Biologicals in atopic disease in pregnancy: An EAACI position paper.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum.

CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response.