Parietal Cell Autoantibodies Research Articles

Improving the Diagnosis of Autoimmune Gastritis: From Parietal Cell Antibodies to H+/K+ ATPase Antibodies.

Parietal cell autoantibodies (PCAs), which recognize the enzyme H+/K+-ATPase as a target, are considered to be a diagnostic marker of autoimmune gastritis and pernicious anemia; these conditions are characterized by the presence of corpus atrophic gastritis. Circulating PCAs can be detected using several analytical methods that are commonly available in the clinical laboratory. Traditionally, indirect immunofluorescence (IIF) on rodent or primate stomach tissue is used as a screening test for the detection of PCAs. However, IIF suffers from a high inter-observer variability and lacks standardization. In addition, like immunoblotting, results are expressed only in a qualitative or semi-quantitative manner. Based on the few available studies that are reviewed herein, quantitative enzyme-linked immunosorbent assays (ELISAs) and fluorescence enzyme immunoassays (FEIAs) using purified H+/K+-ATPase perform better than IIF in the detection of PCAs, displaying higher sensitivity and utility in monitoring the disease. In light of their higher diagnostic accuracy, these solid-phase methods should be preferred to IIF in the screening of autoimmune atrophic gastritis. The use of methods to detect antibodies versus a specific subunit of H+/K+-ATPase (α or β) is currently confined to the world of research. Further investigation is required to define the clinical utility of H+/K+-ATPase subunit detection.

Update on Serum Biomarkers in Autoimmune Atrophic Gastritis.

Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important. The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods. Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.

Autoantibodies Toward ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase Are Reliable Serological Pre-endoscopic Markers of Corpus Atrophic Gastritis.

INTRODUCTION:Noninvasive assessment of corpus atrophic gastritis (CAG), a condition at increased risk of gastric cancer, is based on the measurement of pepsinogens, gastrin, and Helicobacter pylori antibodies. Parietal cell autoantibodies (PCAs) against the gastric proton pump (ATP4) are potential serological biomarkers of CAG. The purpose of this study was to compare the diagnostic performance of PCA and pepsinogen I tests in patients with clinical suspicion of CAG with the histopathological evaluation of gastric biopsies as reference standard.METHODS:A prospective case-finding study was performed on 218 naive adult patients (131 women, median age 65 years) who underwent gastric biopsies to confirm/exclude CAG. Patients with histopathological CAG were defined as cases, conversely as controls. Autoantibodies against the individual alpha (ATP4A) and beta (ATP4B) subunits of ATP4 were measured by luciferase immunoprecipitation, and global PCA and pepsinogen I by enzyme-linked immunosorbent assay.RESULTS:Histopathology classified 107 subjects (49%) as cases (CAG+, autoimmune 81.2%, and multifocal extensive 18.8%) and 111 subjects (51%) as controls (CAG−). In cases, ATP4A, ATP4B, and PCA titers were increased compared with controls, whereas pepsinogen I was reduced (P < 0.0001 for all). ATP4B, ATP4A, and pepsinogen I tests showed sensitivities of 77%, 75%, and 73% and specificities of 88%, 88%, and 80%, respectively. The receiver operating characteristic (ROC) area under the ROC curve (AUC) of these serological biomarkers confirmed their ability to discriminate cases from controls (ATP4B = 0.838, ATP4A = 0.826, pepsinogen I = 0.775, and PCA = 0.805), whereas the partial ROC-pAUC90 analysis showed that the ATP4B test had the best diagnostic performance (P = 0.008 vs ATP4; P = 0.0002 vs pepsinogen I). The presence of autoimmune or extensive gastritis was not significantly different between ATP4B positive or negative cases (P = 0.217).DISCUSSION:PCAs are promising serological biomarkers for the identification of CAG in high-risk individuals, particularly in an autoimmune pattern but also in an extensive-multifocal atrophy pattern.

