IgA-antigliadin antibodies in patients with IgA nephropathy: the secondary phenomenon?

Circulating IgA-antigliadin antibodies (IgA-AGA) are often found in patients with IgA nephropathy (NP). IgA-AGA are sensitive markers of an abnormal immune system reaction to gluten, seen particularly in patients with celiac disease. However, a lack of IgA-antireticulin and IgA-antiendomysium antibodies and often jejunal mucosal atrophy of patients with IgA NP suggest that most patients do not have latent celiac disease. To examine the relationship between IgA-AGA and clinical data, enzyme-linked immunosorbent assays for IgA-AGA were performed in 28 patients with IgA NP and in 50 healthy persons. The results were calculated in arbitrary units (AU). The cutoff level for a negative or a positive test was found to be 60 AU, calculated according to the AGA test result (mean + 3 SD) in 50 healthy persons. The following clinical data were assessed: age, gender, disease duration, daily proteinuria, blood pressure, serum creatinine, and creatinine clearance. Control sera were negative for IgA-AGA. Positive IgA-AGA tests were observed in 14 of the 28 patients (p < 0.0001 vs. controls) and high levels of IgA-AGA (AU >90) in 6 of the 28 patients (p < 0.001 vs. controls). The mean duration of the disease of the patients with positive IgA-AGA was significantly longer as compared with the patients who had a negative antibody test. IgA-AGA correlated with age (p < 0.05, r = 0. 56), disease duration (p < 0.05, r = 0.40), and blood pressure (p < 0.05, r = 0.48). Antireticulin and antiendomysium antibody tests were negative in all patient and control sera. We conclude that IgA-AGA are associated with the progression of IgA NP. Our findings support the current concept about the pathogenesis of IgA NP, where the defective IgA production itself may be the primary and intestinal lesions as well as the production of IgA-AGA the secondary phenomenon.

The epidemiology of primary biliary cirrhosis: immunological problems.

Primary biliary cirrhosis (PBC) has received considerable attention as an autoimmune disease, where in addition to immunological mechanisms, environmental factors may have an important role. Therefore the epidemiological analysis of disease prevalence and progression in association with immunological studies has been one of the hot areas of PBC research during recent years. In this paper the epidemiological data on PBC and its immunological marker--anti-mitochondrial antibodies--have been presented from a comparative viewpoint.

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role.

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.

Aminoterminal propeptide of type III procollagen and hyaluronan in patients with primary biliary cirrhosis: markers of fibrosis in primary biliary cirrhosis.

The aminoterminal propeptide of type III procollagen (PIIINP) and hyaluronan have previously been studied in different liver diseases. The results of these studies are controversial. The aim of the present study was to examine the relationship between PIIINP and hyaluronan levels and the clinical, biochemical and histological features of primary biliary cirrhosis (PBC) and its prognosis. Fifty-five PBC patients were studied at the time of diagnosis of PBC and were followed up for a mean of 58 months. During the follow-up period 21 patients died. In addition, 30 healthy subjects were examined in the present study. Hyaluronan and PIIINP were measured by radioimmunoassay and the levels of both PIIINP and hyaluronan were higher in PBC patients than in healthy volunteers (P < 1.8 x 10(-6) and 1.6 x 10(-9), respectively). Hyaluronan and PIIINP levels were above normal values in 82 and 84% of PBC patients, respectively. There were correlations between PIIINP and hyaluronan and the histological stage of PBC (r = 0.44, P < 0.004 and r = 0.56, P < 0.00001, respectively). The correlation between PIIINP and hyaluronan was 0.46 (P < 0.0035). In symptomatic patients, both PIIINP and hyaluronan values were higher than in controls (P < 0.002 and P < 0.006, respectively). The levels of PIIINP correlated significantly with bilirubin (r = 0.43, P < 0.006), while hyaluronan was correlated with age (r = 0.33, P < 0.015), pruritus (r = 0.32, P < 0.02), fatigue (r = 0.41, P < 0.003), hepatomegaly (r = -0.46, P < 0.0008), the presence of oesophageal varices (r = 0.34, P < 0.002), weight loss (r = 0.29, P < 0.05), bilirubin (r = 0.54, P < 0.0001), albumin (r = -0.30, P < 0.04), extent of fat excretion (r = 0.53, P < 0.009) and length of symptomatic period before diagnosis of PBC (r = 0.43, P < 0.002). Using Cox's logistic regression analysis, survival was found to be influenced by bilirubin concentration but not by hyaluronan, PIIINP, age, albumin or histological stage. Therefore, hyaluronan is a more sensitive marker for predicting advanced PBC than is PIIINP. However, neither hyaluronan nor PIIINP gave any indication of prognostic outcome.

