Emerging data indicate that SARS-CoV-2-specific CD8
T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals
. However, very little information is currently ...available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8
T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8
T cell epitopes. We also perform a high-resolution ex vivo analysis of pre-existing and induced SARS-CoV-2-specific CD8
T cells, applying peptide-loaded major histocompatibility complex class I (pMHCI) tetramer technology. We observe rapid induction, prolonged contraction and emergence of heterogeneous and functionally competent cross-reactive and induced memory CD8
T cell responses in cross-sectionally analyzed individuals with mild disease following SARS-CoV-2 infection and three individuals longitudinally assessed for their T cells pre- and post-SARS-CoV-2 infection. SARS-CoV-2-specific memory CD8
T cells exhibited functional characteristics comparable to influenza-specific CD8
T cells and were detectable in SARS-CoV-2 convalescent individuals who were seronegative for anti-SARS-CoV-2 antibodies targeting spike (S) and nucleoprotein (N). These results define cross-reactive and induced SARS-CoV-2-specific CD8
T cell responses as potentially important determinants of immune protection in mild SARS-CoV-2 infection.
Newly established blood DNA methylation markers that are strongly associated with smoking might open new avenues for lung cancer (LC) screening. We aimed to assess the performance of the top hits ...from previous epigenome-wide association studies in prediction of LC incidence. In a prospective nested case-control study, DNA methylation at
(cg05575921),
(cg06126421), and
(cg03636183) were measured by pyrosequencing in baseline whole blood samples of 143 incident LC cases identified during 11 years of follow-up and 457 age- and sex-matched controls without diagnosis of LC until the end of follow-up. The individual and joint associations of the 3 markers with LC risk were estimated by logistic regression, adjusted for potential confounders including smoking status and cigarette pack-years. The predictive performance was evaluated for both the individual markers and their combinations derived from multiple algorithms.
Pronounced demethylation of all 3 markers was observed at baseline among cases compared to controls. Risk of developing LC increased with decreasing DNA methylation levels, with adjusted ORs (95% CI) of 15.86 (4.18-60.17), 8.12 (2.69-4.48), and 10.55 (3.44-32.31), respectively, for participants in the lowest quartile of
,
, and
compared to participants in the highest 2 quartiles of each site among controls. The individual 3 markers exhibited similar accuracy in predicting LC incidence, with AUCs ranging from 0.79 to 0.81. Combination of the 3 markers did not improve the predictive performance (AUC = 0.80). The individual markers or their combination outperformed self-reported smoking exposure particularly in light smokers. No variation in risk prediction was identified with respect to age, follow-up time, and histological subtypes.
,
, and
methylation in blood DNA are predictive for LC development, which might be useful for identification of risk groups for further specific screening, such as CT examination.
Respiratory tract infections (RTIs) are a major morbidity factor contributing largely to health care costs and individual quality of life. The aim of the study was to test whether obesity (BMI ≥ ...30 kg/m
) is one of the risk factors underlying frequent RTIs in the German adult population.
We recruited 1455 individuals between 18 to 70 years from a cross-sectional survey on airway infections in Germany and invited them to self-report in diaries incident RTIs experienced during three consecutive winter/spring seasons. RTIs reported in these 18 months and summary measures adding-up individual RTIs were the outcomes of interest.
Compared to individuals with normal weight, obese individuals reported a consistently higher frequency of upper and lower RTIs and predominantly fell in the upper 10% group of a diary sumscore adding-up 10 different RTI symptoms over time. Obesity was associated both with lower RTIs (
OR = 2.02, 95%CI = 1.36-3.00) and upper RTIs (
OR = 1.55, 95%CI = 1.22-1.96). Adjusting for demographic and lifestyle variables did only marginally affect ORs. Stratified analyses suggested a stronger association for women and effect modifications by sports activity and dietary habits.
We confirm the association of obesity with infection burden and present evidence for putative interaction with sports activity and dietary patterns.
Purpose
Common variable immune deficiency (CVID) confers an increased risk of lymphoid neoplasms, but reports describing the precise WHO specification of the lymphoma subtypes and their immunological ...environment are lacking. We therefore classified lymphomas—occurring in a cohort of 21 adult CVID patients during a 17-year period at our center—according to the 2016 WHO classification and characterized the local and systemic immunological context
Results
The median time between the onset of CVID and lymphoma was 14 years. Patients showed a high prevalence of preceding immune dysregulation: lymphadenopathy (
n
= 13, 62%), splenomegaly (
n
= 18, 86%), autoimmune cytopenia (
n
= 14, 67%), and gastrointestinal involvement (
n
= 15, 71%). The entities comprised extranodal marginal zone lymphoma (
n
= 6), diffuse large B cell lymphoma (
n
= 7), plasmablastic lymphoma (
n
= 1), classic Hodgkin lymphoma (
n
= 4, including three cases with germline
CTLA
4 mutations), T cell large granular lymphocytic leukemia (
n
= 2), and peripheral T cell lymphoma, not otherwise specified (
n
= 1), but no follicular lymphoma. An Epstein-Barr virus association was documented in eight of 16 investigated lymphomas. High expression of PDL1 by tumor cells in five and of PDL1 and PD1 by tumor-infiltrating macrophages and T cells in 12 of 12 investigated lymphomas suggested a tolerogenic immunological tumor environment.
