An Atypical Incontinentia Pigmenti Female with Persistent Mucocutaneous Hyperinflammation and Immunodeficiency Caused by a Novel Germline IKBKG Missense Mutation.

While most missense mutations of the IKBKG gene typically result in Ectodermal Dysplasia with Immunodeficiency, there have been rare reported instances of missense mutations of the IKBKG gene causing both Incontinentia Pigmenti (IP) and immunodeficiency in female patients. In this study, we described an atypical IP case in a 19-year-old girl, characterized by hyperpigmented and verrucous skin areas over the entire body. Remarkably, she experienced recurrent red papules whenever she had a feverish upper respiratory tract infection. Immunohistochemical staining unveiled a substantial accumulation of CD68+ macrophages alongside the TNF-α positive cells in the dermis tissue of new pustules, with increased apoptotic basal keratinocytes in the epidermis tissue of these lesions. Starting from the age of 8 years old, the patient suffered from severe and sustained chronic respiratory mucous membrane scar hyperplasia and occluded subglottic lumen. In addition to elevated erythrocyte sedimentation rate values, inflammatory cells were observed in the pathologic lesions of endobronchial biopsies and Bronchoalveolar Lavage Fluid (BALF) smear. Further histological analysis revealed a destructive bronchus epithelium integrity with extensive necrosis. Simultaneously, the patient experienced recurrent incomplete intestinal obstructions and lips contracture. The patient's BALF sample displayed an augmented profile of proinflammatory cytokines and chemokines, suggesting a potential link to systemic hyperinflammation, possibly underlying the pathogenic injuries affecting the subglottic, respiratory, and digestive systems. Furthermore, the patient presented with recurrent pneumonias and multiple warts accompanied by a T+BlowNKlow immunophenotype. Next generation sequencing showed that the patient carried a novel de novo germline heterozygous missense mutation in the IKBKG gene (c. 821T>C, p. L274P), located in the highly conserved CC2 domain. TA-cloning sequencing of patient's cDNA yielded 30 mutant transcripts out of 44 clones. In silico analysis indicated that the hydrogen bond present between Ala270 and Leu274 in the wild-type NEMO was disrupted by the Leu274Pro mutation. However, this mutation did not affect NEMO expression in peripheral blood mononuclear cells (PBMCs). Moreover, patient PBMCs exhibited significantly impaired TNF-α production following Lipopolysaccharide (LPS) stimulation. X-chromosome inactivation in T cells and neutrophils were not severely skewed. Reduced levels of IκBα phosphorylation and degradation in patient's PBMCs were observed. The NF-κB luciferase reporter assay conducted using IKBKG-deficient HEK293T cells revealed a significant reduction in NF-kB activity upon LPS stimulation. These findings adds to the ever-growing knowledge on female IP that might contribute to the better understanding of this challenging disorder.

Microplastics in the Bronchoalveolar Lavage Fluid of Chinese Children: Associations with Age, City Development, and Disease Features.

This study characterized the occurrence patterns of microplastics (MPs) in the bronchoalveolar lavage fluid (BALF) of children with pulmonary diseases. MPs were detected in 89.6% of BALF samples with an average of 4.31 ± 2.77 items/10 mL, supporting the hypothesis that inhalation is a significant pathway of airborne MP exposure to pediatric lungs. Inhaled MPs were predominantly composed of 10 polymer types [e.g., polypropylene (41.9%), polyethylene (19.4%), and polyester (13.6%)], with the majority being smaller than 20 µm. MP levels in BALF exhibited a negative correlation with children's age, probably owing to the preferential crawling and tumbling actions in indoor environments and underdeveloped immune systems of young children. Participants living in urban areas suffered from higher pulmonary MP exposure, likely due to higher environmental levels, compared with suburban/rural residents (P < 0.05). Although no significant differences were found between MP levels in pediatric lungs with community-acquired pneumonia (CAP) and asthma (P > 0.05), the severe CAP group displayed significantly higher MP contamination than the nonsevere group (P < 0.05), indicating that some yet undiscovered relationship(s) between inhaled MPs and pediatric pulmonary diseases may exist.