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M Mäki

Publications and source records attributed to M Mäki.

At least 91 records · Page 5Linked to original sources
PubMed1999

Increased density of jejunal gammadelta+ T cells in patients having normal mucosa--marker of operative autoimmune mechanisms?

Both from a clinical and a biological point of view, coeliac disease can be classified among the autoimmune diseases, or one could suspect autoimmune mechanisms to be operative in the disease. The aim of the present study was to find evidence for mucosal markers of coeliac disease latency in patients clinically suspected but on routine biopsy excluded for the disease. Monoclonal antibodies were used to stain jejunal intraepithelial lymphocytes and mucosal HLA-DR. Serum IgA-class reticulin autoantibodies were measured by an indirect immunofluorescence and gliadin antibodies by an enzyme-linked immunosorbent assay method. The DQA1*0501 and DQB1*0201 alleles were determined. Twenty-seven of 107 consecutive patients had coeliac disease. Altogether 39 of 79 (49%) children with normal jejunal mucosa had an increased density of intraepithelial gammadelta+ T cells (> or = 4.4 cells/mm). IgA-class reticulin autoantibodies were positive in 18 (23%) of the children excluded for coeliac disease. The antibody positivity was mostly seen in patients carrying the DQAI 0501 and DQB1*0201 alleles. Also, reticulin autoantibody-positive children having normal jejunal mucosal morphology had significantly higher densities of intraepithelial gammadelta+ T cells than antibody negative ones. On 1.5-4.5 year follow-up four out of 18 (22%) children primarily excluded for coeliac disease showed mucosal deterioration and coeliac disease. Many patients clinically suspected of coeliac disease but having normal jejunal mucosa show markers of coeliac disease latency which may be gluten-induced indicating autoimmune mechanisms to be operative in the gut.

Adolescent↗
PubMed1998

Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease.

BACKGROUND & AIMS: Tissue transglutaminase has been reported to be the target for endomysial antibodies in celiac disease. We sought to establish whether immunoglobulin (Ig) A class tissue transglutaminase autoantibodies can be considered specific for celiac disease. METHODS: Serum samples from 136 patients with untreated celiac disease (diagnosed according to the criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition) and 207 disease controls were studied. Enzyme-linked immunosorbent assay (ELISA) and Western blots were performed using calcium-treated and untreated tissue transglutaminase as antigen. Reticulin, endomysial, and mouse monoclonal tissue transglutaminase antibodies were studied by an indirect immunofluorescence method and gliadin antibodies with ELISA. RESULTS: The calcium-activated tissue transglutaminase autoantibody ELISA was highly sensitive (129 of 136) and specific (194 of 207) in detecting celiac disease. The new autoantibody ELISA test correlated well with the endomysial antibody test. Tissue transglutaminase autoantibody ELISA showed a clearly better predictive potential than the IgA class gliadin antibody ELISA. Immunoblots and ELISA blocking studies showed that calcium is needed for the specific antigen-antibody reaction to occur. Double immunofluorescence staining in human umbilical cord with sera from patients with celiac disease and with monoclonal tissue transglutaminase antibodies showed complete overlap. CONCLUSIONS: Calcium-activated tissue transglutaminase autoantibody ELISA is highly accurate in detecting untreated celiac disease. Tissue transglutaminase seems to be the target self-antigen for endomysial antibodies.

Adolescent↗
PubMed1998

HLA-DQ2-negative celiac disease in Finland and Spain.

Genetic susceptibility to celiac disease (CD) is strongly associated with DQA1*0501 and DQB1*02 (= DQ2). To study whether CD patients without DQ2 share other MHC class II or TNF alleles, we screened DQ2-negative patients in Finland and Spain. Twelve of 84 (14%) Finnish patients and 13 of 189 (6%) Spanish patients were negative for DQ2. We observed that all but two of altogether 25 DQ2-negative patients had the DR4 DQ8 haplotype, or either DQA1*0501 or DQB1*02 alone. Also, all but three were positive for DRB4*01. The only patients without any of these alleles were both positive for DR 13. There was a clear difference between Finland and Spain: Ten (83%) of the 12 Finnish DQ2-negative patients but only five (38%) of the 13 Spanish patients had DRB1*03, DQA1*03, DQB1*0302 (= DQ8) alleles. Of the Spanish patients, eight (62%) had DQB1*02 without DQA1*0501 and three (23%) had DQA1*0501 without DQB1*02. None of the TNF, TAP, or DPB1 alleles was found to be significantly associated with CD. Our results indicate that in addition to the DQ2 heterodimer, the other major risk alleles for CD are DR4 DQ8, and either DQA1*0501 or DQB1*02 alone. Patients without these alleles appear to be very rare, only two (0.7%) were identified in altogether 253 patients tested.