Clinical significance of different antinuclear antibodies patterns in the course of primary biliary cirrhosis.

BACKGROUND/AIMS: The significance of antinuclear antibodies (ANA) in primary biliary cirrhosis (PBC) patient is still controversial in the literature. The purpose of this paper is to investigate the clinical significance of ANA in PBC patients. MATERIALS AND METHODS: Sixty-nine patients with PBC were investigated. Control groups included 21 patients with autoimmune hepatitis, 26 patients with alcoholic liver disease, 13 patients with systemic connective tissue disease and 27 healthy persons. ANA was detected by an immunofluorescence method on rat liver tissue sections and HEp-2 cells at serum dilution 1/40. RESULTS: In 48 out of 69 PBC patients (70%), ANA was positive in HEp-2 cell line, but in rat liver tissue sections only 29% of patients had positive ANA reactions. Most frequent patterns were multiple nuclear dots (MND) in 42% and perinuclear in 16%. MND-ANA was also found in two autoimmune hepatitis patients and in one systemic lupus erythematosus patient. Survival from the moment of developing first symptom(s) attributable to liver disease was longer in the ANA positive patients than ANA negative ones (p < 0.02). Despite immunosuppressive treatment, in most of ANA positive patients (73%) ANA did not disappear. Most frequent ANA patterns in autoimmune hepatitis and systemic connective tissue diseases patients were homogeneous and anticentromere, respectively. CONCLUSIONS: Immunofluorescence method on HEp-2 cell line for ANA detection is more sensitive than on rat liver tissue sections. In PBC patient's incidence of ANA, especially MND-ANA is a frequent immunological abnormality. ANA positive patients have better prognosis for survival.

Primary biliary cirrhosis in Estonia. With special reference to incidence, prevalence, clinical features, and outcome.

BACKGROUND: Primary biliary cirrhosis (PBC) is a liver disease of unknown etiology, whose occurrence varies greatly between different regions. For a long time there have been no published data about the incidence and prevalence of PBC from Eastern Europe countries. METHODS: The incidence and prevalence of PBC have been investigated in the Estonian population during the period 1973-92. Two sources of information were used: an information circular/questionnaire was sent to all district hospitals and gastroenterologists, and the case histories of all patients with a positive antimitochondrial antibody titer of 1:40 or more were reexamined. RESULTS: During this period 69 cases of PBC were diagnosed. The male to female ratio was 1:22; 13% of the patients were asymptomatic. The mean annual incidence was 2.27 per million, and on 31 December 1992 the point prevalence was 26.9 per million. There were differences in prevalence among the various districts of Estonia. Associated autoimmune conditions were reported in 32% of the patients. Mean survival from the time of diagnosis was 52.5 months. CONCLUSIONS: The incidence of PBC in Estonia is at the lower end of the range reported in the world literature. This has probably partly been caused by a low percentage of asymptomatic and male patients.

Risk of recurrence of gastric ulcer, chronic gastritis, and grade of Helicobacter pylori colonization. A long-term follow-up study of 25 patients.

