Anti-parietal Cell Antibodies Research Articles

Dynamic regulation of gastric autoimmunity by thyroid hormone.

Neonatal thymectomy (NTX) of BALB/c mice between days 1 and 3 post-birth leads to a high incidence of autoimmune gastritis involving T cells and autoantibodies. Although progress has been made in understanding various immunological events associated with that disease process, much remains to be learned about the regulatory factors which control autoimmune gastritis. In this study we have examined the potential for neuroendocrine hormones of the hypothalamus-pituitary-thyroid (HPT) axis to alter the outcome of experimental autoimmune gastritis in NTX mice. As reported here, thyroxine administered to young adult NTX mice during an active phase of disease development dramatically reduced the incidence of gastritis and the overall severity of disease, and lowered the levels of anti-parietal cell antibodies. In contrast, treatment of young NTX mice with thyroxine or other HPT hormones prior to the onset of disease had no beneficial effect on gastritis, but instead resulted in significantly higher anti-parietal cell antibody levels compared to non-hormone-treated NTX mice or to NTX mice treated as adults. Reverse transcriptase spectratype analyses of 22 Vbeta gene junctional sites revealed pronounced oligoclonality and limited junctional diversity in stomach lymphocytes from untreated NTX mice compared to normal mice or thyroxine-treated NTX mice. These findings identify a set of dynamic immune-endocrine interactions, linked to critical development-dependent events, that are involved in the expression and regulation of peripheral autoimmunity.

Immunological and Virological Study of Sudden Deafness

Thirty-three patients with sudden deafness and 11 controls were selected from the patients admitted to the Department of Otolaryngology, Tokai University Hospital from November 1990 to October 1991. Viral titers were measured for mumps, adenovirus, rubella, measles, herpes simplex virus (HSV), varicella zoster virus (VZV), rhinosyncytial virus, cytomegalo-virus (CMV), and mycoplasma pneumoniae in 33 sudden deafness patients and 11 controls at a 2-week interval. In 20 of 33 sudden deafness patients and 5 of 11 controls, autoantibodies of rheumatoid factor (RF), anti-mitochondrial antibody (AMA), anti-nuclear antibody (ANA), anti-parietal cell antibody (APA), anti-smooth muscle antibody (ASA), and anti-type II collagen antibody were studied. Viral titer study did not reveal any significant change either in the patients or in the controls, whereas autoantibody study revealed a relatively high incidence for ASA in the patients as compared with the controls. The relatively high incidence for ASA suggests that immune-mediated processes may be involved in the etiology of sudden deafness.

Nondiabetic Neuropathy in a Patient with Diabetes

A case of peripheral neuropathy in a patient with diabetes who had atypical clinical findings is presented. Because of the atypical initial manifestations and short duration of insulin-dependent diabetes, another cause of the neuropathy was suspected. The presence of vitiligo, hypothyroidism, and diabetes prompted a search for evidence of pernicious anemia. Despite a normal blood cell count, the diagnosis of pernicious anemia was confirmed on the basis of an increased serum gastrin level and antiparietal cell antibody titer. Treatment with vitamin B12 resulted in an arrest, but not a reversal, of the signs of peripheral neuropathy. In patients with diabetes, vitamin B12 deficiency should be suspected; its early diagnosis and treatment are important in minimizing neurologic damage.

Antismooth muscle and antiparietal cell antibodies in Indians with alopecia areata.

