Performing routine follow-up biopsy 1 year after diagnosis does not affect long-term outcomes in coeliac disease.

BACKGROUND: A repeat biopsy is recommended, but often omitted in coeliac disease patients on a gluten-free diet. The effect of performing or not performing repeat biopsies is currently unknown. AIM: To identify factors associated with and the significance of lacking biopsy for long-term outcome. Predictors and the importance of incomplete histological recovery after 1 year was investigated in re-biopsied patients. METHODS: A total of 760 patients participated in a nationwide follow-up study. Medical data were gathered via interviews and patient records, and blood samples were drawn for serology. Current symptoms and well-being were assessed by validated PGWB, SF-36 and GSRS questionnaires. RESULTS: Malabsorption was more common among those with a repeat biopsy (46%) than those without repeat biopsy (33%), P < 0.001, as were severe symptoms at diagnosis (24% vs. 16%, P = 0.05) and concomitant gastrointestinal (40% vs. 32%, P = 0.049) or musculoskeletal (35% vs. 27%, P = 0.023) diseases such as arthritis, osteoporosis and back pain. Repeat biopsy was more rare in subjects diagnosed in private care (11% vs. 23%, P < 0.001) or by screening (10% vs. 16%, P = 0.010). The groups were comparable as to current symptoms and dietary adherence, but those without re-biopsy were less confident of their diet (89% vs. 94%, P = 0.002) and more often seropositive on diet (14% vs. 9%, P = 0.012). They reported better SF-36 physical functioning (P = 0.043) and less pain and indigestion (P = 0.013 and P = 0.046 respectively) and total GSRS (P = 0.052) score. Incomplete mucosal recovery was predicted by more advanced histological (P < 0.001) and serological (P = 0.001) disease at diagnosis, whereas the groups did not differ in long-term adherence, symptoms, seropositivity, questionnaire scores, frequency of fractures or malignancies. CONCLUSIONS: Severe disease at diagnosis predicted the record of a repeat biopsy and incomplete mucosal recovery. Neither lacking biopsy nor incomplete recovery in a relative short time span of 1 year was associated with poorer long-term outcome, although survival bias cannot be excluded.

Gliadin antibodies in older population and neurological and psychiatric disorders.

OBJECTIVES: A variety of neurological and psychiatric disorders have recently been linked to coeliac disease and gluten sensitivity. We here explored whether persistently positive gliadin antibodies (AGA) and coeliac-type HLA increase the risk of gluten sensitivity-related neurological and psychiatric manifestations. The study was carried out in an older population who had consumed gluten for decades but who had no previous coeliac disease diagnosis. MATERIALS AND METHODS: The original study population comprised 4272 randomly selected older individuals, of whom 2089 had AGA and transglutaminase 2 antibodies (antiTG2) measured twice within a 3-year interval. Forty-nine persistently AGA-positive but antiTG2-negative subjects with coeliac-type HLA and 52 randomly selected persistently AGA- and antiTG2-negative age- and sex-matched controls were clinically examined for neurological disorders. The Psychological General Well-Being (PGWB) questionnaire, the SF-36 health survey questionnaire and the Depression Scale (DEPS) were employed to evaluate psychological well-being. The medical files of all the study subjects were analysed for previous illnesses. RESULTS: Persistently AGA-positive but antiTG2-negative older subjects carrying coeliac disease-type HLA did not evince significantly more neurological symptoms or diseases than AGA-negative control subjects (P = 0.682, P = 0.233). There were no statistically significant differences between AGA-positive and AGA-negative groups in psychological well-being and quality of life when measured by PGWB (P = 0.426), SF-36 questionnaires (P = 0.120) and DEPS (P = 0.683). CONCLUSIONS: At population level, persistent AGA positivity did not indicate gluten sensitivity-related neurological and psychiatric disorders.

Altered expression of intestinal human leucocyte antigen D-related and immune signalling molecules in juvenile idiopathic arthritis.

