Key elements of psoriasis immunogenetics: A review

RESUMEN: La psoriasis, que afecta de 2% a 3% de la población mundial, es una de las enfermedades cutáneas más frecuentes, Se presenta en cualquier etapa de la vida. La psoriasis tipo I o temprana comienza antes de los 40 años en tanto que la tipo II es de inicio tardío, luego de los 40 años. Tiene una fuerte base genética y la probabilidad de heredarla cuando los dos padres están afectados es hasta del 50%. Se han descrito diferentes regiones de susceptibilidad asociadas a la psoriasis, que se denominan PSORS, de las que PSORS-1 es la más frecuente. PSORS-1 está en el cromosoma 6 en el que se localiza el HLA-Cw6, que es el gen hasta ahora más relacionado con la psoriasis. La función de HLA-Cw6 en la psoriasis no está completamente entendida, pero se ha asociado con la psoriasis tipo I, la psoriasis en gotas y la presentación antigénica de una gama de antígenos entre los que se encuentran los derivados de Streptococcus pyogenes. Por otra parte, algunos polimorfismos de nucleótido simple en genes que codifican para citocinas como IL-12, IL-23, TNF-α o sus receptores, se han relacionado con la inmunopatogénesis de esta enfermedad.ABSTRACT: Psoriasis is one of the most common skin diseases, affecting 2% to 3% of the world population. It occurs at any stage of life. “Early” psoriasis or type I manifests before 40 years, and “late” psoriasis or type II, after 40 years. It has a strong genetic basis and the probability of inheriting the disease when both parents are affected is up to 50%. Different susceptibility regions associated with psoriasis, called PSORS, have been described, PSORS-1 being the most frequent one. It is in chromosome 6 and in this region HLA-Cw6 is located, which is until now the gene more associated with psoriasis. The role of HLA-Cw6 in psoriasis is not fully understood, but it has a relationship with type I psoriasis, guttate psoriasis and the presentation of an array of antigens including those derived from Streptococcus pyogenes. Furthermore, some single nucleotide polymorphisms in genes encoding cytokines such as IL-12, IL-23, TNF-α or their receptors are associated with the immunopathogenesis of the disease

Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm1 and emm12; emm12 predominated in 2022 but was surpassed by emm1 in 2023. Spread of M1UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm1, but also important representativeness of emm12 and emm89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the speA gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/emm1, ST36-ST425/emm12, ST242/emm12.37, ST39/emm4, and ST101-ST1295/emm89 isolates. IMPORTANCE: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.This research was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red-(CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU; Strategic action of the CIBER of Infectious Diseases (CIBERINFEC) 2022.S

Vitamin B1 diversity and characterization of biosynthesis genes in cassava

Vitamin B1, which consists of the vitamers thiamin and its phosphorylated derivatives, is an essential micronutrient for all living organisms because it is required as a metabolic cofactor in several enzymatic reactions. Genetic diversity of vitamin B1 biosynthesis and accumulation has not been investigated in major crop species other than rice and potato. We analyzed cassava germplasm for accumulation of B1 vitamers. Vitamin B1 content in leaves and roots of 41 cassava accessions showed significant variation between accessions. HPLC analyses of B1 vitamers revealed distinct profiles in cassava leaves and storage roots, with nearly equal relative levels of thiamin pyrophosphate and thiamin monophosphate in leaves, but mostly thiamin pyrophosphate in storage roots. Unusually, the cassava genome has two genes encoding the 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate synthase, THIC (MeTHIC1 and MeTHIC2), both of which carry a riboswitch in the 3'-UTR, as well as the adenylated thiazole synthase, THI1 (MeTHI1a and MeTHI1b). The THIC and THI1 genes are expressed at very low levels in storage roots compared with the accumulation of vitamin B1, indicating only limited biosynthesis de novo therein. In leaves, vitamin B1 content is negatively correlated with THIC and THI1 expression levels, suggesting post-transcriptional regulation of THIC by the riboswitch present in the 3'-UTR of the THIC mRNA and regulation of THI1 by promoter activity or alternative post-transcriptional mechanisms