Autoantibodies to glutathione S-transferase theta 1 in patients with primary sclerosing cholangitis and other autoimmune diseases

Primary sclerosing cholangitis (PSC) is an enigmatic disorder with a suggested autoimmune basis. A variety of autoantigens have been suggested but no specific or highly directed epitope has been identified. To address this issue, we constructed a cDNA library from normal human choledochus and screened expressing clones with serum from a patient with PSC and inflammatory bowel disease (IBD). Based on this screening, glutathione S-transferase theta 1 (GSTT1) was identified as a potential autoantigenic target. To study the specificity of GSTT1, we determined immunoreactivity using a panel of 58 patients with PSC, with and without IBD, 57 patients with IBD, 31 patients with Hashimoto's thyroiditis, 30 patients with primary biliary cirrhosis (PBC), 20 patients with insulin dependent diabetes mellitus, 22 patients with autoimmune polyendocrine syndrome type I, 10 patients with systemic lupus erythematosus (SLE), 20 patients with Sjögren's syndrome, 12 patients with autoimmune pancreatitis, 28 patients with Addison's disease, 27 patients with Grave's disease, 17 with myasthenia gravis, and 118 healthy controls. Reactivity against GSTT1 was found with PSC and IBD as well as some patients with other autoimmune pathology, indicating that this population of antibodies is neither specific nor a sensitive serologic marker for PSC, but the frequency was clearly higher in autoimmune patients than controls. GSTT1-antibodies have been described in persons with GSTT1-null genotype and are suggested to develop as an alloimmune response to blood transfusions from GSTT1-positive donors or pregnancies with GSTT1-positive children. Therefore, two IBD patients with and 15 PSC patients without GSTT1-antibodies were genotyped for GSTT1 to investigate if the presence of GSTT1-antibodies was associated with the GSTT1-null genotype and possibly caused by an alloimmune response. Both IBD patients and three of the PSC patients were of the GSTT1-null genotype. We note that the frequency of GSTT1-antibodies in this study is more than 100-fold higher than the frequency described earlier in patients with autoimmune diseases. We also observe an increased frequency of GSTT1-antibodies in patients with autoimmune diseases compared to healthy controls. This increased frequency can be explained by an autoimmune phenotype which increases susceptibility to such autoantibodies, or by a high frequency of the GSTT1-null genotype in autoimmune disease.     

The psychiatric sequelae of burn injury

Objective

To examine factors predicting psychiatric morbidity, taking into account the full range of psychiatric disorders before and after burn injury.

Methods

A cohort of 107 patients consecutively admitted to a Swedish national burn center was examined for lifetime psychiatric morbidity, as well as 94 patients at 1 year postinjury. Sixty-seven individuals, some from that same cohort, were interviewed at 2 to 7 years postinjury. The predictive effects of psychiatric history, personality and other risk factors for psychiatric morbidity following burn were evaluated with multiple regression analyses.

Results

The prevalence of having a psychiatric disorder preburn was 57%. One year postinjury 19% had minor or major depression and 23% had subsyndromal or full posttraumatic stress disorder. At 2 to 7 years, 31% fulfilled the criteria for a psychiatric disorder. The strongest contributing factors were a history of psychiatric morbidity and neuroticism.

Conclusions

Two-thirds of the patients had a lifetime psychiatric disorder, and one-third had a psychiatric diagnosis 2 to 7 years postburn. Mental health problems can have a major impact on daily life and functional abilities. Thus, identification and treatment of a range of psychiatric disorders, taking into account preburn psychiatric disorders and personality, is important for optimal adjustment after burn.     

Validation of the EQ-5D questionnaire in burn injured adults

Background

Health-related quality of life (HRQoL) is an important aspect of adaptation after burn. The EQ-5D is a standardized generic instrument for assessing HRQoL. Its psychometric properties in a group of burn injured individuals are, however, not known.

Methods

Seventy-eight consecutive patients admitted to a burn unit were included in a prospective longitudinal study. The participants completed the EQ-5D during acute care, and at 3, 6, and 12 months after the burn. At 6 and 12 months after the burn they also completed the Short-Form 36 Health Survey (SF-36) and the Burn Specific Health Scale-Brief (BSHS-B).

Results

High feasibility of the EQ-5D was demonstrated through a high response rate and a low proportion of missing or invalid answers. The floor and ceiling effects were small. Construct validity was demonstrated through good differentiation between health states and good discrimination of health states over time. The EQ-5D was associated with burn severity and discriminated between clinical subgroups in an expected manner. Criterion validity was demonstrated through significant correlations between the EQ-5D and subscales of the SF-36 and the BSHS-B.

Conclusions

The EQ-5D has good psychometric properties, it is short and easy to administer and thus useful in assessment of HRQoL after burn.     

Application and validation of the barrow neurological institute screen for higher cerebral functions in a control population and in patient groups commonly seen in neurorehabilitation.

OBJECTIVE: To determine whether the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) can differentiate brain-dysfunctional patients from controls. DESIGN: A case-control study. SUBJECTS: A total of 92 controls and 120 patients from a neuro-rehabilitation clinic with a diagnosis of: right and left hemisphere stroke, traumatic brain injury, Parkinson's disease or anoxic brain damage. METHODS: The BNIS has a maximum total score of 50 points, < 47 indicates cognitive dysfunction. Group comparisons and exploration of variables influencing the BNIS total score were made. RESULTS: A significant difference was found between the control group and the total patient group for the BNIS total score and for the subscales (p < 0.0005). Sensitivity was 88% and specificity 78%. Presence of disease and educational level had the greatest influence on the results of the BNIS. Patients with Parkinson's disease were shown to be the least cognitively affected and those with anoxic brain damage the most affected. CONCLUSION: The BNIS has potential value as a screening instrument for cognitive functions and is sufficiently sensitive to differentiate brain-dysfunctional patients from a control population. It appears to be applicable in a neurological rehabilitation setting, and can be used early in the process, giving a baseline cognitive functional level.