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D J Unsworth

Publications and source records attributed to D J Unsworth.

At least 19 recordsLinked to original sources
PubMed2006

HLA Cw*06 is not essential for streptococcal-induced psoriasis.

BACKGROUND: Streptococcal throat infections and HLA Cw6 (Cw*06) have been implicated in the pathogenesis of psoriasis, particularly in the guttate form. OBJECTIVES: To study 105 Irish patients with psoriasis to investigate the relationship between streptococcal infections and Cw*06. METHODS: The patients were divided into two groups: those with guttate psoriasis or guttate flare (guttate group, GG, n=64) and those with chronic plaque psoriasis (chronic plaque group, CPG, n=41). RESULTS: The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different (P=0.1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) (P<0.0001 vs. GG and P<0.0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) (P=0.0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype. CONCLUSIONS: Thus, not all patients with streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if any, has yet to be determined.

Adolescent↗
PubMed2005

Ataxia, peripheral neuropathy, and anti-gliadin antibody. Guilt by association?

Some authors contend that patients with idiopathic neurological disease who are also anti-gliadin antibody seropositive are gluten sensitive. However, anti-gliadin antibodies lack disease specificity being found in 10% of healthy blood donors. We report a study comparing anti-gliadin antibody with other food antibodies in patients with idiopathic ataxia (20), hereditary ataxias (seven), or idiopathic peripheral neuropathy (32). Patients were HLA typed. IgA anti-tissue transglutaminase antibodies (tTG) were measured. No case was positive for IgA anti-tTG making occult coeliac disease unlikely. HLA DQ2 and HLA DQ8 were found distributed equally across all patient groups and unrelated to gliadin antibody status. HLA DQ2 expressing, anti-gliadin antibody positive cases (so called "gluten ataxia") were rare in our clinics (four cases in 2 years from a population of 2 million). We conclude that coeliac disease per se is not commonly associated with either idiopathic ataxia or idiopathic peripheral neuropathy. Our study also casts doubt on the nosological status of "gluten ataxia" as a discreet disease entity. All food antibodies tested, particularly IgG, were a common finding in both ataxia and peripheral neuropathy groups. No particular food antibody was associated with any patient group. Food antibodies were equally common in hereditary ataxias. We conclude they are a non-specific finding.

Adult↗
PubMed2004

Echocardiographic abnormalities in primary antibody deficiency.

OBJECTIVE: To document cardiac abnormalities secondary to pulmonary disease in primary antibody deficiency. PATIENTS AND METHODS: A cross sectional audit study of patients from a regional immunology centre. Subjects undergoing two dimensional and Doppler transthoracic echocardiography were reviewed. Ventricular dimensions and function, valvular competence, and estimated pulmonary artery pressure were recorded. Data were compared with clinical variables, pulmonary function tests, and thoracic computed tomography data. RESULTS: Nineteen patients with common variable immunodeficiency and one with IgG(2) subclass deficiency were included, mean age at diagnosis 37.5 years, mean estimated diagnostic delay 10.94 years. Left ventricular impairment was found in 15% and right heart dilatation in 20%. Pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) was found in 45% (9/20), graded as moderate (40-60 mm Hg) in 44% of cases. Pulmonary function was obstructive in 47% (9/19). Fifty five percent of the patients with computed tomography data within the last five years (10/18) had confirmed bronchiectasis. Patients with right heart dilatation and/or moderate pulmonary hypertension (n = 6) had a more prolonged diagnostic delay (p = 0.04) and more severe lung disease. CONCLUSION: Echocardiographic abnormalities are common in primary antibody deficiency, associated with diagnostic delay and pulmonary complications. Pulmonary hypertension should be considered in those with severe lung disease and can be confirmed by echocardiography.

Adult↗
PubMed2003

Misdiagnosis of hereditary angio-oedema type 1 and type 2.