We aimed to study intestinal immune activation status in juvenile idiopathic arthritis (JIA) by assessing intestinal human leucocyte antigen (HLA) class II expression and the mRNA expression levels of the pro- and anti-inflammatory mediators and pattern recognition receptors. HLA-D-related (HLA-DR) expression was assessed using immunohistochemical staining of frozen sections in 11 children with JIA and 17 controls. The gene expression levels of the anti- and proinflammatory cytokines, lymphocyte recognition receptors and pattern recognition receptors were studied with reverse transcription-polymerase chain reaction (RT-PCR) in 14 children with JIA and 12 controls. All subjects had various gastrointestinal (GI) symptoms indicating endoscopic examinations, but eventually were not diagnosed with GI disease. In JIA patients, the expression of HLA-DR was increased in the crypt epithelial cells and in the epithelial basement membrane of the ileum when compared with the controls. Positive HLA-DR staining in the ileal mucosa was associated with the presence of high clinical disease activity of JIA and low mRNA expression of anti-inflammatory mediators, such as forkhead box protein P3 (FoxP3), glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) and transforming growth factor (TGF)-beta. Low ileal expression of interleukin (IL)-10, TGF-ß, FoxP3, Toll-like receptor 2 (TLR-2) and TLR-4 transcripts correlated significantly with a high clinical disease activity in the JIA patients. The increased HLA-DR expression suggests enhanced intestinal antigen presentation in JIA. A correlation between clinical disease activity and low gene expression of tolerogenic mediators in the ileum supports the hypothesis that a link exists between the gut immune system and JIA.

PTFE bypass or thrupass for superficial femoral artery occlusion? A randomised controlled trial.

UNLABELLED: Early results of a thrupass endograft in the treatment of femoral lesions are promising. Less morbidity and better cost-effectiveness are suggested to be achieved in the treatment of chronic lower limb ischaemia with endovascular treatment compared to surgical treatment. PATIENTS AND METHODS: This randomised multicentre trial aimed to enroll a group of 60+60 patients for the treatment of 5-25-cm occlusions of superficial femoral artery (SFA) to be followed up for 3 years. Patients were treated either with endoluminal PTFE thrupass (WL Gore & Ass) or with surgical polytetrafluoroethylene (PTFE) bypass to proximal popliteal artery. Primary patency at 3 years was scheduled to be the primary end-point and secondary patency, functional success, costs and quality of life the secondary end-points. RESULTS: A sample of 100 consecutive SFA occlusions in one of the centres revealed that only 4% of the lesions were amenable for the study. The trial was prematurely terminated due to the results of an interim analysis at the time when 44 patients were recruited: the 1-year primary patency (excluding technical failures) was 48% for thrupass and 95% for bypass (p=0.02). The patency difference in favour of surgical bypass over endovascular thrupass was also sustained after completion of 1-year follow-up, the primary patencies being 46% and 84% at 1 year with grossly equilinear life-table curves thereafter (p=0.18), respectively. The corresponding secondary patencies were 63% and 100% (p=0.05) when excluding technical failures and 58% and 100% (p=0.02) according to intention-to-treat analysis. Secondary outcomes were thus not analysed. CONCLUSION: Treatment of SFA occlusions (TASC IIB and C or Imelda Ia and II) should be done by PTFE bypass rather than by PTFE thrupass, as thrupass is connected with worse early outcome. These results represent only a small category of femoral disease.

Performance of a new rapid whole blood coeliac test in adult patients with low prevalence of endomysial antibodies.

BACKGROUND: In coeliac disease endomysial and transglutaminase autoantibodies are directed against the human autoantigen, transglutaminase. The conventional coeliac antibody tests are performed from serum samples in centralized laboratories. AIMS: To evaluate a rapid and easy immunoglobulin A-class whole blood point-of-care test and its commercial application, the Biocard test, in coeliac autoantibody detection. METHODS: In the whole blood point-of-care test transglutaminase is liberated from the red blood cells by haemolysis. Transglutaminase antibodies, if present, complex with the liberated antigen, and are visualized. Altogether 51 biopsy-proven untreated coeliac adult patients, 48 of the same patients after treatment, and 36 controls were tested. The point-of-care test results were compared with serum endomysial and transglutaminase antibody and Biocard test results and histology. RESULTS: The whole blood point-of-care test was as sensitive (82%) as the serum endomysium test (80%) in detecting untreated coeliac disease while the serum transglutaminase antibody test was superior (88%). The tests had 100% specificity. A positive point-of-care test result seroconverted or the test reaction weakened in 90% of the treated coeliac patients. Biocard test-positive were 22 of the 24 tested untreated coeliac patients. Biocard test-negative were 15 of 19 controls. CONCLUSIONS: The whole blood rapid tests are as reliable as the conventional serological tests in detecting untreated coeliac disease and in coeliac disease diet monitoring.

Increasing prevalence of coeliac disease over time.

