Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

Journal of Clinical Immunology - Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable...     

Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study

Background:

Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma.

Methods:

We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study.

Results:

Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women.

Conclusions:

Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.     

Risk of malignant lymphoma following viral hepatitis infection

We investigated lymphoma risk following hepatitis infection in a case-control study of 274 incident lymphoma cases, defined according to the WHO classification, and 336 population controls in Sardinia, Italy. Part of our study population (198 cases and 219 controls) was included in the EPILYMPH study of Hepatitis C virus (HCV) infection in relation to non-Hodgklin's lymphoma risk. Based on questionnaire information on whether and at what age a diagnosis of hepatitis was posed by a physician, systematic anti-HCV antibodies testing in cases and controls by enzyme-linked immunoassay, and HCV-RNA assessment by PCR analyses in positive samples, we investigated more in detail whether hepatitis non-C is also associated with lymphoma risk, and whether risk varies by clinical form of hepatitis (acute or chronic infection). After adjusting by age, gender, education, and area of birth whether from the study area or elsewhere in Italy, a previous generic diagnosis of hepatitis was associated with a significantly elevated lymphoma risk [odds ratio (OR) = 1.8; 95% CI 1.1, 2.8], which was equally increased for hepatitis B (OR = 1.8; 95% CI 0.9, 3.5), for HCV positive subjects overall (OR = 2.0; 95% CI 0.8, 4.8), and for hepatitis non-B non-C (OR = 1.6; 95% CI 0.7, 3.9). Once concurrent infection from other hepatitis viruses was excluded, acute or chronic hepatitis C was the only one showing a consistent risk increase in all lymphoma subtypes, but follicular lymphoma. Some indications of an excess risk of lymphoma were observed also for acute, but not chronic forms of hepatitis B and hepatitis non-B, non C. Self-limited hepatitis C did not show an association. No significant heterogeneity in the risk of major lymphoma subtype was observed. Our results confirm a role of either acute or chronic active HCV infection in lymphomagenesis. Further studies are warranted to test the hypothesis that acute infection from other hepatitis viruses might also increase lymphoma risk.     

Test–retest reliability of an infectious disease questionnaire and evaluation of self-assessed vulnerability to infections

Introduction/objectives

Large scale population-based studies focusing on infectious diseases are scarce. This may be explained by methodological obstacles concerning ascertainment of data on infectious diseases requiring, e.g. collection of data on relatively short-termed symptoms and/or collection of biosamples for pathogen identification during a narrow time window. In the German National Cohort (GNC), a novel self-administered questionnaire will be used in addition to biosampling to collect data on selected infectious diseases and symptoms. The aim of this study was to evaluate in Pretest 2 of the GNC newly added items on self-assessed vulnerability to several infectious diseases and to assess test–retest reliability of the questionnaire.

Methods

The study was conducted in two study centres (Hamburg and Hanover) during Pretest 2 of the GNC. A self-administered paper questionnaire was applied. In Hamburg, participants were asked to fill in the questionnaire during their regular visit at the study centre. For test–retest reliability, participants in Hanover filled in the same questionnaire at home twice. To evaluate agreement, item-related percentage agreement and kappa (κ) were calculated. In addition, we computed Bennet’s S and Krippendorf’s alpha (α). Items on self-assessed vulnerability to infections were evaluated by comparing them with the corresponding self-reported frequency of infections. An explanatory factor analysis was applied to construct the scores of self-reported infection frequency and self-assessed vulnerability to infections.

Results

The evaluation of the internal consistency of the five-item instrument of self-assessed vulnerability to infections resulted in a Cronbach’s α of 0.78. The factor analysis yielded evidence of one factor. The factor was divided into three groups (lowest quintile classified as “less prone to infections” compared to peers; second, middle and fourth quintiles classified as “similarly prone to infections” and highest quintile classified as “more prone to infections”). Participants classified as “less prone to infections” reported fewer infections than participants classified as “more prone to infections”. Spearman’s correlation of the two scores (self-reported infection frequency and self-assessed vulnerability to infection) was 0.50 (p?n?=?75). The weighted κ ranged between 0.65 and 0.87 for the items on infectious disease frequency in the last 12 months, for items on symptom frequency in the past 12 months between 0.77 and 0.90, and for items on vulnerability compared to peers between 0.68 and 0.76.

