Are patient educational resources effective at deterring stroke survivors from considering experimental stem cell treatments? A randomized controlled trial.

OBJECTIVE: To evaluate whether online resources developed to educate people about the risks associated with experimental stem cell (SC) treatments influence stroke survivors' attitudes about the safety and effectiveness of these treatments. METHODS: Adult stroke survivors who had not previously received SC treatments (N = 112) were recruited from international stroke advocacy/support groups for a prospective, parallel-group randomized controlled trial. Participants indicated whether they were considering SC treatments (yes/no) prior to, immediately following, and 30-days after reading/viewing the International Society for Stem Cell Research booklet or Stem Cell Network video. Participant attitudes regarding the safety, effectiveness, accessibility and affordability of SC treatments were examined on each occasion, and compared to those of a waitlist control group. RESULTS: Significantly fewer participants were considering SC treatments immediately after reading the SC research booklet (p =.031), although neither intervention had any impact after 30-days (p >.05). Waitlist and intervention groups reported positive attitudes toward SC treatments at each assessment. CONCLUSIONS: Stroke survivor attitudes toward SC treatments were initially influenced by the patient booklet, however these changes were not maintained. PRACTICAL IMPLICATIONS: Clinicians are encouraged to initiate discussions about experimental SC treatments during inpatient rehabilitation and to reinforce the risks throughout subsequent care.

Laboratory clues to immunodeficiency; missed chances for early diagnosis?

Primary immunodeficiency is seen in an estimated one in 1200 people, and secondary immunodeficiency is increasingly common, particularly with the use of immunosuppresion, cancer therapies and the newer biological therapies such as rituximab. Delays in the diagnosis of immunodeficiency predictably lead to preventable organ damage. Examples of abnormal pathology tests that suggest immunodeficiency from all laboratory specialities are given, where vigilant interpretation of abnormal results may prompt earlier diagnosis. If immunodeficiency is suspected, suggested directed testing could include measuring immunoglobulins, a lymphocyte count and T-cell and B-cell subsets.

Immunoglobulin A deficiency on serological coeliac screening: an opportunity for early diagnosis of hypogammaglobulinaemia.

We present a serendipitous case of clinically significant pan-hypogammaglobulinaemia, diagnosed after routine serological testing for possible coeliac disease led first to identification of IgA deficiency (discovered as a low background in IgA-based routine serological screening), and subsequently to confirmed pan-hypogammaglobulinaemia (antibody immunodeficiency). Hypogammaglobulinaemia is a relatively rare diagnosis (estimated at 1 in 36,000), in which delayed diagnosis and treatment are associated with chronic organ damage including bronchiectasis. Routine serological testing for coeliac disease using the IgA anti-tissue transglutaminase (IgA TTG) test is in widespread use and provides an opportunity for early diagnosis of hypogammaglobulinaemia. Routine serological screening for coeliac disease may uncover IgA deficiency, and we suggest that all IgA-deficient cases identified should also be checked for antibody deficiency by quantifying the other immunoglobulins (IgG, IgM).

Unscrambling Egg Allergy: The Diagnostic Value of Specific IgE Concentrations and Skin Prick Tests for Ovomucoid and Egg White in the Management of Children with Hen's Egg Allergy.

Resolution of egg allergy occurs in the majority of egg allergic children. Positive specific IgE antibodies to ovomucoid (OVM) have been suggested to be of greater predictive value for persistent egg allergy than specific IgE to egg white. The performance of OVM-specific IgE antibody levels in a cohort of children referred for a routine egg challenge was compared with egg white specific IgE levels in predicting a positive egg challenge. 24/47 subjects had persistent egg allergy. Receiver operating characteristic analysis showed that OVM-specific IgE testing was the most useful test for the diagnosis of persistent egg allergy. The optimal decision points for the prediction of persistent egg allergy were >0.35 kUA/L for specific IgE levels to both EW and OVM, and ≥3 mm for SPT. Children with specific IgE levels suggestive of persistent egg allergy need not be subject to an egg provocation challenge, reducing both costs and risks to the child.

HLA and kidney transplantation.

This article focuses on the immunogenetics, immunology, rejection and immunosuppression in kidney transplantation. HLA matching still affects outcome data, and HLA matching improves graft survival. Graft sources and related outcomes are discussed.

Complement deficiency and disease.

There are approximately 30 serum complement proteins (15% of the globulin fraction), excluding cell surface receptors, and regulatory proteins. Many are manufactured in the liver, and reduced complement is a feature of severe liver failure. Complement proteins contribute to the acute phase response, and high levels are seen in chronic untreated inflammation (eg, rheumatoid arthritis). Once activated, complement is strongly pro-inflammatory. Indeed, almost half of the complement system proteins/receptors play regulatory roles, reflecting the importance of controlling inappropriate activation. This review focuses on disease states arising as a direct consequence of complement deficiency or dysfunction.

Pitfalls in the performance and interpretation of clinical immunology tests.

A broad overview, with examples, of the potential pitfalls encountered in the clinical immunology laboratory is presented. Illustrative examples and case scenarios are provided from autoimmunity, immunochemistry and cellular immunology, looking at both technical and interpretative pitfalls.

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.

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.

Life-threatening acute pulmonary haemorrhage in primary Sjögren's syndrome with cryoglobulinaemia.

We describe a woman with primary Sjögren's syndrome who presented with an acute pulmonary-renal syndrome resulting from cryoglobulinaemic vasculitis. Pulmonary manifestations of Sjögren's syndrome are relatively common, whereas overt pulmonary complications of cryoglobulinaemia are rare. Pulmonary haemorrhage is rare in either disorder. The combination of Sjögren's syndrome, cryoglobulinaemia, and acute pulmonary haemorrhage has not been previously reported.

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.

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.

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.

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.

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.

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.