Clinical and genetic characterization of Netherton syndrome due to SPINK5 founder variant in Latvian population.

OBJECTIVE: Netherton syndrome (NS) (OMIM:256500) is a very rare autosomal recessive multisystem disorder mostly affecting ectodermal derivatives (skin and hair) and immune system. It is caused by biallelic loss-of-function variants in the SPINK5 gene, encoding the protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI). MATERIAL, METHODS AND RESULTS: Here, we describe NS clinical and genetic features of homogenous patient group: 9 individuals from 7 families with similar ethnic background and who have the same SPINK5 variant (NM_006846.4: c.1048C > T, p.(Arg350*)) in homozygous or compound heterozygous states, suggesting that it is a common founder variant in Latvian population. Indeed, we were able to show that the variant is common in general Latvian population, and it shares the same haplotype among the NS individual. It is estimated that the variant arose >1000 years ago. Clinically, all nine patients exhibited typical NS skin changes (scaly erythroderma, ichthyosis linearis circumflexa, itchy skin), except for one patient who has a different skin manifestation-epidermodysplasia. Additionally, we show that developmental delay, previously underrecognized in NS, is a common feature among these patients. CONCLUSIONS: This study shows that the phenotype of NS individuals with the same genotype is highly homogeneous.

Long-Term Immunological Memory of SARS-CoV-2 Is Present in Patients with Primary Antibody Deficiencies for up to a Year after Vaccination.

Some studies have found increased coronavirus disease-19 (COVID-19)-related morbidity and mortality in patients with primary antibody deficiencies. Immunization against COVID-19 may, therefore, be particularly important in these patients. However, the durability of the immune response remains unclear in such patients. In this study, we evaluated the cellular and humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in a cross-sectional study of 32 patients with primary antibody deficiency (n = 17 with common variable immunodeficiency (CVID) and n = 15 with selective IgA deficiency) and 15 healthy controls. Serological and cellular responses were determined using enzyme-linked immunosorbent assay and interferon-gamma release assays. The subsets of B and T lymphocytes were measured using flow cytometry. Of the 32 patients, 28 had completed the vaccination regimen with a median time after vaccination of 173 days (IQR = 142): 27 patients showed a positive spike-peptide-specific antibody response, and 26 patients showed a positive spike-peptide-specific T-cell response. The median level of antibody response in CVID patients (5.47 ratio (IQR = 4.08)) was lower compared to healthy controls (9.43 ratio (IQR = 2.13)). No difference in anti-spike T-cell response was found between the groups. The results of this study indicate that markers of the sustained SARS-CoV-2 spike-specific immune response are detectable several months after vaccination in patients with primary antibody deficiencies comparable to controls.

Mepolizumab: Therapeutic strategy for a pediatric patient with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis. It is a multisystem disorder and can affect every organ system. EGPA is a rare disease, with an estimated prevalence of 1/70,000-100,000 in Europe. As its onset usually occurs in adulthood, data from pediatric patients are limited. We present here a very rare practical EGPA clinical case involving a pediatric patient. Presently, data on mepolizumab usage in pediatric patients are limited, with only a few case reports published.