Gastric parietal cell and thyroid autoantibodies in patients with burning mouth syndrome

Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in burning mouth syndrome (BMS) patients. Serum GPCA, TGA, and TMA levels were measured in 884 BMS patients and in 442 age- and sex-matched healthy control subjects. We found that 12.3%, 21.6%, and 22.7% of 884 BMS patients and 1.8%, 2.3%, and 2.9% of 442 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. BMS patients had significantly higher frequencies of GPCA, TGA, and TMA positivities than healthy control subjects (all P-values<0.001). We also found that 20 (2.3%), 130 (14.7%), and 181 (20.5%) BMS patients and 3 (0.7%), 8 (1.8%), and 6 (1.4%) healthy control subjects had the presence of three (GPCA+TGA+TMA), two (GPCA+TGA, GPCA+TMA, or TGA+TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 255 TGA/TMA-positive BMS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.8%, 5.1%, and 7.1% of these TGA/TMA-positive BMS patients had normal, lower, and higher serum TSH levels, respectively. Approximately 37.5% of 884 BMS patients have serum GPCA/TGA/TMA positivity. Moreover, 12.3%, 21.6%, and 22.7% of 884 BMS patients have the serum GPCA, TGA, and TMA positivities, respectively. Only 5.1% and 7.1% of TGA/TMA-positive BMS patients have hyperthyroidism and hypothyroidism, respectively. It needs further studies to know whether GPCA-positive BMS patients may finally become as having autoimmune atrophic gastritis.

Vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy: a case report and literature review.

Pseudo-thrombotic microangiopathy (pseudo-TMA) is a recognized, yet uncommon, clinical presentation of vitamin B12 deficiency. Patients with pseudo-TMA present with microangiopathic hemolytic anemia (MAHA), thrombocytopenia and schistocytes. They are often misdiagnosed as thrombotic thrombocytopenia purpura (TTP) and receive unnecessary therapy. Here, we report a case of a 60-year-old male who presented with thrombocytopenia and normocytic normochromic anemia. Anemia work-up was remarkable for severe B12 deficiency (<60 pg/mL) and a positive non-immune hemolysis panel. Peripheral smear was reviewed and showed anisocytes, poikilocytes, schistocytes and hypersegmented neutrophils. Vitamin B12 replacement (1000 mcg IM daily) was started, ADAMTS13 activity was sent and daily plasmapheresis was initiated. Over the next 3 days, the patient’s hemoglobin and platelets were stable and the hemolysis panel showed gradual improvement. On day 4, ADAMTS13 activity results came back normal at 61%. Accordingly, plasmapheresis was discontinued, parenteral B12 replacement was continued and that resulted in gradual improvement and eventually cessation of hemolysis and normalization of hemoglobin and platelets. In this patient, parietal cell autoantibodies were positive and so the diagnosis of pernicious anemia was made. Patients with severe vitamin B12 deficiency may present with features mimicking TTP such as MAHA, thrombocytopenia and schistocytosis. An early and accurate diagnosis of pseudo-TMA has a critical clinical impact with respect to administering the correct treatment with vitamin B12 replacement and avoiding, or shortening the duration of, unnecessary therapy with plasmapheresis.

Gastric parietal cell and thyroid autoantibodies in patients with atrophic glossitis

Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of presence of serum GPCA, TGA, and TMA in atrophic glossitis (AG) patients. Serum GPCA, TGA, and TMA levels were measured in 1064 AG patients and in 532 age- and sex-matched healthy control subjects. We found that 26.7%, 28.4%, and 29.8% of 1064 AG patients and 2.3%, 2.1%, and 2.6% of 532 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. AG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values<0.001). We also found that 67 (6.3%), 181 (17.0%), and 340 (32.0%) AG patients and 3 (0.6%), 10 (1.9%), and 8 (1.5%) healthy control subjects had the presence of three (GPCA+TGA+TMA), two (GPCA+TGA, GPCA+TMA, or TGA+TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 373 TGA/TMA-positive AG patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 78.6%, 8.0%, and 13.4% of these TGA/TMA-positive AG patients had normal, lower, and higher serum TSH levels, respectively. Approximately 55.3% of 1064 AG patients have serum GPCA/TGA/TMA positivity. Because part of GPCA-positive AG patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive AG patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these autoantibody-positive AG patients should be referred to medical doctors for further management.

