Dermatosis/chemically induced , Linear IgA Bullous Dermatosis/diagnosis , Pemetrexed/adverse effects , Nivolumab/adverse effects , Blister/chemically induced , Psoriasis/drug therapy , Immunoglobulin A
Autoantibodies , Desmoglein 3 , Lymphoma, Follicular , Paraneoplastic Syndromes , Pemphigus , Humans , Pemphigus/immunology , Pemphigus/diagnosis , Pemphigus/pathology , Pemphigus/complications , Lymphoma, Follicular/complications , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/immunology , Lymphoma, Follicular/pathology , Lymphoma, Follicular/drug therapy , Paraneoplastic Syndromes/immunology , Paraneoplastic Syndromes/diagnosis , Paraneoplastic Syndromes/etiology , Paraneoplastic Syndromes/pathology , Desmoglein 3/immunology , Autoantibodies/blood , Autoantibodies/immunology , Male , Skin/pathology , Skin/immunology , Female , Middle Aged , Aged
Introduction: Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype. Methods: To better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome. Results: Through this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e-/- and Clec4d-/- mice as well as in neutrophil-specific Clec4n-/- mice. Deficiency in these genes did not reduce disease in the EBA model. Discussion: Collectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.
Epidermolysis Bullosa Acquisita , Humans , Animals , Mice , Neutrophils , Autoantibodies , Skin , Blister