It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on ‘HLA epitope’ frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms—thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included.

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides—e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens–Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/.

tupí linguistic groups display a wide geographical dispersion in south America, probably originated, as pointed by linguistic, from Madeira-Guaporé region (MGr) in Brazil. the present study reviewed genetic data on tupians for autosomal and uniparental (Y-chromosome and mtdnA) markers, using it to evaluate tupians geographic origin as well as the demographic dynamics of their dispersion from a genetic point of view. Comparison of genetic variability and mtdnA haplogroups d frequencies suggests a scenario where MGr is the tupí homeland. the relationship between five estimators of genetic variability (thetas-s, -Pi, -m2, -H and -k) shows that tupí groups from MGr and non-MGr experienced different patterns of demographic dynamics, with an ancient tupí expansion in MGr, followed by dispersion to other south America regions, probably associated to depopulation/founder effect events. furthermore, other recent depopulation events could also be detected in both regions. finally, the dispersion seems to be related to patrilocality, as suggested by comparison of uniparental markers genetic differentiation. this genetic model of dispersion dynamics may have an important impact in the interpretation of archeological and linguistic data, allowing to test if female associated technologies, like ceramic, are more extensively shared between dispersed populations than those which are not female-exclusive.Keywords: tupí homeland. demographic. tupí expansion. Patrilocality. Genetic markers.Resumo: Grupos linguísticos tupí exibem uma grande dispersão geográfica na América do sul, provavelmente originadas, conforme apontada pela linguistica, na região Madeira-Guaporé (MGr), Brasil. o presente estudo revisou dados geneticos de populacoes tupí para marcadores autossomicos e uniparentais (Y-cromossomo and mtdnA), delineando abordagens para avaliar origem geográfica, bem como a dinâmica demográfica de sua dispersão, de um ponto de vista genético. Comparação da variabilidade genetica e das frequencias do haplogrupo d do mtdnA sugere um cenário onde MGr é o local de origem tupí. A relação entre cinco estimadores de variabilidade genetica thetas-s, -Pi, -m2, -H e -k) mostram que grupos tupí da MGr não MGr experienciaram diferentes padrões de dinâmica demográfica, com uma antiga expansão tupí em MGr, seguida de dispersão para outras regiões da América do sul, provavelmente associada a eventos de depopulação/efeito fundador. Além disso, outros eventos recentes de depopulação também puderam ser detectados em ambas as regiões. finalmente, a dispersão parece estar relacionada com práticas de patrilocalidade, como sugerido pela comparação de marcadores uniparentais. Este modelo genético de dinâmica de dispersão tupí pode ter um impacto importante na interpretação dos dados arqueológicos e linguísticos, permitindo testar se tecnologias associadas ao sexo feminino, como a cerâmica, são mais amplamente compartilhadas entre populações dispersas do que tecnologias não exclusivas do sexo feminino.

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development.