Alopecia areata is suspected to be an autoimmune disease. We studied 104 consecutive patients with alopecia areata for the presence of autoantibodies and associated autoimmune diseases. A detailed history and examination was carried out in all patients to look for associated atopy, diabetes mellitus, hypertension, rheumatoid arthritis, vitiligo, lupus erythematosus, and thyroid disorders, etc. in the patients or their family members. Venous blood for estimation of fasting and postprandial blood glucose was collected in 30 patients, especially in those with family history of diabetes mellitus. Antimitochondrial (AMA), antismooth muscle (SMA), antinuclear antibodies (ANA), antiparietal cell antibody (PCA), and antibody against thyroid microsome (TMA) were detected employing indirect immunofluorescence on a composite section of rat liver, stomach, kidney, and human thyroid. Skin biopsy was processed for direct immunofluorescence by a conventional technique. Disseminated discoid lupus erythematosus, lichen planus, urticaria, psoriasis, and seronegative spondylarthritis were associated with alopecia areata in one case each. Antismooth-muscle-antibodies and PCA were found in 36 (34.6%) and 44 (42.3%) patients respectively, followed by TMA in 8 (7.7%), AMA in 6 (5.7%), antithyroglobulin antibodies in 3 (2.8%), and ANA in 2 (1.9%) patients. The incidence of SMA was higher in men with alopecia areata (P < 0.001). Direct immunofluorescence carried out in 24 patients did not reveal significant findings, except for occasional immunoglobulin deposits around hair follicles and blood vessels. Alopecia areata in India is associated more often with antismooth muscle and antiparietal cell antibodies.

Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a

The occurrence of thyroid abnormalities and the appearance of organ- and non-organ-specific autoantibodies during long-term recombinant interferon alpha-2a (IFN-alpha) therapy were studied in 86 and 51 consecutive outpatients with hepatitis C and B virus-related chronic active hepatitis (CAH-HCV and CAH-HBV), respectively. Most patients had longstanding community-acquired hepatitis. At baseline, 9.3% of CAH-HCV and 3.9% of CAH-HBV patients showed clinical and/or biochemical signs of thyroid dysfunction. The remaining patients were euthyroid, although anti-thyroid autoantibodies were found in 33/78 (42.3%) of CAH-HCV and in 5/49 (10.2%) of CAH-HBV patients. During IFN-alpha treatment, increased anti-thyroid autoantibody levels were seen in 40% of CAH-HCV initially negative patients, while they became detectable in no more than 10% of CAH-HBV patients. Interferon-alpha-induced hypo- or hyperthyroidism was recorded in 12 of 35 CAH-HCV patients treated for 12 months (34.3%). Only one CAH-HBV patient developed hyperthyroidism. High titers of anti-nuclear autoantibodies (ANA) were recorded at enrollment in 5/36 (13.8%) of CAH-HCV and in 3/16 (18.7%) of CAH-HBV patients. Only one CAH-HCV patient displayed anti-parietal cell antibodies (PCA). After IFN-alpha treatment, ANA were found in 10/28 (35.7%) and PCA in 2/28 (7.1%) of CAH-HCV patients, while an additional CAH-HBV patient developed PCA, but not ANA. However, no signs of systemic autoimmune disease were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Dépistage de la maladie de Biermer dans un groupe de 120 patients porteurs d'une maladie thyroïdienne autoimmune

Organ specific autoantibodies are frequently detected in patients with autoimmune thyroid diseases (AITD). The aim of this study is the possibility of an early diagnosis of pernicious anemia in AITD. We have examined 120 patients with Graves' disease or Hashimoto's thyroiditis and 25 control subjects. The demonstration of atrophic gastritis has been possible on 8 of 10 patients who have antiparietal cell antibodies and elevated serum gasrin concentrations.

Serum autoantibodies in patients with Alzheimer's disease and vascular dementia and in nondemented control subjects.