BACKGROUND: The number of coeliac disease diagnoses has increased in the recent past and according to screening studies, the total prevalence of the disorder is around 1%. AIM: To establish whether the increased number of coeliac disease cases reflects a true rise in disease frequency. METHODS: The total prevalence of coeliac disease was determined in two population-based samples representing the Finnish adult population in 1978-80 and 2000-01 and comprising 8000 and 8028 individuals, respectively. Both clinically-diagnosed coeliac disease patients and previously unrecognized cases identified by serum endomysial antibodies were taken into account. RESULTS: Only two (clinical prevalence of 0.03%) patients had been diagnosed on clinical grounds in 1978-80, in contrast to 32 (0.52%) in 2000-01. The prevalence of earlier unrecognized cases increased statistically significantly from 1.03% to 1.47% during the same period. This yields a total prevalence of coeliac disease of 1.05% in 1978-80 and 1.99% in 2000-01. CONCLUSIONS: The total prevalence of coeliac disease seems to have doubled in Finland during the last two decades, and the increase cannot be attributed to the better detection rate. The environmental factors responsible for the increasing prevalence of the disorder are issues for further studies.

Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease.

BACKGROUND: Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease. AIM: To investigate whether determination of intestinal transglutaminase 2-targeted autoantibody deposits would detect early developing coeliac disease better than previous methods. METHODS: The study investigated patients previously excluded for coeliac disease: 25 had positive serum coeliac autoantibodies (endomysial), 25 antibody-negative had Marsh I, and 25 antibody-negative had Marsh 0 finding. Seven (median) years after baseline investigation, new coeliac cases were recorded, and small bowel biopsy was offered to the rest of the patients. Serum and intestinal coeliac autoantibodies and intraepithelial lymphocytes were assessed as indicators of developing coeliac disease. RESULTS: Seventeen patients had developed coeliac disease: 13 in the autoantibody-positive group, three in the Marsh I group and one in the Marsh 0 group. At baseline, intestinal coeliac autoantibody deposits had a sensitivity and specificity of 93% and 93% in detecting subsequent coeliac disease, CD3+ 59% and 57%, gammadelta+ 76% and 60%, and villous tip intraepithelial lymphocytes 88% and 71%, respectively. CONCLUSIONS: Endomysial antibodies with normal histology indicates early developing coeliac disease. Transglutaminase 2-targeted intestinal autoantibody deposits proved the best predictor of subsequent coeliac disease.

Self transglutaminase-based rapid coeliac disease antibody detection by a lateral flow method.

BACKGROUND: The conventional coeliac disease antibody tests require patient's sera, and are laborious and time-consuming. AIM: To evaluate a newly developed rapid whole blood test in coeliac disease antibody detection, and its suitability for office use. METHODS: Endogenous tissue transglutaminase found in red blood cells in a whole blood fingertip or venous sample is liberated upon haemolysis and complexes with tissue transglutaminase antibodies, if present. The complexes, captured by a lateral flow system, are visualized within 5 min. Stored samples from 121 untreated, 106 treated coeliac disease patients and 107 controls were evaluated and compared with serum endomysium and tissue transglutaminase antibody tests and histology; 150 patients were prospectively tested on site in the doctor's office. RESULTS: The rapid test showed sensitivity (96.7%) comparable with the serum endomysium and tissue transglutaminase antibody tests from stored samples; specificity was slightly lower (93.5%). When tested on site the results were concordant in 96.7% of cases compared with endomysium and tissue transglutaminase antibody results. The test recognized the disappearance of tissue transglutaminase antibodies on a gluten-free diet. CONCLUSIONS: The self tissue transglutaminase-based rapid test can be easily carried out from a fingertip blood sample on site in the physician's office for both coeliac disease case finding and dietary monitoring purposes.

Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.

BACKGROUND: Some patients with untreated coeliac disease are negative for serum endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). AIMS: To evaluate the clinical and histological features of EmA-negative coeliac disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be seen in the small-bowel mucosa when absent in serum. PATIENTS: Serum EmA was studied in 177 biopsy-proved specimens from adult patients with coeliac disease. 20 patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. METHODS: Clinical manifestations, small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA-negative and EmA-positive patients. RESULTS: 22 patients with IgA-competent coeliac disease were negative for serum EmA. Three of these had small-bowel lymphoma. Patients with EmA-negative coeliac disease were older, had abdominal symptoms more often, and the density of gammadelta+ intraepithelial lymphocytes in their intestinal mucosa was lower than in EmA-positive patients; otherwise the histology was similar. All serum EmA-negative patients with coeliac disease, but none of the disease controls, had gluten-dependent mucosal IgA deposits alongside TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be TG2-specific by its ability to bind recombinant TG2. CONCLUSIONS: Negative serum EmA might be associated with advanced coeliac disease. TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative coeliac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and coeliac disease.