BACKGROUND: We describe here our observations on colonization of the gastric mucosa by Helicobacter pylori in a long-term follow-up of 25 patients with gastric ulcer (GU). METHODS: All patients were followed-up endoscopically for more than 10 years (mean, 16 years) and endoscopically verified to have GU in the angular or corpus area of the stomach. None had received treatment with H2 blockers or omeprazole or had undergone any maintenance therapy or surgery. On the basis of the endoscopic findings on the activity of GU at follow-up endoscopies, the patients were divided into a group of subjects with 'low risk' of recurrence (15 patients who either had no (7 patients) or only a single recurrence (8 patients) at the first follow-up endoscopy but not thereafter) and into those with a 'high risk' of recurrence (10 patients who had at least 2 episodes of recurrence at follow-up endoscopies). RESULTS: A severe bilateral (antrum and corpus) colonization of the gastric mucosa by H. pylori at the first re-examination (1-6 years after the initial diagnosis of GU) was the most important characteristic feature in the patients with high risk of recurrence as compared with those with low risk. In the course of the follow-up, colonization of the corpus mucosa by H. pylori remained rather unchanged in both high- and low-risk subjects but decreased in grade in antrum particularly in those with low risk (no bacteria at the last endoscopy in 13 of 16 low-risk patients and in 2 of 8 high-risk patients). In both low- and high-risk groups corpus gastritis developed progressively into atrophic gastritis (11 of 25 patients had severe corpus atrophy at the last endoscopy). On the other hand, antral gastritis showed a tendency to heal (13 of 24 patients had normal or only slightly gastric antrum at the last endoscopy). CONCLUSIONS: The observations indicate that the H. pylori plays a role in and associates closely with the long-term course of angular or corpus GU disease and is related to the tendency of these ulcers to recur.

Enzyme-linked immunosorbent assays for the determination of IgG, IgA, and IgM autoantibodies to pyruvate dehydrogenase in primary biliary cirrhosis.

Autoantibodies to the recently described mitochondrial autoantigen, pyruvate dehydrogenase, have been shown to be specific for primary biliary cirrhosis. In the present study we describe enzyme-linked immunosorbent assays to detect antibodies of IgG, IgA, and IgM classes reactive with pyruvate dehydrogenase. These assays showed high sensitivity (95%) and specificity (100%) for primary biliary cirrhosis when evaluated in 28 patients with primary biliary cirrhosis, 59 disease controls, and 214 healthy persons. Quantitation of these autoantibodies by calculating the areas under the sera titration curves of 10 primary biliary cirrhosis patients indicated that an increase in IgA antibodies to pyruvate dehydrogenase is related to more rapid disease progression.

Autoimmune reactions to gastric mucosa in chronic gastritis: a review.

The main results of two-decade co-operation between Tartu University, Estonia, and the University of Helsinki, Oulu and Tampere in Finland on immunology of chronic gastritis are presented. These results include data on cell-mediated and humoral immunity to autoantigens from gastric antrum and corpus mucosa in chronic gastritis, gastric ulcer, gastric carcinoma and other gastric diseases, as well as in random samples from two populations.

Grade of Helicobacter pylori colonisation, chronic gastritis and relative risks of contracting high gastric ulcers: a seven-year follow-up.

A series of 38 patients with high gastric ulcer (GU) was examined twice a seven-year interval. One-third of the patients had an active ulcer at the second examination. Chronic gastritis was evaluated, and the level of Helicobacter pylori (HP) colonisation assessed semiquantitatively. The results were compared with age and sex matched non-ulcer controls. The GU series differed from the controls in having a higher degree of HP colonisation in gastric mucosa. The relative risks (RR) in predicting high GU connected with high HP colonisation were significantly elevated, both in the antrum (RR = 6.0-4.8) and in the corpus (RR 5.0-4.4), and still higher when combined HP colonisation values were used (RR 9.5-7.1). The persistence of active ulcer (GU+) was associated with a very high level of HP colonisation, with absence of corpus atrophic gastritis at the first examination and with young patients. Half of the GU+ patients had the maximum grade of combined HP colonisation in both examinations. The study indicates that the presence of HP infection as well as the level of HP colonisation are of importance in both the development and chronicity of peptic GU disease.

