Autoimmune Diseases: Contributing Factors, Spec... \/\/FREE\\\\
Venous thromboembolism (VTE) is major health problem and is sometimes complicated by lethal pulmonary embolism (PE). Disturbances of the coagulation and anticoagulation systems are important risk factors for VTE. Comparative studies suggest that coagulation and innate immunity have a shared evolutionary origin. It is therefore unsurprising that the immune and coagulation systems are linked, with many molecular components being important for both systems. Systemic inflammation modulates thrombotic responses by suppressing fibrinolysis, upregulating procoagulant, and downregulating anticoagulants, and autoimmune disorders such as systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and Behçet's syndrome have been linked to an increased risk of VTE. Recent reports have further shown that a majority of autoimmune and immune-mediated disorders are linked to an increased risk of venous thrombosis, PE, or VTE. For instance, a Swedish nationwide study found that the risk of PE was increased in the first year after hospitalization for 33 different autoimmune disorders. Especially high risks were noted for several autoimmune diseases such as immune thrombocytopenic purpura, polyarteritis nodosa, polymyositis/dermatomyositis, ulcerative colitis, and SLE. Another study from England, also based on hospitalization data, found that immune-mediated disorders were associated with an increased risk of VTE compared with other medical causes of hospitalization. Multiple mechanisms may operate and disease-specific factors, such as cardiolipin antibodies, have been identified. However, inflammation by itself appears to change the hemostatic balance in a thrombogenic direction. Recent epidemiological studies, together with previous experimental and clinical studies, indicate that autoimmune disorders should not only be viewed as inflammatory disorders, but also hypercoagulable disorders. Research to identify thrombotic risk factors, elucidate the mechanisms involved, and investigate prophylactic regiments is needed. The present review describes the epidemiological, clinical, and experimental evidence for the connection between VTE and autoimmune and immune-mediated disorders.
Autoimmune Diseases: Contributing Factors, Spec...
Summary of autoimmune/inflammatory disorders consistently associated with risk of malignant lymphomas, including reported RR range, disease-related risk factors, associated lymphoma subtypes, and future research issues
It is conceivable that sustained antigen-driven B-cell proliferation may increase the risk of adverse genetic events, ultimately leading to the emergence of a neoplastic clone. The effect of such events could be enhanced by acquired resistance to apoptosis in autoimmune disorders (147). In RA and SLE, apoptotic resistance is increased and mediated by Bcl-2 expression, activation of nuclear factor-κB by inflammatory cytokines and growth factors, and abnormalities in the expression of B-cell activating factor (BAFF/BLyS, a member of the TNF superfamily; refs. 147, 148). Patients with Sjögren's syndrome, RA, and SLE have increased levels of BAFF in serum and synovial fluid (149), and BAFF levels in Sjögren's syndrome patients correlate with the level of disease-specific autoantibodies (149). B-cell activating factors have also been implicated in the growth and survival of B-cell malignancies (150). In one study, serum levels of BAFF were on average 3-fold higher in follicular lymphoma patients than in controls (151). Other cytokines of potential importance include (IL)-6 and IL-10 and TNF-α. IL-10 mediates autoantibody production and may function as an autocrine growth factor in B-cell lymphomas (152). Apart from being a key inflammatory mediator in RA and other inflammatory diseases, TNF is also a growth factor for lymphoma. Recently, in a pooled analysis within a large lymphoma study consortium (InterLymph; ref. 153), genetic variation in the TNF-α and IL-10 genes was associated with an up to 2-fold increased risk of diffuse large B-cell lymphoma, the subtype particularly associated with several autoimmune disorders in other studies (23, 25, 51, 65). Interestingly, variation in TNF-α and related receptor genes may also increase susceptibility to SLE and Sjögren's syndrome (154). In another study, IL-10 and IL-4 polymorphisms were modestly but significantly associated with NHL risk (155), leading the authors to speculate that abnormalities in the T helper (TH) cell type 2 immune response enhance lymphomagenesis. Autoimmune disorders are also associated with alterations in the TH cell response, although in various ways. RA, sarcoidosis, and psoriasis are characterized by accumulation of TH1 lymphocytes, SLE by a TH2 response (156), and Sjögren's syndrome by high serum levels of both TH1 and TH2 cytokines (157). Therefore, an altered TH1/TH2 balance does not in itself explain why some but not other autoimmune disorders are associated with increased lymphoma occurrence.