Internal arteriovenous fistula within a radial forearm flap--a novel technique to increase femorodistal bypass graft flow to the diabetic foot and flap covering ischaemic tissue loss.

BACKGROUND: The fascio-cutaneous radial forearm flap is especially suitable to rebuild the contour of the foot, but because of low natural low flow this flap lacks the beneficial effect of large muscle flaps on bypass graft flow. The aim of this study was to introduce a novel technique of flap coverage combined to vascular bypass: an internal av-fistula was created within a radial forearm flap. METHODS: Nine critically ischaemic limbs were treated with a modified radial forearm flap in the Department of Plastic and Vascular Surgery, Helsinki University Central Hospital 1998-2003. All the patients were candidates for a major amputation unless this combined operation was attempted. A two-team approach was used: the vascular surgeon performed the distal bypass and the radial forearm flap was raised by the plastic surgeon. In eight cases a femorodistal bypass was performed and in the ninth the vein graft supplied the flap directly. The internal fistula within the flap was created between the distal end of the radial artery and either the cephalic vein or the concomitant vein of the radial artery. Flow was measured during surgery. RESULTS: Vein graft flow increased significantly after the radial forearm flap anastomosis (76 vs 44 ml/min, p=0.016). The flow of both the bypass graft and the flap artery were higher with the av-fistula patent (p=0.016 and p=0.004). Graft patency was 89% at 2 years. Infection was a major cause of amputation, 1- and 2-year limb salvages being 67 and 53%. CONCLUSION: In a group of diabetic patients increased flow in a vascular bypass graft was achieved by an internal av-fistula within a radial forearm flap. This method is useful in selected cases with poor run off and large ischaemic lesions.

Coeliac disease case finding and diet monitoring by point-of-care testing.

BACKGROUND: Immunoglobulin A class transglutaminase autoantibodies are highly predictive markers of active coeliac disease, a disorder difficult to recognize solely on clinical grounds. AIMS: To develop and evaluate a simple rapid test for point-of-care detection of coeliac autoantibodies. METHODS: The novel whole blood test utilizes the patient's endogenous transglutaminase in red blood cells for detection of transglutaminase-specific immunoglobulin A antibodies present in the blood sample, with normal plasma immunoglobulin A detection as positive test control. We evaluated 284 patients under suspicion of coeliac disease and undergoing jejunal biopsy, and 263 coeliac patients on a gluten-free diet, 383 being tested prospectively in a point-of-care setting. Results were compared with histology, conventional serum autoantibody results and dietary adherence. RESULTS: The rapid test showed 97% sensitivity and 97% specificity for untreated coeliac disease, and identified all immunoglobulin A-deficient samples. Point-of-care testing found new coeliac cases as efficiently as antibody tests in laboratory. Coeliac autoantibodies were detected onsite in 21% of treated patients, while endomysial and transglutaminase antibodies were positive in 20% and 19%, respectively. The positivity rate correlated with dietary lapses and decreased on intensified dietary advice given upon positive point-of-care test results. CONCLUSIONS: Point-of-care testing was accurate in finding new coeliac cases and helped to identify and decrease dietary non-compliance.

The impact of adjuvant av-fistula on cuffed Femorocrural PTFE bypass grafting: flow and pressure response.

OBJECTIVE: The aim of the present study was to assess the effect of an adjuvant av-fistula on prosthetic bypass grafting and whether intraoperative flow measurements could predict patency and adverse events of cuffed femorocrural PTFE bypass with or without an av-fistula. METHODS: A total of 50 patients in need of vascular reconstruction for critical limb ischaemia (CLI) but with no suitable venous conduit were included. RESULTS: The flow values in patients with av-fistula were significantly higher (p=0.009) than in the group without the fistula but the higher flow values did not result in improved patency. The maximum flow velocity (Vmax) in the av-fistula group was significantly higher in the immediate postoperative period (p=0.04), but there was no difference in patency. When a flow value of 50 ml/min was used as a cut-off point, patients with a higher flow had significantly better immediate patency (p=0.025). CONCLUSION: The adjuvant av-fistula neither caused any adverse effects nor had any effect on patency.

In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies.