[Experience in the diagnosis and treatment of primary biliary liver cirrhosis]. / Opyt diagnostiki i lecheniia pervichnogo biliarnogo tsirroza pecheni.

Altogether 31 cases of primary biliary cirrhosis (PBC) were diagnosed over the period of 1972-1985. All the patients were women (an average age of 51.6). PBC diagnosis was based on the syndrome of chronic intrahepatic cholestasia with prevailing skin itching, mitochondrial antibodies (in 26 patients), an increase in the IgM level (in 23 patients) and specific symptoms in liver biopsy specimens. As a result of late PBC diagnosis most patients were at III-IV morphological stages (17 cases). Immunosuppressive therapy (combination of azathioprine with prednisolone) of the PBC patients insignificantly improved liver parenchymal function though the patients' survival increased. Highly specific methods of PBC diagnosis and treatment necessitate the concentration of PBC patients in specialized centers fitted out with appropriate techniques.

Seven-year follow-up study of chronic gastritis in gastric ulcer patients.

The course of chronic gastritis in the antrum and body was followed up for 7 years in 112 patients with gastric ulcer (GU). As controls served 155 subjects collected at random from the same geographical area. At the start of the study (first examination) there was a slight predominance of antrum gastritis in the series, but during the follow-up period (second examination at 4 years (61 out of 112 patients) and third examination at 7 years (39 out of 112 patients] a distinct body gastritis gradually predominated in GU patients. The healing tendency of active ulcer was accompanied by a more pronounced progression of body gastritis. The rate of body gastritis progression was very rapid and was calculated to be 11-fold as compared with that in the population at large. No immunological phenomena were associated with the body atrophy process.

[Reactions of humoral and cellular immunity in peptic ulcer in relation to the condition of the gastric mucosa]. / Reaktsii gumoral'nogo i kletochnogo immuniteta pri iazvennoi bolezni v zavisimosti ot sostoianiia slizistoi obolochki zheludka.

A total of 160 persons including 50 patients with duodenal ulcer (DU) and 38 with gastric ulcer (GU) were examined for antibodies to the parietal cells of the stomach (PCA) and cell cellular immunity responses to autologous antigen from the gastric mucosa. It was shown that both PCA of the stomach and cell immunity responses in patients with GU and DU occurred in an insignificant number of cases. No differences were revealed in the humoral and cellular immunity in GU and DU persons with and without concomitant gastritis or in the stage of exacerbation and ulcer cicatrization.

Immunology of chronic gastritis.

65 patients with chronic gastritis and 12 controls with normal gastric mucosa were studied for cell-mediated immunity by the means of the lymphocyte blasttransformation and leukocyte migration inhibition tests. In these patients parietal cell antibodies were determined by the indirect immunofluorescence test as well. In 22 patients who had eigher isolated fundal gastritis, isolated antral gastritis or pangastritis cellular immune reactions to fundal or/and antral mucosal antigen extracts were revealed, whereas only 8 had parietal cell antibodies in their sera. It is suggested that for immunological characterization of chronic gastritis the evaluation of cellular immune reactions must be undertaken as well as antibody determinations.

Gastric ulcer, gastritis and gastric carcinoma.

The results of an endoscopic study of the incidence of gastritis and gastric cancer in gastric ulcer in a series of 112 patients 1 to 4 years (mean 2.6 years) after the initial examination are presented. Chronic antral gastritis was found in 48 % of cases and was mainly atrophic. In 10 cases both the antral and body mucosa were normal. In 11 cases the antral mucosa was normal before treatment and remained normal in most of them. During the observation period 5 patients died from other than gastrointestinal diseases. Eleven patients were operated on for complications or relapses of ulcer disease. Gastric cancer was found in 4 cases, the interval between the diagnoses of benign ulcer and cancer was from 1 to 27 months. Elevation of the blood carcinoembryonic antigen (CEA) level was found in 17 cases out of 56 examined and these values remained elevated in most cases at re-examination 3 years later.