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Background: Viral infection outcomes vary widely between individuals, ranging from mild symptoms to severe organ failure and death, and it is clear that host genetic factors play a role in this variability. Type I interferon (IFN) is a critical anti-viral cytokine, and we have previously noted differences in type I IFN levels between world populations., Methods: In this study, we investigate the interrelationship between regional European genetic ancestry, type I IFN levels and severe viral infection outcomes., Results: In cohorts of European ancestry lupus patients living in Europe, we noted higher IFN in the Northwestern populations as compared to Southeastern populations. In an independent cohort of European ancestry lupus patients from the USA with varying proportional regional European genetic admixture, we observed the same Northwest vs. Southeast European ancestry IFN gradient. We developed a model to predict type I IFN level based on regional European ancestry (Area under the curve (AUC) = 0.73, P = 6.1e-6). Examining large databases containing serious viral outcomes data, we found that lower predicted IFN in the corresponding European country was significantly correlated with increased viral infection fatality rate, including Coronavirus Disease 2019 (COVID-19), viral hepatitis and HIV [correlation coefficients: -0.79 (P = 4e-2), -0.94 (P = 6e-3) and -0.96 (P = 8e-2), respectively]., Conclusions: This association between predicted type I IFN level and viral outcome severity suggests a potential causal relationship, as greater intrinsic type I IFN is beneficial in host defense against viruses. Genetic testing could provide insight into individual and population level risk of fatality due to viruses prior to infection, across a wide range of viral pathogens., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The aim was to evaluate the cross-cultural validity of the Lupus Impact Tracker (LIT) in five European countries and to assess its acceptability and feasibility from the patient and physician perspectives., Methods: A prospective, observational, cross-sectional and multicentre validation study was conducted in clinical settings. Before the visit, patients completed LIT, Short Form 36 (SF-36) and care satisfaction questionnaires. During the visit, physicians assessed disease activity [Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI], organ damage [SLICC/ACR damage index (SDI)] and flare occurrence. Cross-cultural validity was assessed using the Differential Item Functioning method., Results: Five hundred and sixty-nine SLE patients were included by 25 specialists; 91.7% were outpatients and 89.9% female, with mean age 43.5 (13.0) years. Disease profile was as follows: 18.3% experienced flares; mean SELENA-SLEDAI score 3.4 (4.5); mean SDI score 0.8 (1.4); and SF-36 mean physical and mental component summary scores: physical component summary 42.8 (10.8) and mental component summary 43.0 (12.3). Mean LIT score was 34.2 (22.3) (median: 32.5), indicating that lupus moderately impacted patients' daily life. A cultural Differential Item Functioning of negligible magnitude was detected across countries (pseudo- R 2 difference of 0.01-0.04). Differences were observed between LIT scores and Physician Global Assessment, SELENA-SLEDAI, SDI scores = 0 (P < 0.035) and absence of flares (P = 0.004). The LIT showed a strong association with SF-36 physical and social role functioning, vitality, bodily pain and mental health (P < 0.001). The LIT was well accepted by patients and physicians. It was reliable, with Cronbach α coefficients ranging from 0.89 to 0.92 among countries., Conclusion: The LIT is validated in the five participating European countries. The results show its reliability and cultural invariability across countries. They suggest that LIT can be used in routine clinical practice to evaluate and follow patient-reported outcomes in order to improve patient-physician interaction., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: To compare the clinical results after treatment with B-cell depleting therapy in patients with membranous (WHO Class V) vs proliferative (WHO Class III or IV) lupus nephritis (LN)., Methods: Data were compiled from two European centres on all patients with LN who were treated with i.v. rituximab (RTX) in a combination protocol with i.v. cyclophosphamide and steroids. Laboratory and serological evaluations were performed at 3, 6 and 12 months of follow-up. No immunosuppressive drugs were given before B-cell repopulation., Results: Forty-three patients, 28 with proliferate and 15 with membranous LN by renal biopsy, were evaluated. Six months after treatment with RTX, both the membranous and the proliferative LN patients had a significant reduction in proteinuria and an increase in serum albumin. The main improvements were observed during the first 6 months and only minor non-significant changes in albumin and proteinuria were observed thereafter. As expected, the patients with membranous nephritis had lower anti-dsDNA titres and higher complement C3 levels at baseline, but in both groups a significant reduction in anti-dsDNA titre and improvements in complement C3 levels were seen during the first 6 months after treatment; the kinetics of improvement were similar in both groups., Conclusion: The clinical course following B-cell depleting therapy is strikingly similar between patients with membranous and those with proliferative LN. These observational data suggest that, if controlled studies confirm the efficacy of B-cell depleting therapy in proliferative nephritis, clinicians may reasonably consider such therapy in membranous LN.