BACKGROUND: IgA class serum autoantibodies against type 2 (tissue) transglutaminase (TG2) bind to both intestinal and extraintestinal normal tissue sections in vitro, eliciting endomysial, reticulin, and jejunal antibody reactions. It is not known whether similar binding also occurs in coeliac patients in vivo, and may thereby contribute to disease manifestations. AIMS: To investigate intestinal and extraintestinal coeliac tissues for the presence of in vivo bound TG2 specific IgA and its relation to small intestinal mucosal atrophy. PATIENTS: We investigated jejunal samples with normal villous morphology from 10 patients with developing coeliac disease who subsequently progressed to a flat lesion, from 11 patients with dermatitis herpetiformis, and from 12 non-coeliac controls. Six extrajejunal biopsy samples (liver, lymph node, muscle, appendix), obtained based on independent clinical indications from patients with active coeliac disease, were also studied. METHODS: Double colour immunofluorescent studies for in situ IgA, TG2, and laminin were performed. IgA was eluted from tissue sections and tested for TG2 specificity by enzyme linked immunosorbent assay and indirect immunofluorescence. RESULTS: IgA (in one IgA deficient case IgG) deposition on extracellularly located TG2 was detected in jejunal and extrajejunal specimens of all coeliac patients, and also in seven of 11 dermatitis herpetiformis patients, of whom two had no circulating endomysial antibodies. IgA eluted from extraintestinal coeliac tissues was targeted against TG2. CONCLUSIONS: Coeliac IgA targets jejunal TG2 early in disease development even when endomysial antibodies are not present in the circulation. Extraintestinal target sites of coeliac IgA further indicate that humoral immunity may have a pathogenetic role.

Does an adjuvant AV-fistula improve the patency of a femorocrural PTFE bypass with distal vein cuff in critical leg ischaemia?--a prospective randomised multicentre trial.

INTRODUCTION: A lack of suitable veins can cause serious problems when attempting to revascularise critically ischaemic legs. Prosthetic grafts have much worse patency in the femocrural position, despite the use of distal anastomotic cuffs. The use of adjuvant AV-fistula at the distal anastomosis should increase the graft flow above the thrombotic threshold velocity and thus increase prosthetic graft patency. AIM: The aim of the study was to evaluate the benefit of an adjuvant AV-fistula on the patency of a femorocrural PTFE bypass with a distal vein cuff. MATERIALS AND METHODS: This prospective randomised multicentre trial was conducted in four centres. A total of 59 patients with critical leg ischaemia and no suitable veins for grafting were randomised to receive a femocrural PTFE bypass and distal vein cuff, with or without an adjuvant AV-fistula. Thirty-one patients were randomised to the AV-fistula group (AVFG) and 28 to the control group (CG). Six patients were lost to follow-up during the 2-year study time. RESULTS: There were six immediate occlusions in each treatment group, but half of these were saved by re-operation. The mean postoperative ankle-brachial index (ABI) was 0.85 in the AVFG and 0.94 in the CG. The primary and secondary patency rate at 2 years was 29 and 40% for the AVFG and 36 and 40% for the CG (NS). Leg salvage at 2 years was 65 and 68%, respectively (NS). CONCLUSION: Adjuvant AV-fistula does not improve the patency of a femorocrural PTFE bypass with a distal vein cuff.

Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency.

BACKGROUND: IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult. AIMS: To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies. PATIENTS: We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors. METHODS: IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections. RESULTS: The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles. CONCLUSIONS: IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.

Missing endomysial and reticulin binding of coeliac antibodies in transglutaminase 2 knockout tissues.

BACKGROUND: Autoantibodies against transglutaminase 2 (TG2) are thought to be responsible for the endomysial (EMA), reticulin (ARA), and jejunal antibody (JEA) tissue binding of serum samples from coeliac patients but the exclusive role of TG2 in these staining patterns has not yet been established. AIMS: To evaluate whether antigens other than TG2 contribute to EMA/ARA/JEA reactions. PATIENTS: Serum samples from 61 EMA/ARA/JEA positive untreated patients with coeliac disease, 40 dermatitis herpetiformis patients, and 34 EMA/ARA/JEA negative non-coeliac controls were tested. METHODS: TG2 knockout (TG2-/-) and wild-type mouse oesophagus, jejunum, liver, and kidney sections, and TG2-/- sections coated with human recombinant TG2 were used as substrates in single and double immunofluorescent studies for patient IgA binding and tissue localisation of TG2, fibronectin, actin, and calreticulin. RESULTS: None of the patient serum samples elicited EMA, ARA, or JEA binding in TG2-/- morphologically normal tissues. In contrast, 96 of 101 gluten sensitive patient samples (95%) reacted with wild-type mouse tissues and all 101 reacted in EMA/ARA/JEA patterns with TG2-/- mouse tissues coated with human TG2. Serum IgA binding to TG2-/- smooth muscle cells was observed in low titres in 31.1%, 27.5%, and 20.5%, and to TG2-/- epithelium in 26.3%, 5.0%, and 8.8% of coeliac, dermatitis herpetiformis, and control samples, respectively. These positivities partly colocalised with actin and calreticulin but not with TG2 or fibronectin. CONCLUSIONS: EMA/ARA/JEA antibody binding patterns are exclusively TG2 dependent both in coeliac and dermatitis herpetiformis patients. Actin antibodies are responsible for some positivities which are not part of the EMA/ARA/JEA reactions.