Adolescent↗
PubMed1998

Oral mucosal changes in coeliac patients on a gluten-free diet.

Oral mucosal lesions or dental enamel defects may be the only presenting features of coeliac disease. A series of 128 patients with coeliac disease (CD) on a gluten-free diet (GFD), 8 patients with a newly diagnosed CD, and 30 healthy controls participated in a clinical and histopathological study of their oral mucosa. Oral mucosal lesions occurred in 71/128 GFD-treated CD patients. in 4/8 untreated and in 10/30 controls, and oral symptoms in 85/128, in 6/8 and in 10/30, respectively. Five CD patients had aphthous ulcers. Moderate to severe lymphocytic inflammation occurred in 36/117 and in 14/117 of the biopsy specimens of GFD-treated CD patients, in 1/8 and 2/8 of untreated CD patients, and in 3/30 and in 1/30 of controls, respectively. Intraepithelial T-cells were significantly more frequent in GFD-treated CD patients than in controls. There was no difference between untreated CD patients and controls. In the lamina propria of the GFD-treated CD patients, T-cells were more frequent than in the other groups. Mast cells were significantly more frequent in patients with GFD-treated CD. Nine GFD-treated CD patients had raised serum endomysium IgA antibody titres, although five of them reported to follow a strict GFD. A lack of strict compliance with a GFD may be related to the high prevalence of oral changes and symptoms. In addition, T-cell infiltration in the oral mucosa tends to increase with a longer duration of CD, independent of GFD-treatment. Clinically, it is important to study the oral cavity of patients suspected of having CD where the only clue to the disease may reside, since no less than 66% of the patients in this study had oral symptoms.

Adolescent↗
PubMed1998

Circulating T lymphocyte subsets in coeliac disease (CoD) patients and healthy family members.

Increased proportions of circulating antigen-primed CD45RO+ TCR gammadelta cells have been found in untreated CoD patients. As certain immunological features are now found in both CoD and healthy persons carrying the HLA DQ2 heterodimer, we sought to establish whether healthy members of the families of CoD patients who are positive for HLA DQ2 and also have increased densities of TCR gammadelta intraepithelial lymphocytes (IEL) in their small bowel mucosa have elevated levels of circulating TCR gammadelta memory cells. Peripheral blood T cells were analysed by flow cytometry in 22 patients with CoD and 16 healthy family members. Untreated CoD patients had higher percentages of circulating CD45RO+ TCR gammadelta cells and CD45RO+ Vdelta1+ cells than healthy family members. On the other hand, the amount of circulating Vdelta1+ lymphocytes was lower in patients with CoD compared with healthy family members. In contrast, no differences were found between HLA DQ2+ and HLA DQ2- healthy family members in respect of circulating TCR gammadelta cell subsets. The change in circulating TCR gammadelta cell subsets found in patients with CoD is thus a consequence of an ongoing immunological process which diminishes on a gluten-free diet rather than a phenomenon directly caused by DQ2. These changes in peripheral blood are not found in healthy individuals who have the same HLA alleles DQA1*0501 and DQB1*0201 encoding the HLA DQ2 and who also have increased densities of TCR gammadelta IEL in their otherwise normal jejunal mucosa.

Adolescent↗
PubMed1998

IgA- and IgG-class antihuman umbilical cord antibody tests in adult coeliac disease.

BACKGROUND: An antiendomysium antibody test using human umbilical cord as antigen has recently been introduced. METHODS: We determined IgA- and IgG-class antihuman umbilical cord (HUC-ab), antireticulin (ARA), and antigliadin antibodies (AGA) in 92 untreated adult coeliac patients, in 95 non-coeliac subjects, and in 4 coeliac patients with selective IgA deficiency. Tissue antibodies were measured with an indirect immunofluorescence method and AGA with an enzyme-linked immunosorbent assay. RESULTS: Of adult coeliac patients 85% were positive for IgA-class HUC-ab, 78% were positive for ARA, and 80% for AGA; the specificity for HUC-ab and ARA was 100%, and for AGA 86%. Combination of HUC-ab, ARA, and high-titre AGA increased the sensitivity to 96% without loss of specificity. IgG-class HUC-ab was positive in 12% of coeliac patients, in all four coeliac patients with IgA deficiency, and in none of the controls. CONCLUSIONS: The HUC-ab test is highly specific but not 100% sensitive for detecting adult coeliac disease. A combination of the IgA-class HUC-ab, ARA, and high-titre AGA tests is recommended. In selective IgA deficiency the IgG-class HUC-ab test seems to work well.