BACKGROUND: Hereditary angio-oedema is a rare, life-threatening, autosomal dominant condition caused by deficiency (type 1) or dysfunction (type 2) of complement C1 inhibitor. Serological assays to measure C1 inhibitor concentration and function are widely available. However, expert interpretation may not be. OBJECTIVE: To review all cases within three NHS Trusts with a putative diagnosis of hereditary angio-oedema. METHOD: Review of laboratory results and clinical notes of 44 cases of presumed hereditary angio-oedema. RESULTS: Audit revealed that 11 of 42 (26%) cases had been incorrectly considered to have a diagnosis of hereditary angio-oedema. Two of 44 had insufficient data to assess. All 11 had low functional C1 inhibitor recorded at presentation. RESULTS: available in these 11 cases at the time of diagnosis showed a normal or borderline C4 level (>or= 50% of mean normal, in contrast to hereditary angio-oedema, where C4 was less than 40% of mean normal) indicating that the low C1 inhibitor levels were a result of sample decay. Cases incorrectly diagnosed were predominantly female and had a mean age at presentation of 40 years (compared with 22 years for type 1 hereditary angio-oedema). Six of the 11 cases were offered C1 inhibitor concentrate (pooled plasma product) as treatment. CONCLUSION: We recommend that all suspected cases of hereditary angio-oedema are reviewed, that specialist advice is sought before making the diagnosis and that the diagnosis is only made after initial abnormal serology is confirmed on a second sample.

Adolescent↗
PubMed2003

The immunopathogenesis of meningococcal disease.

This review describes the mechanisms of the immune response to meningococcal disease, examining the extent to which individual variation of the immune response can determine susceptibility. It concludes by summarising the difficulties encountered by recent efforts to develop new immunomodulatory treatments.

Carrier State↗
PubMed2003

Pneumocystis carinii, cytomegalovirus, and severe transient immunodeficiency.

Pneumocystis carinii infection is rare in infants, and raises strong concerns of immune deficiency. This report describes the unusual case of a male infant with concurrent chest infections caused by P carinii and cytomegalovirus. Investigation was complicated by the strong suspicion of non-accidental injury, including subdural haematomas. The case illustrates how to investigate for possible immunodeficiency. Low immune function tests at presentation slowly improved and have remained normal on longterm follow up. Possible explanations for the transient severe clinical immunodeficiency in this case are discussed.

Anti-Bacterial Agents↗
PubMed2003

Immunoglobulins and immunoglobulin subclasses in the elderly.

BACKGROUND: Published data imply that adult concentrations are achieved for all Ig isotypes and plateau by 15-18 years of age. Recent data, however, suggest that these results are not applicable in the elderly. There are no equivalent data for IgG subclasses. We present reference range data for an elderly UK patient population, for IgG, IgA, IgM and IgG subclasses. METHODS: Serum immunoglobulins were reviewed on samples from 1146 patients > 60 years of age and 925 patients aged 18-60 years. Serum IgG subclasses were reviewed on samples from 498 patients >60 years and 484 patients aged 18-60 years. All Igs and subclasses were measured by nephelometry. Reference ranges were derived by probability plotting. RESULTS: Serum median IgG and IgM concentrations are reduced in the elderly (IgG female P < 0.001, IgG male P < 0.03; IgM female P < 0.001, IgM male P < 0.001). Serum IgA concentrations are maintained. Indeed, men showed a slight increase in serum IgA with age (P = 0.03). Few differences dependent on gender were seen. Median IgM was lower in men in the younger age groups (18-60 years P < 0.001; 61-70 years P = 0.017). IgG(2) is reduced in elderly men (P = 0.002) and IgG, reduced in elderly women (P = 0.009). CONCLUSIONS: We advocate that centres offering these investigations provide local, method-dependent reference ranges, and suggest an approach as to how this might be achieved.

Adolescent↗
PubMed2002

Dermatitis herpetiformis and neurological dysfunction.

