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CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαβ+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αβ T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei., (© 2024 Guérin et al.)

Background: There are emerging eosinophil-related considerations concerning viral infections. The role of eosinophils has poorly been evaluated during Hantavirus infection., Methods: The aim of this study was to determine the prevalence of eosinophilia (defined as an eosinophil count above 500 cells/mm 3 ) during haemorrhagic fever with renal syndrome (HFRS) in a large cohort of patients, and to identify factors associated with eosinophilia., Results: Among 387 patients hospitalized for HFRS, 98 (25.3%) had eosinophilia. By univariate analysis, eosinophilia was significantly associated with more severe thrombocytopenia, high C-reactive protein level, white blood cell count and neutrophil count and lower nephrotoxic drug intake. As there was a collinearity between white blood cell count and C-reactive protein level, only C-reactive protein level with platelet count and nephrotoxic drug intake were entered in the multivariable analysis. Elevated C-reactive protein concentrations remained independently associated with eosinophilia., Conclusion: Eosinophilia during HFRS affects one quarter of patients, and supports the role of eosinophils in antiviral immunity against hantavirus infection.

Background: Amoxicillin crystalluria (AC), potentially responsible for acute kidney injury (AKI), is reported more and more frequently in patients treated with high doses of intravenous amoxicillin (HDIVA). The main objective of this study was to evaluate AC incidence in these patients. The secondary objectives were to identify factors associated with AC and to evaluate its impact on the risk of AKI., Methods: This multicentre, observational, cohort study was conducted between Mar 18, 2014 and Aug 16, 2019 in Dijon, Nancy, and Reims University Hospitals as well as Châlon-sur-Saône, Charleville-Mézières, and Troyes general hospitals in France. Adult patients (≥18 years) treated with HDIVA and having been tested for AC at least once during treatment were included. Clinical, biological, and therapeutic characteristics of the patients were collected. A univariable mixed logistic regression model assessed the factors associated with AC. A multivariable Cox model with AC as a time-dependent variable assessed the prognostic factors for AKI. ClinicalTrials.gov number: NCT02853292., Findings: Of the 112 included patients, 27 (24.1%, 95% CI [16.2-32.0]) developed at least one episode of AC within a mean of 5.1 days. The factors associated with its occurrence were the concomitant use of angiotensin converting enzyme (ACE) inhibitors (OR=4.6, 95% CI [2.2-9.3], p<0.0001) and the decrease of urinary pH (OR=2.1 for one pH point decrease, 95% CI [1.2-3.7], p=0.009). 20 patients (17.9%) presented with AKI, within a mean time of 10.9 days. The main factor associated with the occurrence of AKI was the occurrence of AC (aHR=7.4, 95% CI [2.5-22.2], p=0.0003)., Interpretation: AC occurred in a quarter of patients treated with HDIVA and was highly prognostic of AKI., Funding: None., Competing Interests: We declare no competing interests., (© 2022 The Author(s).)

We conducted a multicenter, retrospective cohort study of hospitalized patients with serologically proven nephropathia epidemica (NE) living in Ardennes Department, France, during 2000-2014 to develop a bioclinical test predictive of severe disease. Among 205 patients, 45 (22.0%) had severe NE. We found the following factors predictive of severe NE: nephrotoxic drug exposure (p = 0.005, point value 10); visual disorders (p = 0.02, point value 8); microscopic or macroscopic hematuria (p = 0.04, point value 7); leukocyte count >10 × 10 9 cells/L (p = 0.01, point value 9); and thrombocytopenia <90 × 10 9 /L (p = 0.003, point value 11). When point values for each factor were summed, we found a score of <10 identified low-risk patients (3.3% had severe disease), and a score >20 identified high-risk patients (45.3% had severe disease). If validated in future studies, this test could be used to stratify patients by severity in research studies and in clinical practice.

Objectives: To validate the Fautrel classification criteria for adult-onset Still's disease (AOSD) and to compare the discriminative performance to that of the Yamaguchi criteria., Methods: We retrospectively reviewed the medical charts of 426 patients who had serum ferritin level and percentage glycosylated ferritin assayed at the biochemistry laboratory of Bichat Hospital. Medical data were extracted by use of a standardized form. All clinical, biological, and imaging features were collected, as well, evidence favoring an alternative diagnosis, specifically symptoms suggestive of other immune-mediated inflammatory diseases (IMID) or active infections. Patients were classified as AOSD patients or controls according to a predefined procedure, including consultation with a multidisciplinary expert group. Algorithms corresponding to the Fautrel and Yamaguchi classification criteria were applied for each patient., Results: In all, 54 AOSD and 278 control patients were included. For the Fautrel criteria, the sensitivity was 87.0%, specificity 97.8%, and positive and negative predictive values 88.7% and 97.5%, respectively. For the standard Yamaguchi set-without strict application of exclusion criteria-the sensitivity was 96.3%, specificity 98.9%, and positive and negative predictive values 94.5% and 99.3%, respectively. If we applied a stricter definition of exclusion criteria, the sensitivity of the Yamaguchi set decreased to 31.5%. As wall, 37 AOSD diagnoses were missed., Conclusion: This study validates the Fautrel classification criteria with a cohort independent of that used for the original publication. This criteria set demonstrates good sensitivity and specificity, overcomes exclusion criteria, and includes glycosylated ferritin level. It also confirms the high discriminative power of the Yamaguchi criteria, albeit substantially affected by how exclusion criteria are interpreted., (Copyright © 2018 Elsevier Inc. All rights reserved.)