Sex differences and genomics in autoimmune diseases

Amur, Shashi; Parekh, Ameeta; Mummaneni, Padmaja

doi:10.1016/j.jaut.2011.12.001

Cited by 106 publications

(66 citation statements)

References 129 publications

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“…50 The reason for the association of MTX-LD with Caucasian race and female gender identified in this study is unclear. Whether this is explained by inherent differences in susceptibility to MTX-related liver injury or merely reflects the predominance of females and Caucasians among patients with rheumatoid arthritis 75 and psoriasis, 76 respectively, requires further study.…”

Section: Discussionmentioning

confidence: 99%

End‐stage methotrexate‐related liver disease is rare and associated with features of the metabolic syndrome

Dawwas

Aithal

2014

Aliment Pharmacol Ther

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SummaryBackgroundMethotrexate (MTX) is one of the most frequently prescribed drugs in contemporary medicine with a well‐recognised hepatotoxic potential, for which stringent laboratory and histological surveillance has long been advocated.AimTo estimate the population burden of end‐stage methotrexate‐related liver disease (MTX‐LD) in the United States and identify independent host risk factors for this disease entity.MethodsWe analysed the records of all individuals who had been listed for, and/or received, liver transplantation in the United States, as reported to the Organ Procurement and Transplantation Network between 1 October 1987 and 31 December 2011, and identified those whose liver disease was attributed, wholly or partly, to MTX therapy. We also compared the demographic and clinical characteristics of adult individuals with MTX‐LD with those listed and/or transplanted for alcoholic liver disease (ALD, n = 43 285), non‐alcoholic steatohepatitis (NASH, n = 7569) and primary sclerosing cholangitis (PSC, n = 8526) using the adjusted odds ratios (AORs) derived from multi‐variable logistic regression models.ResultsOf 158 904 adults who had been listed for, and/or received, liver transplantation during the study period, only 117 (0.07%) had MTX‐LD. Compared with individuals with ALD and PSC, those with MTX‐LD were more likely to be older (AORs per 5‐year increase: 1.27, P < 0.001 and 1.33, P < 0.001 respectively); female (AORs: 1.78, P = 0.003 and 3.87, P < 0.001); Caucasian (AORs: 3.03, P = 0.001 and 2.05, P = 0.04); and diabetic (AORs: 2.76, P < 0.001 and 4.12, P < 0.001). With the exception of Caucasian ethnicity (AOR: 1.94, P = 0.05), the odds of these characteristics did not differ from individuals with NASH. The odds of elevated body mass index among MTX‐LD individuals were higher than those with PSC (AOR per 5 kg/m2: 1.51, P < 0.001); similar to those with ALD (AOR per 5 kg/m2:1.15, P = 0.1); and lower than those with NASH (AOR per 5 kg/m2: 0.66, P < 0.001).ConclusionsThe United States population burden of end‐stage methotrexate‐related liver disease is likely to be exceedingly small, suggesting the need for reappraisal of current hepatotoxicity surveillance guidelines. The risk factor profile of methotrexate‐related liver disease supports the notion that it may share a common pathogenesis with NASH.

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Section: Discussionmentioning

confidence: 99%

End‐stage methotrexate‐related liver disease is rare and associated with features of the metabolic syndrome

Dawwas

Aithal

2014

Aliment Pharmacol Ther

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“…SSc is more frequent in females than males, with a woman-to-man ratio ranging from 3:1 to 12:1 [3]. Nevertheless, despite this sex bias, a recent study has reported a correlation between male sex and a worse outcome of the disease [4].…”

Section: Systemic Sclerosis: a Complex Diseasementioning

confidence: 99%

Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

Bossini‐Castillo

López‐Isac

Martı́n

2015

Journal of Autoimmunity

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“…This increased level of immunity can be beneficial in protection against, and clearance of, a proportion of pathogens. However, it can also be detrimental, by increasing immunopathology in certain infectious diseases and by predisposing to autoimmune diseases [4]. The underlying mechanisms for these sexual dimorphisms are multifactorial, including the endocrine and genetic effects on the immune system and physiology, as well as sex-related differences in behavior.…”

mentioning

confidence: 99%

Sex Differences in Pediatric Infectious Diseases

Muenchhoff

Goulder

2014

Journal of Infectious Diseases

325

243

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The success of the immune response is finely balanced between, on the one hand, the need to engage vigorously with, and clear, certain pathogens; and, on the other, the requirement to minimize immunopathology and autoimmunity. Distinct immune strategies to achieve this balance have evolved in females and males and also in infancy through to adulthood. Sex differences in outcome from a range of infectious diseases can be identified from as early as fetal life, such as in congenital cytomegalovirus infection. The impact of sex hormones on the T-helper 1/T-helper 2 cytokine balance has been proposed to explain the higher severity of most infectious diseases in males. In the minority where greater morbidity and mortality is observed in females, this is hypothesized to arise because of greater immunopathology and/or autoimmunity. However, a number of unexplained exceptions to this rule are described. Studies that have actually measured the sex differences in children in the immune responses to infectious diseases and that would further test these hypotheses, are relatively scarce.

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Sex differences and genomics in autoimmune diseases

Cited by 106 publications

References 129 publications

End‐stage methotrexate‐related liver disease is rare and associated with features of the metabolic syndrome

End‐stage methotrexate‐related liver disease is rare and associated with features of the metabolic syndrome

Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

Sex Differences in Pediatric Infectious Diseases

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