Dermatitis herpetiformis and coeliac disease are gluten sensitive diseases, which have common immunopathological and genetic mechanisms. Neuropsychiatric complications have been reported in up to 26% of patients with coeliac disease. This is probably an overestimate, because of the chance associations with some common neurological conditions such as epilepsy. The pathogenesis is speculative but it has been postulated that gluten is neurotoxic possibly via immune mechanisms. The frequency of neurological dysfunction in patients with dermatitis herpetiformis has not been characterised. Patients with dermatitis herpetiformis might be expected to be particularly susceptible to neuronal damage as some continue to consume gluten when their dermatological symptoms are controlled by dapsone. Thirty five patients were recruited with dermatitis herpetiformis from dermatology clinics at St Mary's Hospital, London and Queen's Medical Centre, Nottingham and investigated for evidence of neurological abnormality. All patients underwent a full neurological examination and were asked about their neurological and general medical history by means of a structured questionnaire. Serum samples were taken and screened for the presence of anti-neuronal antibodies (anti-Hu and Yo) as well as anti-gliadin (IgA and G) anti-endomysial (IgA), and anti-tissue transglutaminase (IgA) antibodies. Neurophysiological tests were carried out where appropriate. Only two patients were identified with unexplained neurological abnormalities (one essential tremor, and one chorea). Two other patients had a history of migraine. The patient with chorea also had borderline/equivocally positive anti-Hu antibodies by immunofluorescence assay. All other samples were negative for anti-neuronal antibodies. Fifteen patients were positive for anti-gliadin antibodies (IgA and/or IgG), four for anti-endomysial antibodies (monkey oesophagus or umbilical cord), and six for anti-tissue transglutaminase antibodies. The presence of these antibodies did not correlate with the presence of neurological abnormalities. No cases of "gluten ataxia" were identified. In conclusion, there was no convincing evidence for immune mediated neurological damage in this pilot study of dermatitis herpetiformis.

Adolescent↗
PubMed2001

Wiskott-Aldrich syndrome, vasculitis and critical aortic dilatation.

UNLABELLED: Wiskott-Aldrich syndrome is a rare X-linked disorder, comprising the triad eczema, thrombocytopenia and progressive immunodeficiency. The prognosis has been poor in the past but is now improving with therapeutic options including splenectomy and bone marrow transplantation. We report the case of a 21-year-old male with an established diagnosis of Wiskott-Aldrich syndrome, who developed aortic root dilatation with severe aortic regurgitation requiring aortic valve and root replacement. Histology confirmed a destructive, full-thickness, chronic aortitis. CONCLUSION: As treatment and prognosis improve, large vessel vasculitis may become an increasingly recognized late complication of this syndrome, which now extends into adult practice.

Adult↗
PubMed2001

Antibodies to extractable nuclear antigens. Has technological drift affected clinical interpretation?

Precipitating antibodies to extractable nuclear antigens are important in the diagnosis of connective tissue diseases. Disease associations are defined using gel based techniques. Alternative technologies have been introduced, including passive haemagglutination, enzyme linked immunosorbent assay, and western blotting. This leader contains a review of the literature on the clinical usefulness of these assays, together with knowledge gained from personal experience. Using the example of systemic lupus erythematosus, the sensitivity, specificity, and positive predictive value of the assays for disease is discussed, as is their differences in performance. The conclusion drawn is that disease specificity is method dependent. Validation and audit of performance of the method selected by the investigation laboratory is essential.

Antibodies, Antinuclear↗
PubMed2001

The high prevalence of autoantibodies to tissue transglutaminase in first-degree relatives of patients with type 1 diabetes is not associated with islet autoimmunity.

