Severe α1-antitrypsin deficiency (PiZ homozygosity) with membranoproliferative glomerulonephritis and nephrotic syndrome, reversible after orthotopic liver transplantation

Background/Aims: Nephropathy associated with α₁-antitrypsin deficiency is assumed to be an unusual entity. We describe the case of a 23-year-old woman with severe α₁-antitrypsin (PiZ homozygosity) deficiency who developed hepatic cirrhosis in childhood, and glomerulonephritis and nephrotic syndrome in adult life.Methods/Results: A renal biopsy was consistent with membranosproliferative glomerulophritis. An immunofluorescence study revealed the presence of α₁-anti-trypsin (PiZ) in the subendothelial region of the glomerular basement membrane. The renal disease was reversible after orthotopic liver transplantation.Conclusions: The presence of abnormal PiZ protein in the subendothelial region of the glomerular basement membrane may suggest a possible role for this protein in the pathogenesis of glomerulonephritis. The case should add impetus to the search for α₁-antitrypsin deficiency in any patient presenting with combined liver and renal disease, in the absence of evidence of hepato-renal syndrome, and illustrates that liver transplantation alone may reverse the neophropathy associated with α₁-antitrypsin deficiency.     

Features of Everyday Life in Psychiatric Inpatient Care for Self-harming: An Observational Study of Six Women

This study aimed to describe the features of everyday life in psychiatric inpatient care as experienced by women who self-harm. Participant observations and informal interviews were conducted with six women and were subjected to qualitative content analysis. The major feature of everyday life in psychiatric inpatient care was ‘being surrounded by disorder’, which consisted of ‘living in a confusing environment, being subject to routines and rules that offer safety but lack consistency’ and ‘waiting both in loneliness and in togetherness’. The nursing staff spent minimal time with the patients and the women turned to each other for support, care and companionship.     

SYNERGISTIC RELATIONSHIPS AMONG STRESS,DEPRESSION, AND TROUBLED RELATIONSHIPS: INSIGHTS FROM PSYCHONEUROIMMUNOLOGY

Stress and depression consistently elevate inflammation and are often experienced simultaneously, which is exemplified by people in troubled relationships. Troubled relationships also elevate inflammation, which may be partially explained by their ability to engender high levels of stress and depression. People who are stressed, depressed, or in troubled relationships are also at greater risk for health problems than their less distressed counterparts. Inflammation, a risk factor for a variety of age‐related diseases including cardiovascular disease, Type II diabetes, metabolic syndrome, and frailty, may be one key mechanistic pathway linking distress to poor health. Obesity may further broaden the health implications of stress and depression; people who are stressed or depressed are often overweight, and adipose tissue is a major source of proinflammatory cytokines. Stress, depression, and troubled relationships may have synergistic inflammatory effects: loneliness, subclinical depression, and major depression enhance inflammatory responses to an acute stressful event. The relationship between distress and inflammation is bidirectional; depression enhances inflammation and inflammation promotes depression. Interesting questions emerge from this literature. For instance, some stressors may be more potent than others and thus may be more strongly linked to inflammation. In addition, it is possible that psychological and interpersonal resources may buffer the negative inflammatory effects of stress. Understanding the links among stress, depression, troubled relationships, and inflammation is an exciting area of research that may provide mechanistic insight into the links between distress and poor health.     

The human GIMAP5 gene has a common polyadenylation polymorphism increasing risk to systemic lupus erythematosus

Background

Several members of the GIMAP gene family have been suggested as being involved in different aspects of the immune system in different species. Recently, a mutation in the GIMAP5 gene was shown to cause lymphopenia in a rat model of autoimmune insulin‐dependent diabetes. Thus it was hypothesised that genetic variation in GIMAP5 may be involved in susceptibility to other autoimmune disorders where lymphopenia is a key feature, such as systemic lupus erythematosus (SLE).

Material and methods

To investigate this, seven single nucleotide polymorphisms in GIMAP5 were analysed in five independent sets of family‐based SLE collections, containing more than 2000 samples.

Result

A significant increase in SLE risk associated with the most common GIMAP5 haplotype was found (OR 1.26, 95% CI 1.02 to 1.54, p = 0.0033). In families with probands diagnosed with trombocytopenia, the risk was increased (OR 2.11, 95% CI 1.09 to 4.09, p = 0.0153). The risk haplotype bears a polymorphic polyadenylation signal which alters the 3′ part of GIMAP5 mRNA by producing an inefficient polyadenylation signal. This results in higher proportion of non‐terminated mRNA for homozygous individuals (p<0.005), a mechanism shown to be causal in thalassaemias. To further assess the functional effect of the polymorphic polyadenylation signal in the risk haplotype, monocytes were treated with several cytokines affecting apoptosis. All the apoptotic cytokines induced GIMAP5 expression in two monocyte cell lines (1.5–6 times, p<0.0001 for all tests).

Conclusion

Taken together, the data suggest the role of GIMAP5 in the pathogenesis of SLE.