Adult↗
PubMed1998

Small-bowel mucosal inflammation in reticulin or gliadin antibody-positive patients without villous atrophy.

BACKGROUND: We investigated whether individuals with positive coeliac disease antibodies but without small-bowel villous atrophy have mucosal inflammation implicating gluten-sensitivity. METHODS: Small-bowel mucosal morphology; CD3+, alphabeta+, and gammadelta+ T-cell receptor-bearing intraepithelial lymphocytes; and mucosal HLA-DR expression were studied in 96 IgA-class antireticulin or antigliadin antibody-positive adults suspected of having coeliac disease and in 27 control subjects. RESULTS: Villous atrophy compatible with coeliac disease was found in altogether 29 patients, in 18 of 21 (86%) patients with both antireticulin and antigliadin antibodies, in 9 of 15 (60%) patients with antireticulin antibodies only, and in 2 of 60 (3%) with antigliadin antibodies only. In 67 antibody-positive patients with normal villous architecture the densities of CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes were significantly higher than in non-coeliac control subjects. Ten patients with initially increased densities of gammadelta+ T cells but normal villous structure underwent a follow-up biopsy after 4-18 months, which showed villous atrophy in five patients. CONCLUSIONS: IgA-class antireticulin or antigliadin antibody-positive patients with normal small-bowel mucosal morphology frequently have immunohistochemical markers of coeliac disease latency. Together with our follow-up data this implies that they may be gluten-sensitive.

Adolescent↗
PubMed1998

Celiac sprue in patients with chronic oral mucosal symptoms.

Eighty-two consecutive patients with oral mucosal disorders were screened for celiac sprue with serum immunoglobulin A (IgA)-class endomysial and gliadin antibodies. In positive cases the diagnosis of celiac sprue was established by duodenal biopsy. Four patients were positive for endomysial antibodies and 22 for gliadin antibodies. Four (4.9%) patients were found to have celiac sprue: three of them by screening and one was previously diagnosed. Endomysial antibodies were present in all three newly diagnosed patients with celiac sprue, and gliadin antibodies were present in one. Sixteen of 22 patients positive for gliadin antibodies underwent small bowel biopsy, and 15 had normal mucosa. Patients with chronic oral mucosal disorders and a positive endomysial antibody test may suffer from celiac sprue. By contrast, gliadin antibodies were very prevalent even in the absence of celiac sprue.

Adolescent↗
PubMed1998

Autoantibodies in celiac disease: importance of fibroblasts.

BACKGROUND: Serum reticulin and endomysium autoantibodies are highly celiac disease-specific, and the autoantigens have been shown to be derived from human fibroblasts. Among human tissues, the umbilical cord also expresses these antigens. This study was conducted to compare different autoantibody tests and especially to elucidate whether human umbilical cord is a suitable substrate in tests and whether the cord jelly-derived fibroblasts express the antigens. METHODS: The indirect immunofluorescence method was used to detect the tissue and Wharton's jelly-derived fibroblast antibodies in 334 celiac disease and control sera samples. Affinity chromatography studies were used to show the correlation between human fibroblast-derived autoantigens and tissue and gliadin antibodies. The jelly-derived fibroblasts were used as antigen in a whole-cell enzyme-linked immunosorbent assay. RESULTS: Celiac disease patient sera showed IgA-class human umbilical cord antibody with high sensitivity (100%) and specificity (99%). All celiac disease patient sera tested showed in indirect immunofluorescence the molecules expressed by Wharton's jelly-derived fibroblasts. The whole-cell fibroblast autoantibody enzyme-linked immunosorbent assay had a sensitivity of 100% and a specificity of 81%. Human fibroblast-derived celiac disease autoantigens absorbed most of the IgA responsible for human umbilical cord antibodies but not the IgA responsible for gliadin antibodies in the same sera. CONCLUSIONS: Wharton's jelly-derived fibroblast autoantibodies tested in a novel whole-cell enzyme-linked immunosorbent assay correlated well with the human umbilical cord but not with gliadin antibodies.