In this study we sought to evaluate the clinical significance of serum autoantibodies to dementing processes. We assessed 40 age-matched subjects: 10 patients with probable Alzheimer's disease, 10 with possible Alzheimer's disease with cerebrovascular disease, 10 with vascular dementia, and 10 nondemented control subjects. Serum from each subject was tested for the presence of antithyroglobulin antibody, thyroid antimicrosomal antibody, gastric anti-parietal cell antibody, anti-smooth muscle antibody, antinuclear antibody, rheumatoid factor, antineuronal antibody, and anticardiolipin antibody. In addition, we investigated the sera of these patients for the presence of an antivascular antibody directed against the vascular basement membrane proteoglycan antigen and for circulating immune complexes. Autoantibodies were present in 100% of the patients with possible Alzheimer's disease with cerebrovascular disease, 80% of those with vascular dementia, 40% of those with probable Alzheimer's disease, and 30% of the nondemented control subjects. The highest number of autoantibodies was observed in patients with vascular dementia and possible Alzheimer's disease with cerebrovascular disease. Antinuclear antibody was present in 60% of vascular dementia patients and antineuronal antibody in 50% of these patients. However, no individual autoantibody could differentiate Alzheimer's disease from cerebrovascular disorders. Immune complexes were detected in the serum of 20-30% of each patient group. Neither the patient nor the control sera was found to contain antiendothelial antibody. Despite the relatively small number of individuals examined in each category, the elevated number of autoantibodies associated with possible Alzheimer's disease with cerebrovascular disease and vascular dementia indicates a possible link between the presence of autoantibodies and cerebrovascular disorders in dementia.

Laboratory evaluation of patients with Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytic infiltration of the lacrymal and salivary glands, leading to severe dryness of eyes (keratoconjunctivitis sicca) and mouth (xerostomia). SS may exist as a primary disorder (1 degree-SS) or in association with other autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus or progressive systemic sclerosis (scleroderma). Diagnosis of 1 degree-SS is confirmed by minor salivary gland biopsy and the presence of circulating autoantibodies. Minor salivary gland biopsies exhibit focal lymphocytic infiltrates that are present in the majority of lobules. Incorrect methods of biopsy and failure to determine the average focus score are common causes for false-positive and false-negative biopsies. SS patients frequently have a positive antinuclear antibody test due to presence of SS-A (Ro) and SS-B (La) autoantibodies. Molecular analysis has revealed multiple "SS-A" proteins (60 kd, 54 kd, 52 kd) that react with sera from SS patients, as well as a 48 kd SS-B protein. Rheumatoid factor (anti-IgG Fc antibody) in 1 degree-SS patients exhibits restriction in its light chain-associated idiotype, in contrast to RA patients where no restriction of idiotype was detected. Other autoantibodies found in a subpopulation of SS patients include anti-ADP ribose polymerase, anti-cardiolipin, anti-mitochondrial, anti-mitotic spindle apparatus, anti-parietal cell, and anti-thyroid associated antibodies. Due to the high frequency of dryness syndromes in patients due to other causes (ranging from drug side effects to normal aging processes), the use of strict criteria for diagnosis of SS will lead to improved cost-efficient medical care avoiding needless anxiety in the patient.

自己免疫性溶血性貧血を伴った悪性貧血の一例

A 61-year-old woman with hemolytic anemia was admitted to our hospital. Laboratory findings were as follows: Hb 8.8g/dl, Ht 25.7%, mean corpuscular volume (MCV) 133.9 mean corpuscular hemoglobin (MCH) 45.8. The total bilirubin level was 4.1mg/dl (indirect 3.4mg/dl), the LDH value was 271lu/l, and the haptoglobin level was less than 10mg/dl. The direct antiglobulin (Coombs') test was positive. Serum vitamin B12 was 45pg/dl. Antiparietal cell antibodies and antiintrinsic antibodies were positive. The patient was successfully treated with vitamin B12 injection under a diagnosis as pernicious anemia associated with autoimmune hemolytic anemia.Although both pernicious anemia and autoimmune hemolytic anemia are thought to be caused by autoimmune mechanisms, reported case of pernicious anemia associated with autoimmune hemolytic anemia is very rare.