OBJECTIVE: To determine the extent of celiac autoimmunity in type 1 diabetic patients and the overlap between islet and celiac autoimmunity in their nondiabetic relatives. RESEARCH DESIGN AND METHODS: IgA antibodies to tissue transglutaminase were determined in serum taken from 433 type 1 diabetic patients and 1,442 nondiabetic first-degree relatives. Samples with transglutaminase antibodies above the 97.5th percentile of 347 schoolchildren were also assayed for IgA anti-endomysial antibodies (EMAs). Markers of islet autoimmunity (islet cell antibodies and autoantibodies to insulin, glutamate decarboxylase. and protein tyrosine phosphatase IA-2) had previously been measured in all relatives. RESULTS: In the absence of known celiac disease, the prevalence of transglutaminase antibody levels above the 97.5th percentile of the schoolchildren was 13.4% in diabetic patients and 7.0% in nondiabetic relatives. ENMAs were found in addition to transglutaminase antibodies in 2.6% of probands and in 1.9% of first-degree relatives, but none of the schoolchildren. Transglutaminase antibodies were found to persist in 10 of 30 patients and in 30 of 59 relatives with follow-up samples taken at least 2 years after the initial sample. Of 186 nondiabetic relatives with islet autoantibodies, only 10 also had transglutaminase antibodies. CONCLUSIONS: We found a high prevalence of celiac autoimmunity in patients and first-degree relatives of children with type 1 diabetes, but we found limited overlap between islet and celiac autoimmunity in nondiabetic relatives. The high prevalence of celiac autoimmunity may be explained by shared genetic susceptibility and identifies a population within which screening for the disease may be justified.

Adolescent↗
PubMed2001

Diagnosing coeliac disease by rectal gluten challenge: a prospective study based on immunopathology, computerized image analysis and logistic regression analysis.

The purpose of this study was to evaluate the use of rectal gluten challenge in the diagnosis of coeliac disease. A total of 103 patients with features suggestive of this diagnosis were prospectively enrolled into the study; a diagnosis of coeliac disease was based on strictly defined criteria used in judging the proximal jejunal biopsy. On that basis, 45 out of the 103 patients were deemed to have coeliac disease. A slurry of gluten powder in physiological saline was introduced into the rectum, and biopsies taken before and at 2 h or 4 h after the challenge were examined immunohistochemically by computerized image analysis. Cell counts were analysed by logistic regression, and the best equations were obtained for each challenge group. The 2 h challenge yielded diagnostic sensitivity and specificity of 69.6% and 78.6% respectively. The 4 h challenge provided sensitivity and specificity of 100% and 100% respectively. These results were compared with other clinical diagnostic predictors,including anti-endomysial antibodies, which yielded diagnostic sensitivity and specificity of 70% and 98% respectively. It is concluded that a 4 h rectal challenge is a highly sensitive means of identifying gluten-sensitized individuals, and would be of particular value in cases showing negative antibody screening or equivocal biopsy appearances.

Adult↗
PubMed2001

Coeliac disease, anaemia and pregnancy.

We have investigated the prevalence of positive serology for coeliac disease in pregnant women, using the IgA anti-endomysium antibody test. Five of 216 pregnant women with a haemoglobin less than 11 g/dl were positive, compared to 0/350 with haemoglobin > or = 11 g/dl. Four of these five had low plasma ferritin levels, indicative of iron deficiency anaemia; the fifth was borderline normal. We found no association between positive coeliac disease serology and folate deficiency. None of thirty mothers of children born with neural tube defects were IgA anti-endomysium antibody positive. This study has identified a very high prevalence of occult coeliac disease in pregnancy and a strong association with anaemia. We advise that in cases with a haemoglobin of less than 11 g/dl in pregnancy, coeliac disease should be excluded.

Adolescent↗
PubMed2000

Type 1 diabetes mellitus masking primary antibody deficiency.

A patient with a history of recurrent cutaneous and pulmonary infections, nephrotic syndrome, and an established diagnosis of type 1 diabetes was found to have unsuspected and unrecognised primary immunodeficiency. On review of the case, previous investigations pointed to the correct diagnosis over 10 years earlier. This combination of diagnoses has not previously been reported. The patient is now well on replacement intravenous immunoglobulin therapy, urinary loss of IgG having been specifically excluded before treatment. This case highlights how antibody deficiency can easily be missed despite an obvious infection history unless results are interpreted carefully and in context.

Adult↗