Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

Objectives - To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS. Methods - Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis. Results - COMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009). Conclusions - Autonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity

Fatigue in primary Sjögren's syndrome (pSS) is associated with lower levels of proinflammatory cytokines: a validation study

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease with symptoms including dryness, fatigue, and pain. The previous work by our group has suggested that certain proinflammatory cytokines are inversely related to patient-reported levels of fatigue. To date, these findings have not been validated. This study aims to validate this observation. Blood levels of seven cytokines were measured in 120 patients with pSS from the United Kingdom Primary Sjögren’s Syndrome Registry and 30 age-matched healthy non-fatigued controls. Patient-reported scores for fatigue were classified according to severity and compared to cytokine levels using analysis of variance. The differences between cytokines in cases and controls were evaluated using Wilcoxon test. A logistic regression model was used to determine the most important identifiers of fatigue. Five cytokines, interferon-γ-induced protein-10 (IP-10), tumour necrosis factor-α (TNFα), interferon-α (IFNα), interferon-γ (IFN-γ), and lymphotoxin-α (LT-α) were significantly higher in patients with pSS (n = 120) compared to non-fatigued controls (n = 30). Levels of two proinflammatory cytokines, TNF-α (p = 0.021) and LT-α (p = 0.043), were inversely related to patient-reported levels of fatigue. Cytokine levels, disease-specific and clinical parameters as well as pain, anxiety, and depression were used as predictors in our validation model. The model correctly identifies fatigue levels with 85% accuracy. Consistent with the original study, pain, depression, and proinflammatory cytokines appear to be the most powerful predictors of fatigue in pSS. TNF-α and LT-α have an inverse relationship with fatigue severity in pSS challenging the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10^{-8}; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10^{−10}; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

\ua9 2021, The Author(s).Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 7 10−8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 7 10−10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)