Coeliac disease among healthy members of multiple case coeliac disease families.

BACKGROUND: The main objective of the study was to assess the frequency of undetected coeliac disease among the first-degree relatives of families with two or more previously diagnosed coeliac disease patients. The value of the serum endomysial antibody test as a single means of detecting clinically silent coeliac disease was evaluated. The correlation of endomysial and tissue transglutaminase antibodies and the correlation of endomysial antibodies to the HLA typical for coeliac disease was determined. METHODS: A total of 137 multiple-case coeliac disease families with 872 family members were recruited; 466 healthy family members were simultaneously screened for gliadin and endomysial antibodies and thereafter for tissue tranglutaminase antibodies. Antibody-positive persons were typed for HLA-DQ2 and DQ8. The diagnosis of coeliac disease was based on the typical mucosal lesion on small-bowel biopsies. RESULTS: Forty-four (9.4%) of the healthy family members were positive for endomysial and 48 (10.3%) for gliadin antibodies; 42 biopsies revealed 29 new coeliac disease patients (6.2% of healthy individuals). Endomysial antibodies detected 97% and gliadin antibodies 52% of the new cases. All 44 endomysial-antibody-positive and 35 of 48 gliadin-antibody-positive individuals were positive for DQ2. Tissue transglutaminase antibodies corresponded well with endomysial antibodies. CONCLUSIONS: Undetected coeliac disease is common even among healthy first-degree relatives of multiple case families. The findings emphasize the value of serum endomysial antibodies in the detection of clinically silent coeliac disease. Endomysial-antibody-positive individuals, unlike gliadin-antibody-positive ones, share the coeliac disease-type HLA-DQ.

Cow's milk protein-sensitive enteropathy at school age.

OBJECTIVES: Cow's milk protein-sensitive enteropathy (CMSE) may persist in children to school age. We sought to define the morphologic and immunohistochemical features of persistent CMSE. STUDY DESIGN: We studied 15 children with a definite diagnosis of CMSE on the basis of a blind challenge, 12 children with suspected cases of CMSE, 11 children with celiac disease, and 12 control children. RESULTS: Typical findings in children with CMSE were endoscopically visible lymphonodular hyperplasia of the duodenal bulb and lymphoid follicles without villous atrophy in biopsy samples. The patients with definite CMSE showed significantly increased densities of intraepithelial T cells skewed clearly to gammadelta(+) cells, compared with the control patients but fewer than in the patients with celiac disease. The study children showed no aberrant upregulation of HLA-DR expression in the duodenal mucosa, and the prevalence of HLA DQ2 antigen among them was equal to that in the control children. CONCLUSIONS: Our observations corroborated the claim that CMSE at school age is an identifiable clinical entity. Immunohistochemical findings suggest the abrogation of antigen tolerance locally on the gastrointestinal mucosa. A careful clinical assessment that includes a long elimination-challenge test supported by typical endoscopic and histologic findings form the basis for diagnosis.

Reference intervals for the markers of proteinuria with a standardised bed-rest collection of urine.

Reference intervals for markers of proteinuria or glomerular charge selectivity were measured in 61 healthy female and 61 healthy male individuals. Timed bed-rest and daytime collections were used to assess significance of preanalytical variability of results. Bed-rest collections are advisable for research on renal damage, whereas in routine care, robust protein/creatinine ratios work as practical estimates of protein excretion rates, the correlations to excretion rates improving with increasing proteinuria. For glomerular charge selectivity, pancreatic/salivary isoamylase clearance ratio showed lower within-subject biological variation than IgG/IgG4 clearance ratio, allowing more accurate classification into normal and reduced charge selectivity. With our method, the lower 2.5% reference intervals for isoamylase clearance ratio were 1.1 in men and 1.9 in women.