Prevalence of anticardiolipin antibodies in the elderly British population

In a cross-sectional study of 100 healthy elderly individuals, anticardiolipin antibodies (aCL) were measured using an ELISA technique. aCL were not detected in the majority of subjects (63%), and in the remaining 37% titres were within the laboratory reference range (mean +5 standard deviations) previously determined for adults of all ages. In contrast, significant titres of IgM rheumatoid factor were found in 10%, antimitochondrial antibody in 13%, antinuclear factor in 5%, anti-smooth muscle antibody in 18%, antiparietal cell antibody in 10%, and antireticulin antibody in 1%. Antibodies to single or double-stranded DNA were not detected in any subject. We conclude that, although other auto-antibodies may be present in the healthy aging population in Britain, abnormally elevated levels of aCL antibody do not occur, and when present may be an indicator of autoimmune-mediated pathology.

Gastrites atrophiques fundiques et anémies par carence en fer chez la jeune femme : étude critique à propos de 3 observations

Among 50 patients with iron deficiency anemia, 3 young women (17 to 38 y.o) presented with atrophic and achlorhydric chronic gastritis as the sole cause of the disease. Fundic atrophy (3/3), hypergastrinemia (3/3) ranging from 725 to 1068 pg/ml and anti parietal gastric cell antibodies (2/3) were present. Seric folatemia and B 12 vitaminemia were normal ; anti-intrinsic factor antibodies were absent. Iron and ascorbic acid intakes were normal. The authors discuss the interrelations between iron deficiency, « type Achronic gastritis and latent pernicious anemia.

Serum lmmunglobulin and Complement Levels in the Patients With Head and Neck Carcinoma and the Evaluation of Autoantibody Positivity Rate

Serum lmmunglobulin and Complement Levels in the Patients With Head and Neck Carcinoma and the Evaluation of Autoantibody Positivity Ratein this study, smooth muscle antibody (SMA), anti-nücleer antibody (ANA) anti- mitochondrial antibody (AMA), anti-parietal cell antibody (PA), antiglomerular basal membrane antibody (GM), serum immunglobulins and complement-C3 levels have been searched. The positivity rate of ANA (31.91 %) and SMA (38.29 %) were found high in sera of the patients with head and neck carcinoma which had been diagnosed histopathologically. But the positivity rate of AMA (4.25 %) PA (12.76 %) and GM (2.12 %) were low in the same group. ANA and SMA were detected in 1 O of 30 patients with laryngeal carcinoma; ANA were detected in 5 of 9 patients (55.5 %) and SMA were found in 4 of 9 patients (44.5 %) with nasopharyngeal carcinoma. There was no significant deviation in the levels of immunglobulins and complement-C3. The highest levels of immunoglobulins have been detected in patients with laryngeal carcinoma. Finding of high positivity rate of ANA and SMA in the patients with head and neck carcinoma showed an accordance with the other investigators' results.

Parietal cell autoantigens involved in neonatal thymectomy-induced murine autoimmune gastritis. Studies using monoclonal autoantibodies

Autoimmune gastritis accompanied by autoantibodies to parietal cells was induced in BALB/c nu/+ mice by neonatal thymectomy 2–4 days after birth. Three monoclonal autoantibodies, designated as 2B6 (IgG1), 2G10 (IgG2b), and 1H9 (IgG1), were obtained from one of these mice. All three reacted specifically with parietal cells, 2G10 recognizing species-specific antigenic determinants and 2B6 and 1H9 recognizing interspecies-specific antigenic determinants. All three recognized antigens on the membrane of intracellular secretory canaliculi and the cytoplasmic tubulovesicular system of parietal cells. At least two different molecular groups were recognized by these antibodies; 2B6 recognizing a 65,000–79,000-mol wt group and 1H9 recognizing a 92,000–120,000-mol wt group. Sera of most mice with autoimmune gastritis reacted with either or both groups. Both groups were consistently coprecipitated by any of the three antibodies when solubilized in NP-40. Sera, from patients with pernicious anemia, containing anti-parietal cell antibodies could also precipitate these two groups of antigens. Competition assay and physicochemical studies showed that the epitopes recognized by the three monoclonal antibodies are different.

Pepsinogens and other serum markers in pernicious anemia.