Adolescent↗
PubMed1998

TNF microsatellite alleles a2 and b3 are not primarily associated with celiac disease in the Finnish population.

Recently, an independent association between tumor necrosis factor (TNF) gene polymorphism and celiac disease was observed in the Irish population. We tested this association in Finnish patients with celiac disease. The TNF microsatellite alleles a2 and b3 were strongly associated (Pcorr<0.0001 for both) with celiac disease when the patients were compared to the random population. However, when the comparison was made with the DQ2-matched controls, no association could be found. We therefore conclude that in Finland the TNFa2 and b3 alleles are associated with DQ2-positive haplotypes rather than celiac disease.

Alleles↗
PubMed1998

Tolerance to oats in dermatitis herpetiformis.

OBJECTIVES: Recent studies on coeliac disease have shown that oats can be included in a gluten-free diet without adverse effects on the small bowel. The presence of a rash is also a sensitive indicator of gluten ingestion in dermatitis herpetiformis, and this was used to study whether patients with this disease could also tolerate oats. PATIENTS/METHODS: Eleven patients with dermatitis herpetiformis in remission on a gluten-free diet were challenged daily with 50 g oats for six months. Clinical symptoms were recorded, serum samples taken, and skin and small bowel biopsies performed before and after the oat challenge. A control group comprised of 11 patients with dermatitis herpetiformis on a conventional gluten-free diet was also studied. RESULTS: Eight patients challenged with oats remained asymptomatic, two developed a transient rash, and one withdrew because of the appearance of a more persistent but mild rash. Three of the 11 controls also developed a transient rash. IgA endomysial antibodies remained negative in all patients. The small bowel villous architecture, the densities of intraepithelial CD3 and alpha/beta and gamma/delta T cell receptor positive lymphocytes and crypt epithelial cell DR expression remained unaltered during the oat challenge. CONCLUSIONS: The results confirm the absence of oat toxicity on the gluten sensitive small bowel mucosa and suggest that the rash in patients with dermatitis herpetiformis is not activated by eating oats.

Adult↗
PubMed1997

Coeliac disease.

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Celiac Disease↗
PubMed1997

Density of gamma/delta+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age.

Increased density of gamma/delta T cell receptor (TCR)+ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial gamma/delta and alpha/beta TCR+ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial gamma/delta T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of gamma/delta+ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P < 0.0001). In controls, the density of gamma/delta+ cells remained low throughout the age-range studies, from age 0.6-57 years. In controls, alpha/beta+ cells increased with age (r = 0.57, P < 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation.

Adolescent↗
PubMed1997

Human fibroblast-derived molecules as antigens in enzyme-linked immunosorbent assay for coeliac disease-specific IgA.

We have recently shown that cultured human fibroblasts synthesize and secrete protein molecules that bind to IgA-class anti-reticulin and anti-endomysium antibodies but not to anti-gliadin antibodies in coeliac disease patient sera. In the present report, we describe a reproducible method for purification of these antigen molecules from fibroblast culture medium. Using reversed-phase chromatography as the final purification step, four different protein molecules reacting with coeliac disease patient sera IgA were obtained. In enzyme-linked immunosorbent assay (ELISA) for coeliac disease-specific IgA, a mixture of 0.5 microgram of the four reversed-phase-separated molecules was used as antigen. The optical density values in ELISA of the sera from newly diagnosed coeliac disease patients (n = 34) were 0.740-3.400 (mean 1.830) and in control patients (n = 66) 0.090-0.850 (mean 0.320). Using an arbitrary cut-off level of 0.700, the sensitivity of the present autoantibody test was 100%, specificity 91% and positive predictive value 85%. Our identified autoantigens may generate the production of the classical tissue antibodies, known as anti-reticulin and anti-endomysium antibodies, and may be used as antigen in an immunoassay for the antibodies.

Adolescent↗
PubMed1997

A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients.