Conclusion
In summary, a diverse combination of specific factors like genetic background, chronic immune activation, viral trigger, and impaired immune surveillance contributes to the observed spectrum of lymphomas in CVID. In the future, targeted therapies, e.g., PD1/PDL1 inhibitors in CVID associated lymphomas with a tolerogenic environment may improve therapy outcome.
Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We ...examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.
Background
Patients with cancer are considered a high‐risk group for viral pneumonia, with an increased probability of fatal outcome. Here, we investigated the clinical characteristics and outcome of ...patients with solid and hematological cancers and concomitant Covid‐19 at a Comprehensive Cancer Center in a Covid‐19 hotspot area in Germany.
Methods
We performed a retrospective single center cohort study of 39 patients with hematological and solid cancers who were hospitalized at the University Hospital Freiburg for Covid‐19. Using univariate and multivariate Cox regression models we compared time to severe events and overall survival to an age‐matched control cohort of 39 patients with confirmed Covid‐19 without a cancer diagnosis.
Results
In the cancer cohort 29 patients had a diagnosis of a solid tumor, and 10 had a hematological malignancy. In total, eight patients (21%) in the cancer and 14 patients (36%) from the noncancer cohort died during the observation period. Presence of a malignancy was not significantly associated with survival or time to occurrence of severe events. Major influences on mortality were high IL‐6 levels at Covid‐19 diagnosis (HR = 6.95, P = .0121) and age ≥ 65 years (HR = 6.22, P = .0156).
Conclusions
Compared to an age‐matched noncancer cohort, we did not observe an association between a cancer diagnosis and a more severe disease course or higher fatality rate in patients with Covid‐19. Patients with a hematological malignancy showed a trend towards a longer duration until clinical improvement and longer hospitalization time compared to patients with a solid cancer. Cancer per se does not seem to be a confounder for dismal outcome in Covid‐19.
In this retrospective single center cohort study at a Comprehensive Cancer Center in Germany we did not observe an association between a cancer diagnosis and a more severe disease course or higher fatality rate in patients with Covid‐19 when compared to an age‐matched control cohort of patients with confirmed Covid‐19 without a cancer diagnosis.
Genetic susceptibility to lymphoma Skibola, Christine F; Curry, John D; Nieters, Alexandra
Haematologica (Roma),
07/2007, Volume:
92, Issue:
7
Journal Article
Peer reviewed
Open access
From the Division of Environmental Health Sciences, School of Public Health, 140 Warren Hall, University of California, Berkeley, CA 94720-7360, USA (CFS); Division of Immunology, Department of ...Molecular and Cell Biology, University of California, Berkeley, California 94720, USA (JDC); Division of Clinical Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany (AN)
Correspondence: Christine Skibola, Ph.D., School of Public Health, 140 Earl Warren Hall University of California, Berkeley, Ca. 94720-7360, USA. E-mail: chrisfs{at}berkeley.edu
ABSTRACT
Genetic susceptibility studies of lymphoma may serve to identify at risk populations and clarify important disease mechanisms. This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol intakes are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis. However, this links will need replication in larger populations. Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations.
Key words: lymphoma, genetic susceptibility, SNP, NHL, polymorphisms.
Background & Aims: Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the ...risk of non-Hodgkin’s lymphoma (NHL) subtypes after HCV infection. Methods: The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. Results: HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio OR, 1.78; 95% confidence interval CI, 1.40–2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44–4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68–2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14–5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65–1.60). Conclusions: These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).
Respiratory tract infections (RTIs) are the most common infections in patients with rheumatic diseases under immunosuppressive treatment and may contribute to morbidity and mortality as well as ...increased healthcare costs. However, to date only limited data on infection risk in spondyloarthritis (SpA) patients are available. In this study we assessed the occurrence of respiratory tract infections in a monocentric real-world cohort consisting of 330 patients (168 psoriatic arthritis and 162 axial spondyloarthritis patients) and determined factors associated with increased infection risk. Out of 330 SpA patients, 89.3% had suffered from ≥ 1 upper respiratory tract infection (URTI) and 31.1% from ≥ 1 lower respiratory tract infection (LRTI) within the last two years. The most common URTIs were rhinitis and laryngitis/pharyngitis with 87.3% and 36.1%, respectively. Bronchitis constituted the most common LRTI, reported in 29.7% of patients. In a multivariate binomial logistic regression model occurrence of LRTI was associated with chronic lung disease (OR 17.44, p=0.006), glucocorticoid therapy (OR 9.24, p=0.012), previous history of severe airway infections (OR 6.82, p=0.013), and number of previous biological therapies (OR 1.72, p=0.017), whereas HLA B27 positivity was negatively associated (OR 0.29, p=0.025). Female patients reported significantly more LRTIs than male patients (p=0.006) and had a higher rate of antibiotic therapy (p=0.009). There were no significant differences between axSpA and PsA patients regarding infection frequency or antibiotic use. 45.4% of patients had required antibiotics for respiratory tract infections. Antibiotic therapy was associated with smoking (OR 3.40, p=0.008), biological therapy (OR 3.38, p=0.004), sleep quality (OR 1.13, p<0.001) and age (OR 0.96, p=0.030). Hypogammaglobulinemia (IgG<7g/l) was rare (3.4%) in this SpA cohort despite continuous immunomodulatory treatment.
Awareness of these risk factors will assist physicians to identify patients with an increased infection risk, who will benefit from additional preventive measures, such as vaccination and smoking cessation or adjustment of DMARD therapy.
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