The notion of immunological pathways playing a role in the etiology of a subset of psychotic disorders has received increased interest in the last decades. One of the findings that has spiked interest herein, is an apparent link between autoimmune diseases and psychotic disorders. This is supported by genetic findings associating immune-related genetic markers with schizophrenia and clinical studies finding increased levels of inflammatory markers in patients with psychosis. Several large-scale epidemiologic studies have found positive associations between autoimmune diseases and psychosis. Particularly, autoimmune diseases as multiple sclerosis and lupus are known to have higher frequencies of neuropsychiatric symptoms, including psychosis, compared to healthy controls. Cross sectional studies have found higher prevalence of psychiatric diagnoses among those with autoimmune diseases, and longitudinal studies have shown bidirectional associations between several autoimmune diseases and increased risks associated with schizophrenia. Moreover, a family history of autoimmune diseases has been shown to be associated with an increased risk of psychotic disorders and vice versa. In this review we will summarize the epidemiologic evidence on associations between autoimmune diseases and psychosis. Possible mechanisms accountable for the association will be discussed, amongst others the probable role of shared genetic risk factors, the impact of infections on both autoimmunity and the development of psychotic disorders, and the potential role of the microbiome. We discuss the findings on and influence of autoantibodies and dysregulation of T- and B-cells in both disease categories, and why further research hereon is needed. In addition to the potential importance of autoimmunity in etiological mechanisms of psychotic disorders, the association also brings important attention to somatic comorbidity in patients with psychotic disorders.
A total of 284 studies were included. The findings were divided into nine main categories: (1) genetics, (2) gastrointestinal microbiota and autoimmune reactions, (3) childhood and early adolescent exposures, (4) personality traits and comorbid mental health conditions, (5) gender, (6) socio-economic status, (7) ethnic minority, (8) body image and social influence, and (9) elite sports. A substantial amount of research exists supporting the role of inherited genetic risk in the development of eating disorders, with biological risk factors, such as the role of gut microbiota in dysregulation of appetite, an area of emerging evidence. Abuse, trauma and childhood obesity are strongly linked to eating disorders, however less conclusive evidence exists regarding developmental factors such as role of in-utero exposure to hormones. Comorbidities between eating disorders and mental health disorders, including personality and mood disorders, have been found to increase the severity of eating disorder symptomatology. Higher education attainment, body image-related factors, and use of appearance-focused social media are also associated with increased risk of eating disorder symptoms.
Psychological risk factors, such as long-term stress, lack of social support, anxiety, and depression are important risk factors for neck pain. In terms of the biological risks, neck pain might occur as a consequence of certain diseases, such as neuromusculoskeletal disorders or autoimmune diseases. There is also evidence that demographic characteristics, such as age and sex, can influence the prevalence and development of neck pain, although further research is needed.
The burden of Hodgkin lymphoma varies with gender sex, age, and geographical location. People with a higher risk of Hodgkin lymphoma include males [1], adolescents and young adults [4], those with past history of Epstein-Barr virus infection [6], HIV/AIDS [7], autoimmune diseases [8], exposure to pollution [9], cigarette smoking [10], and family history. It was also found that the incidence of Hodgkin lymphoma varied by family size and socio-economic status [8]. Since the epidemiology of Hodgkin lymphoma is different across regions and may have changed over time, its global distribution pattern, risk factors, and temporal trends need to be assessed for developing tailored preventive measures for individual countries.
There are some limitations to this study. First, because of the poor infrastructure and cancer reporting mechanism in developing countries, there could be underestimations of the incidence and mortality of Hodgkin lymphoma in those countries. Also, overestimation could be a problem for some countries as the numbers were represented by the cancer registries of the major cities. Secondly, the risk factors association analysis was conducted at a population level. The findings may not apply to individuals. Besides, other important risk factors for Hodgkin lymphoma had not been considered in the analysis, including prevalence of Epstein-Barr virus infection, HIV/AIDS, and autoimmune diseases. Although comparisons of Hodgkin lymphoma incidence and mortality were made within the same regions according to age and sex group in this study, it could be challenging to directly compare different countries from the cancer registry that might change over time. Fourthly, some countries did not provide publicly available data on mortality although incidence data were reported, which have limited the analysis on relationship between incidence and mortality. In addition, trend analysis on subtypes of Hodgkin lymphoma was not performed due to data constraints. The disease distribution, risk factors, and temporal trends could be different among different subtypes of Hodgkin lymphoma, which could provide further insight into preventive measures of the disease. 041b061a72