HLA-G, LILRB1 and LILRB2 Variants in Zika Virus Transmission from Mother to Child in a Population from South and Southeast of Brazil.

During the 2015-2016 epidemic, Brazil was the country with the highest rate of Zika virus (ZIKV) infection in the Americas. Twenty-nine percent of pregnant women positive for ZIKV exhibited ultrasound scans with fetus anomalies. Human leukocyte antigen-G (HLA-G) exerts immunoregulatory effects by binding to inhibitory receptors, namely LILRB1 and LILRB2, thus preventing mother-fetus rejection and vertical pathogen transmission. The binding of HLA-G to one of its receptors modulates both innate and adaptive immunity. However, in a viral infection, these molecules may behave as pathogenic mediators shifting the pregnancy environment from an anti-inflammatory profile to a pro-inflammatory phenotype. Genetic mutations might be associated with the change in phenotype. This study aimed to explore the possible role of polymorphic sites in HLA-G, LILRB1 and LILRB2 in mother-fetus ZIKV transmission. Polymorphisms were detected by direct sequencing. Differences in allele and/or genotype frequencies for each SNP analyzed among ZIKV non-transmitting and transmitting mother-child pairs, among ZIKV-transmitting and non-transmitting mothers and between ZIKV-infected and non-infected children were compared by Mid-P exact test or Yates' correction. Significant susceptibility of ZIKV vertical transmission is suggested in ZIKV-transmitting and non-transmitting mothers and ZIKV-infected and non-infected children for LILRB1_rs1061684 T/T (p = 0.03, Pc = 0.06, OR = 12.4; p = 0.008, Pc = 0.016, OR = 16.4) and LILRB1_rs16985478 A/A (p = 0.01, Pc = 0.02, OR = 19.2; p = 0.008, Pc = 0.016, OR = 16.4). HLA-G_rs1710 (p = 0.04, Pc = 0.52, OR = 4.30) was also a susceptibility factor. LILRB2_rs386056 G/A (p = 0.02, Pc = 0.08, OR = 0.07), LILRB2_rs7247451 G/G (p = 0.01, Pc = 0.04, OR = 0.04) and HLAG_rs9380142 T/T (p = 0.04, Pc = 0.52, OR = 0.14) were suggested as protective factors against vertical transmission. The current study suggests that polymorphic sites in the LILRB1 and HLA-G genes might be associated with mother-to-child ZIKV transmission while LILRB2 might be associated with protection against ZIKV transmission in the womb in a population from the south and southeast of Brazil.

Hábitos de vida de pessoas com diabetes mellitus durante a pandemia de covid-19 / Hábitos de vida de personas con diabetes mellitus durante la pandemia de covid-19 / Life habits of people with diabetes mellitus during the covid-19 pandemic

RESUMO Objetivo: caracterizar impactos do distanciamento social ocasionado pela pandemia da doença do Coronavírus na vida de pessoas com Diabetes Mellitus. Método: estudo descritivo quantitativo, realizado com 102 portadores de Diabetes Mellitus, por meio de formulário virtual, abordando questões sociodemográficas, de autocuidado e de saúde mental, no Brasil no período de maio a junho de 2020. A associação entre as variáveis foi avaliada pelo teste qui-quadrado (p<0,05). Resultados: dos 45 (44,11%) que disseram se alimentar mal, 33 (32,35%) relataram mudanças de peso (p=0,008); com relação à saúde mental, 59 (57,84%) expuseram condições regulares ou ruins; com relação às consultas, 84 indivíduos (82,75%) alegaram interrupção ou irregularidade; dos 58 (56,86%) que declararam prejuízos socioeconômicos, 37 (36,27%) apresentaram dificuldades na adesão de insumos (p<0,000). Conclusão: medidas multiprofissionais devem ser focadas nos fatores que influenciam negativamente o controle metabólico, assim como em estabelecer atendimento a distância, para minimizar a diminuição da atenção assistencial.

