Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. MethodsWe did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. FindingsIn the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.
We investigated the role of tobacco and alcohol consumption on the occurrence of head and neck squamous cell carcinomas (HNSCC), and the joint effects of these factors with oral human papillomavirus (HPV) infection in the French West Indies, in the Caribbean. We conducted a population‐based case‐control study (145 cases and 405 controls). We used logistic regression models to estimate adjusted odds ratios (OR) and their 95% confidence intervals (CI). Two‐way interactions were assessed on both multiplicative and additive scales. Current smoking (OR = 11.6, 95% CI = 6.7‐20.1), drinking more than five glasses of alcohol per day (OR = 2.7, 95% CI = 1.2‐4.7), and oral infection with High‐risk HPV (OR = 2.4, 95% CI = 1.1‐5.0) were significantly associated with HNSCC. The combined exposure to tobacco and alcohol produced a significant synergistic effect on the incidence of HNSCC. Oral infection with High‐risk HPV increased the risk of HNSCC in never smokers and nondrinkers. The effects of tobacco, alcohol, and of the combined exposure of tobacco and alcohol were substantially lower in HPV‐positive than in HPV‐negative HNSCC. This is the first case‐control study to investigate the role of tobacco smoking, alcohol drinking and oral HPV infection in an Afro‐Caribbean population. Although each of these risk factors has a significant effect, our findings indicate that tobacco and alcohol play a less important role in Hr‐HPV‐positive HNSCC. Further investigations are warranted notably on the interaction of these three risk factors by cancer site.
This study revealed a high prevalence of oral HPV infection in this middle-aged Afro-Caribbean population, and a specific distribution of HPV genotypes. These findings may provide insight into HNSCC etiology specific to the FWI.
Sequencing and other biological data are now more frequently available and at a lower price. Mutual tools and strategies are needed to analyze the huge amount of heterogeneous data generated by several research teams and devices. Bioinformatics represents a growing field in the scientific community globally. This multidisciplinary field provides a great amount of tools and methods that can be used to conduct scientific studies in a more strategic way. Coordinated actions and collaborations are needed to find more innovative and accurate methods for a better understanding of real life data. A wide variety of organizations are contributing to KaruBioNet in Guadeloupe (French West Indies), a Caribbean archipelago. The purpose of this group is to foster collaboration and mutual aid among people from different disciplines using a ‘one health’ approach, for a better comprehension and surveillance of humans, plants, or animals’ health and diseases. The KaruBioNet network particularly aims to help researchers in their studies related to ‘omics’ data, but also more general aspects concerning biological data analysis. This transdisciplinary network is a platform for discussion, sharing, training and support between scientists interested in bioinformatics and related fields. Starting from a little archipelago in the Caribbean, we envision to facilitate exchange between other Caribbean partners in the future, knowing that the Caribbean is a region with non-negligible biodiversity which should be preserved and protected. Joining forces with other Caribbean countries or territories would strengthen scientific collaborative impact in the region. Information related to this network can be found at: http://www.pasteur-guadeloupe.fr/karubionet.html. Furthermore, a dedicated “Galaxy KaruBioNet” platform is available at: http://calamar.univ-ag.fr/c3i/galaxy_karubionet.html. Supplementary information Supplementary data are available at Bioinformatics Advances online.
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