OBJECTIVE: To assess endoscopically the effect of prophylactic short-term ranitidine treatment in the prevention of stress-induced gastric lesions in neonatal intensive care unit (ICU) patients. DESIGN: Prospective, randomized study. SETTING: Department of Neonatal Intensive Care, University Hospital of Tampere. PATIENTS: Fifty-three infants were enrolled in a randomized, controlled study. Forty-eight (90%) of these patients underwent endoscopic examination and were evaluated. INTERVENTIONS: A histamine-2-receptor blocker, ranitidine, was given prophylactically after birth for 4 days to infants mechanically ventilated and treated in the neonatal ICU. The gastric mucosa was both visually and histologically evaluated after 3 to 6 days, and the outcome of the infants was registered. MEASUREMENTS AND MAIN RESULTS: In the 23 infants prophylactically treated with ranitidine, the gastric mucosa was visually classified as normal in 14 (61%) infants as compared with five (20%) of 25 controls (p < .004). Histologic lesions showed parallel results (57% vs. 16%, p < .004). Eight gastric ulcers were diagnosed endoscopically in the control group vs. none in the treatment group. The ulcers were all clinically "silent" at the time of endoscopy. According to logistic regression modeling, the decreased risk for gastric mucosal lesions in infants receiving prophylactic ranitidine was 0.03 (95% confidence interval 0.003 to 0.178). Surfactant treatment for infant respiratory distress syndrome also decreased the risk for stress-induced gastric mucosal lesions (odds ratio 0.083; 95% confidence interval 0.009 to 0.788), whereas other variables (birth weight, gestational age, Apgar scores, cord blood pH, and duration of intubation) had no significant effect. No side effects could be attributed to the ranitidine treatment. CONCLUSION: We conclude that short-term prophylactic ranitidine treatment prevents gastric mucosal lesions in newborn infants under stress.

Birth Weight↗
PubMed1997

Canine major histocompatibility complex genes DQA and DQB in Irish setter dogs.

Information about genetic variation within the canine major histocompatibility complex (MHC) class II genes is limited. In common with most other vertebrate species the canine MHC, or DLA, includes genes which are homologous to human DR, DQ, and DP. Recently, at least one functional DLA DQ gene-pair has been characterized, but so far systematic screening efforts have been lacking. In the present study, we sequenced both cDNA and genomic clones derived from DLA DQ genes of Irish setter dogs. This breed was of interest, since it shows a high prevalence of gluten sensitive enteropathy (GSE), which may be a useful animal model for celiac disease (CD) of man. Interestingly, few of the alleles found in Irish setters were identical to those previously detected in other breeds. Three novel DLA DQA and four novel DLA DQB alleles were discovered in 19 unrelated dogs. Strong association between certain HLA DQ alleles and CD of man prompted us to screen the DQ alleles of members of a family of gluten-sensitive Irish setter dogs. No haplotypes or alleles were shared by all affected dogs, but one frequent haplotype in this family was also detected in an unrelated gluten-sensitive Irish setter; this haplotype was absent in the healthy dogs. This observation warrants further investigation by screening the DQ alleles of a large population of unrelated gluten-sensitive Irish setters.

Alleles↗
PubMed1997

Intraepithelial lymphocytes bearing the gamma/delta receptor in the oral and jejunal mucosa in patients with dermatitis herpetiformis.

Lymphocytes bearing T cell receptor (TcR) gamma/delta are increased in the jejunal mucosa of patients with dermatitis herpetiformis (DH) and coeliac disease. In this study, we examined whether increased numbers of gamma/delta TcR positive lymphocytes occur in the oral mucosa of patients with DH. Oral and jejunal mucosal biopsies were taken from 13 newly diagnosed and 13 gluten free diet (GFD)-treated patients with DH. Monoclonal antibodies and avidin-biotin peroxidase method was used for staining, and TcR positive cells were counted from the buccal and jejunal epithelium. Very few gamma/delta TcR positive lymphocytes were seen in the buccal epithelium of untreated or GFD-treated DH patients (median 0.4 and 0.3 cells/mm2), whereas alpha/beta TcR positive lymphocytes were frequent in both groups of DH patients (154 and 250 cells/mm2) and healthy controls (135 cells/mm2). The numbers of gamma/delta TcR positive intraepithelial lymphocytes were significantly increased in the jejunum of both untreated (43 cells/mm) and GFD-treated (27 cells/mm) DH patients compared to control patients (2.2 cells/mm). The present study did not, therefore, disclose any evidence for active recruitment of gamma/delta TcR positive lymphocytes in the oral epithelium, but showed substantial amounts of intraepithelial alpha/beta TcR positive lymphocytes both in DH patients and healthy controls.

Adult↗