RESUMEN Objetivo: caracterizar los impactos del distanciamiento social provocado por la pandemia de la enfermedad por Coronavirus en la vida de las personas con Diabetes Mellitus. Método: estudio descriptivo cuantitativo, realizado con 102 pacientes con Diabetes Mellitus, a través de un formulario virtual, con el abordaje de temas sociodemográficos, de autocuidado y de salud mental, en Brasil de mayo a junio de 2020. La asociación entre variables fue evaluada por la prueba de chi-cuadrado (p<0,05). Resultados: de los 45 (44,11%) que admitieron comer mal, 33 (32,35%) reportaron cambios de peso (p=0,008); con respecto a la salud mental, 59 (57,84%) expusieron condiciones regulares o malas; En cuanto a las consultas, 84 personas (82,75%) alegaron interrupción o irregularidad; de los 58 (56,86%) que declararon pérdidas socioeconómicas, 37 (36,27%) tuvieron dificultades en la adhesión de insumos (p<0,000). Conclusión: las medidas multiprofesionales deben centrarse en los factores que influyen negativamente en el control metabólico, así como en el establecimiento de cuidados a distancia, para minimizar la disminución de la atención asistencial.

ABSTRACT Objective: to characterize the impacts of social distancing caused by the Coronavirus disease pandemic on the lives of people with Diabetes Mellitus. Method: a descriptive study with a quantitative approach, carried out in Brazil from May to June 2020 with 102 patients with Diabetes Mellitus, through a virtual form, addressing sociodemographic, self-care and mental health issues. The association between the variables was assessed using the chi-square test (p<0.05). Results: of the 45 (44.11%) individuals who stated eating poorly, 33 (32.35%) reported weight changes (p=0.008); in relation to mental health, 59 (57.84%) presented regular or bad conditions; with regard to consultations, 84 individuals (82.75%) indicated interruption or irregularity; of the 58 (56.86%) who stated socioeconomic losses, 37 (36.27%) had difficulties in adherence to inputs (p<0.000). Conclusion: multi-professional measures must be focused on the factors that exert a negative influence on metabolic control, as well as on establishing remote care, to minimize the reduction in assistance.

Association of MICA and HLA­B alleles with leprosy in two endemic populations in Brazil

Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case­control and a family­based study in two endemic populations in Brazil. MICA and HLA­B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR­SSOP­Luminex­based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi­square or Fisher's exact test together with a multivariate analysis. Family­based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002­HLA­B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA­A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA­B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA­B markers rs2596498 and rs2507992, and high LD (R2 = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA­B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele(AU).

Influence of inflammasome NLRP3, and IL1B and IL2 gene polymorphisms in periodontitis susceptibility.

The pathogenesis of periodontitis (PD) involves several molecules of the immune system that interact in a network to eliminate the periodontopathogens, yet, they contribute to periodontal tissue destruction. The different mechanisms that lead to periodontal tissue damage are not clear. Despite this, immune response genes have been related to the development of PD previously, such as those involved in inflammasomes which are multiprotein complexes and cytokines including Interleukin-1. The aim of the study was to evaluate the polymorphisms in NLRP3 inflammasome, cytokine and receptor of cytokines genes in the development of periodontitis. This case-control study was conducted in 186 patients with PD (stage II and III and grade B) and 208 controls (localized gingivitis and periodontally healthy individuals). Genotyping was performed using PCR-RFLP for the SNP rs4612666 in NLRP3 and using PCR-SSP for IL1A, IL1B, IL1R, IL1RN, IL4RA, INFG, TGFB1, TNF, IL2, IL4, IL6, and IL10. Cytokine serum levels were measured using Luminex technology. SNPStats and OpenEpi software were used to perform statistical analysis. The higher frequencies of NLRP3 T/C and IL1B -511 T/T genotypes and IL2 (+166, -330) GT haplotype were observed in patients with PD compared to controls. The SNPs in NLRP3, IL1R +1970, IL6-174, TNF -308, IL2 +166 and -330, TGFB1 +869 and +915, IL4RA +1902, IL4-1098 and -590 were associated to PD in men. In conclusion, polymorphisms in NLRP3, IL1B and IL2 genes were associated to PD susceptibility. Men carrying the NLRP3, IL1R, IL6, TNF, IL2, TGFB1, IL4RA and IL4 polymorphisms had greater susceptibility than women for developing PD.