Conclusion

A five-item instrument on self-assessed vulnerability to infections seems to be promising, but requires further evaluation. Overall, the questionnaire on self-reported infectious diseases used in Pretest 2 of the GNC is a moderately reliable instrument and, thus, can be applied in future studies on infectious diseases.     

Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH

BACKGROUND & AIMS: Increasing evidence points toward a role of hepatitis C virus (HCV) infection in the etiology of malignant lymphomas. However, previous epidemiologic studies were limited in size to establish an association between HCV infection and specific lymphoma subtypes. We performed a large, multicenter, case-control study to address this question. METHODS: The study comprised 5 European countries and included newly diagnosed cases of any lymphoid malignancy recruited between 1998 and 2004. Controls were matched to cases by 5-year age group, sex, and study center. In-person interviews were conducted to collect data on demographic, medical, and family history as well as environmental exposures. Serum samples of 1807 cases and 1788 controls (excluding human immunodeficiency virus-positive and organ-transplantation subjects) were screened for HCV infection using an enzyme immunoassay. Positive as well as randomly selected negative samples were subjected to HCV RNA detection and HCV genotyping. RESULTS: HCV infection was detected in 53 (2.9%) lymphoma cases and in 41 (2.3%) control subjects (odds ratio [OR], 1.42; 95% confidence interval [CI]: 0.93-2.15). Restricted to individuals who tested positive for HCV-RNA (indicating persistent infection and active viral replication), the OR was 1.82 (95% CI: 1.13-2.91). In subtype-specific analyses, HCV prevalence was associated with diffuse large B-cell lymphoma (OR, 2.19; 95% CI: 1.23-3.91) but not with chronic lymphocytic leukemia or follicular, Hodgkin's, or T-cell lymphoma. The sample size was not sufficient to derive any conclusions for rare lymphoma entities such as splenic marginal zone lymphoma. CONCLUSIONS: These results support a model that chronic HCV replication contributes to lymphomagenesis and establish a specific role of HCV infection in the pathogenesis of diffuse large B-cell lymphoma.     

Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency

The gene PIK3CD codes for the catalytic subunit of phosphoinositide 3‐kinase δ (PI3K δ ), and is expressed solely in leucocytes. Activating mutations of PIK3CD have been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain‐of‐function mutations in PIK3CD and a loss of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the cohort. Our patients with activated PI3Kδ syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells. PIK3CD gain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell/hypogammaglobulinaemia phenotype.     

Association between personal use of hair dyes and lymphoid neoplasms in Europe

Hair dyes have been evaluated as possibly being mutagenic and carcinogenic in animals. Studies of the association between human cancer risk and use of hair dyes have yielded inconsistent results. The authors evaluated the risk of lymphoid malignancies associated with personal use of hair dyes. The analysis included 2,302 incident cases of lymphoid neoplasms and 2,417 hospital- or population-based controls from the Czech Republic, France, Germany, Ireland, Italy, and Spain (1998-2003). Use of hair dyes was reported by 74% of women and 7% of men. Lymphoma risk among dye users was significantly increased by 19% in comparison with never use (odds ratio (OR) = 1.19, 95% confidence interval (CI): 1.00, 1.41) and by 26% among persons who used hair dyes 12 or more times per year (OR = 1.26, 95% CI: 1.00, 1.60; p for linear trend = 0.414). Lymphoma risk was significantly higher among persons who had started coloring their hair before 1980 (OR = 1.37, 95% CI: 1.09, 1.72) and persons who had used hair dyes only before 1980 (OR = 1.62, 95% CI: 1.10, 2.40). Personal use of hair dyes is associated with a moderate increase in lymphoma risk, particularly among women and persons who used dyes before 1980. Specific compounds associated with this risk remain to be elucidated.