ABSTRACT
BACKGROUND: Atopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood. OBJECTIVE: We identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features. METHODS: We clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients. RESULTS: Targeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD. CONCLUSION: These findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.
Subject(s)
Dermatitis, Atopic/genetics , Facial Dermatoses/genetics , Genetic Predisposition to Disease , Immunity, Innate/genetics , Adult , Aged , Dermatitis, Atopic/immunology , Facial Dermatoses/immunology , Female , Genotype , Humans , Japan , Male , Membrane Glycoproteins/genetics , Middle Aged , Neck , Polymorphism, Single Nucleotide , Receptors, Interleukin-1/genetics , Toll-Like Receptor 1/genetics , Young AdultSubject(s)
Cholangitis, Sclerosing/surgery , Graft vs Host Disease/therapy , Liver Transplantation/adverse effects , Pyrazoles/therapeutic use , Adrenal Cortex Hormones/metabolism , Adult , Brain Diseases/complications , Colitis/virology , Cytomegalovirus Infections/complications , Enzyme Inhibitors/therapeutic use , Female , Graft Survival , Herpesvirus 6, Human , Humans , Male , Middle Aged , Nitriles , Postoperative Complications , Pyrimidines , Remission Induction , Roseolovirus Infections/complications , Treatment OutcomeABSTRACT
Thymoma-associated multi-organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft-versus-host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD-like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD-like erythroderma.