Pepsinogen (PG) I and PG II levels were determined in sera from 147 patients with pernicious anemia. Race, sex, age, gastrin level, and antibody status did not influence pepsinogen levels. PG I values less than 30 micrograms/L were found in 92% of cases and PG I to PG II ratios less than 3.0 in 82% of cases. At least one of these two results was abnormal in 97% of all patients with pernicious anemia. In comparison, results of other blood tests used in the investigation of pernicious anemia were less often abnormal. Serum gastrin level exceeded 200 ng/L in 90% of patients with pernicious anemia and was second to pepsinogen abnormality in diagnostic sensitivity. Results for anti-intrinsic factor antibody were positive in 73% of cases and anti-parietal cell antibody in only 52%. Although its specificity is limited, the presence of low PG I level and/or low PG I-PG II ratio is currently the most sensitive serum indicator for pernicious anemia, and absence of both can be taken as a strong argument against the diagnosis. This highly sensitive test can be combined further with the highly specific serum anti-intrinsic factor antibody test for the presumptive diagnosis of pernicious anemia when definitive tests (the Schilling test or gastric analysis for intrinsic factor) cannot be done or results are inconclusive.

Implications of circulating autoantibodies and peripheral blood lymphocyte subsets for the genesis of premature ovarian failure

Several kinds of circulating autoantibodies and peripheral blood lymphocyte subsets were studied in 20 patients with secondary amenorrhea manifesting hormonal and clinical features of premature ovarian failure (POF). More than one kind of autoantibody was detected in 14 patients (70%). Seven patients (35%) had anti-thyroglobulin antibody, 6 (30%) had anti-parietal cell antibody, 8 (40%) had anti-nuclear antibody, and one patient with chronic thyroiditis had anti-TSH receptor antibody. Anti-adrenal cortex antibody and RA test were negative in all patients. Two patients had clinically evident autoimmune disease; one had myasthenia gravis and the other had chronic thyroiditis. Examination of peripheral blood lymphocyte subsets of 19 patients by flow cytometry revealed an increase in the percentage of OKT3+ cells and OKT4+ cells and a decrease in OKT8+ cells in POF patients compared with age-matched controls, but these differences were not significant. An increase in the OKT4/OKT8 ratio was, however, significant. It has been suggested that an autoimmune mechanism may participate in the genesis of POF, at least in patients with autoimmune diseases; however, the findings in this study support the hypothesis that some pure POF may also be caused by an autoimmune process resulting from a subclinical imbalance in the immunoregulatory system before manifestation of the autoimmune disease.

Lymphocyte surface phenotypes in pernicious anemia.

Because an immunological defect of an unknown nature is thought to be a factor in the pathogenesis of pernicious anemia, we studied lymphocyte surface phenotypes in 40 patients and compared them with 113 healthy controls. The only significant difference that emerged was in their slightly decreased number and proportion of surface immunoglobulin (lambda chain) -bearing cells. Of specific interest, the numbers of OKT4+ and OKT8+ lymphocytes and the T4+/T8+ ratios were not significantly different from control values. A sizable minority of patients had increased ratios, while a smaller number had decreased values. No explanation or identifying feature was apparent for those patients with either increased or decreased T4+/T8+ ratios. (One patient with a very low ratio, who was excluded from our analysis, developed acquired immune deficiency syndrome.) No differences were apparent in T4+/T8+ ratios or any other lymphocyte surface phenotypic characteristics when patients were segregated by presence of anti-intrinsic factor antibody or anti-parietal cell antibody, or by race, sex, or age. Our results in a racially heterogeneous group of patients do not support the suggestion that T4+/T8+ ratios are usually abnormal in prenicious anemia or that the presence of anti-intrinsic factor antibody is associated with such abnormality.

Spontaneous nonneoplastic gastric lesions in female Han:NMRI mice, and influence of food restriction throughout life.

A life span study of 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline, and 300 of a lean subline) was done to determine the occurrence of spontaneous disease with ad libitum or restricted feeding. Major nonneoplastic lesions in the glandular stomach were erosions, ulcers and adenomatous hyperplasia of the fundus. Ulcers, ranging in incidence with ad libitum feeding from 5 to 9% and with food restriction from 13 to 34%, either occurred secondary to other diseases or were due to stress associated with food restriction, causing death mainly in the lean subline. Adenomatous hyperplasia was most common in the control group (41%); the frequency increased with age and was significantly reduced by food restriction. The etiology of adenomatous gastric hyperplasia is yet unknown. However, a lack of antiparietal cell antibodies, as determined by an immunofluorescent technique, indicates that an autoimmune disorder is not involved and an increase in antral gastrin cells, as determined by avidin-biotin peroxidase immunocytochemistry, suggests a hormonal involvement in pathogenesis.

Sjögren's Syndrome Associated with Vitamin B12Deficiency

Three patients showing Sjögren's syndrome in association with macrocytic anemia due to vitamin B(12) deficiency are described. Antibodies to parietal cells, intrinsic factor and salivary protein were investigated; positive test results were obtained in different combinations. Addisonian pernicious anemia as well as vitamin B(12)-malabsorption because of anti-intrinsic factor antibodies in gastric juice and/or malabsorption due to changes in the intestinal wall induced by Sjögren's syndrome are possible etiological factors. A case of Sjögren's syndrome associated with positive anti-parietal cell antibodies and histaminerefractory achylia is also reported. The concurrence of these two diseases known to be associated with autoimmune responses suggests the possibility of similar pathogenesis.

Age-related anti-thyroid antibodies and thyroid abnormalities in Turner syndrome.

One hundred pediatric patients with Turner syndrome were studied to determine the correlation between the presence of anti-thyroid antibodies with age and karyotype, and the value of anti-thyroid antibody titers as predictors of subsequent thyroid abnormalities. (54 patients = 45,X; 46 = other karyotypes.) The frequency of positive titers of anti-thyroid antibodies increased linearly with cumulative age. Anti-parietal cell and anti-adrenocortical cell antibodies were not increased in these patients (1.3 and 2.6% respectively). The ability to use positive anti-thyroid antibody titers to predict the development of thyroid abnormalities increased from age 10 years and became statistically significant at ages 13-17 years for the whole group as well as 45,X patients. None of the patients had clinical symptoms of thyroid dysfunction although 22% developed thyroid abnormalities, which included elevated TSH, low T4, and/or goiter.

Electrical membrane responses to secretagogues in parietal cells of the rat gastric mucosa in culture.

Fragments of the gastric fundus of 6-8-day-old rats were maintained in tissue culture. From the explant, adhered to a plastic substrate, epithelial cells migrated and developed to form a monolayer colony. Histological and histochemical studies as well as indirect immunofluorescence studies using anti-parietal cell antibodies testified to the presence of parietal cells in the monolayer during the first week. These parietal cells were distinguished by their vesicular cytoplasmic structures using phase-contrast or differential interference-contrast microscopy. Acridine Orange, an optical probe of H+ accumulation, was taken up preferentially by these parietal cells, exhibiting orange fluorescence within the cells on the third day of culture, in response to stimulation with gastrin, histamine and carbachol. The resting potential of these cultured parietal cells was about -20 mV. On day 2-4 of culture, the cell membrane became hyperpolarized (up to -30 to -40 mV) in response to gastrin, carbachol or histamine in the presence of isobutylmethyl-xanthine (IMX). During hyperpolarization, the membrane resistances decreased significantly. The amplitude and the polarity of secretagogue-induced responses were found to be dependent on the extracellular concentration of K+ (but not Na+ and Cl-). The carbachol-induced responses were inhibited by atropine but not curare. The responses induced by histamine plus IMX were blocked by cimetidine but not pyrilamine. Neither atropine nor cimetidine affected the gastrin-evoked responses. It is concluded that rat parietal cells have separate receptors for acetylcholine (muscarinic), gastrin and histamine (H2), and that an increase in the membrane permeability to K+ is closely associated with the responses of these receptors under these in vitro conditions.