When the diagnosis is difficult to digest: severe vitamin B12 deficiency secondary to pernicious anemia mimicking life-threatening thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is an uncommon yet life-threatening condition, usually marked by a classic pentad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, acute kidney injury (AKI), neurological disturbances, and fevers. Prompt recognition and treatment is essential to reduce morbidity and mortality. The rarity and variability of presentations, however, makes this a difficult diagnosis to make reliably, and in many cases, treatment is initiated empirically before the appropriate diagnostic testing is completed. After TTP and other common causes of thrombotic microangiopathy (TMA) have been excluded, evaluation for causes of “pseudo”-thrombotic microangiopathy (“pseudo”-TMA) should be pursued. Herein, we present a case of a young man with a history of previously treated hepatitis C virus (HCV) infection presenting with a syndrome concerning for TTP: MAHA, thrombocytopenia, and dizziness with gait ataxia. Disseminated intravascular coagulation (DIC) and autoimmune hemolysis were quickly ruled out, and plasma exchange was emergently initiated. Further workup identified an undetectably low vitamin B12 level with profound elevations in both homocysteine and methylmalonic acid (MMA) levels. Folate and vitamin B12 were replenished, with a rapid resolution of hemolysis and improvement in both the platelet count and hemoglobin that allowed for plasma exchange to be permanently discontinued. Further workup identified positivity of both intrinsic factor and parietal cell autoantibodies, suggesting a diagnosis of pernicious anemia. He was determined to have “pseudo”-TMA secondary to critical vitamin B12 deficiency. The patient was safely discharged home with scheduled subcutaneous vitamin B12 injections along with outpatient follow-up with both Hematology and Gastroenterology.

Gastric parietal cell and thyroid autoantibodies in recurrent aphthous stomatitis patients with concomitant oral lichen planus.

Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) have not yet been reported in recurrent aphthous stomatitis (RAS) patients with concomitant oral lichen planus (OLP/RAS patients). This study mainly assessed the frequencies of serum GPCA, TGA, and TMA (GPCA/TGA/TMA) positivities in 44 OLP/RAS patients. The frequencies of serum GPCA/TGA/TMA positivities in 44 OLP/RAS patients, OLP/RAS patients of four different subgroups, 520 RAS patients, and 352 healthy control subjects were calculated and compared. We found that 20.5%, 27.3%, and 31.8% of 44 OLP/RAS patients, 75.0%, 100.0%, and 100.0% of 4 OLP/major-typed RAS (OLP/major RAS) patients, 15.0%, 20.0%, and 25.0% of 40 OLP/minor-typed RAS (OLP/minor RAS) patients, 45.5%, 72.7%, and 54.5% of 11 atrophic glossitis-positive OLP/RAS (AG+OLP/RAS) patients, and 12.1%, 12.1%, and 24.2% of 33 AG-negative OLP/RAS (AG־OLP/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. OLP/RAS patients and OLP/RAS patients of four different subgroups all had significantly higher frequencies of GPCA/TGA/TMA positivities than healthy control subjects. Moreover, OLP/RAS patients had a significantly higher frequency of TMA positivity than RAS patients, and OLP/major RAS and AG+OLP/RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than RAS patients. Furthermore, OLP/major RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than OLP/minor RAS patients. For OLP/RAS patients, the concomitant OLP may play a role in causing an increased frequency of TMA positivity, and major RAS and the concomitant AG are contributory factors causing the elevated frequencies of GPCA/TGA/TMA positivities.

Gastric parietal cell and thyroid autoantibodies in Behcet's disease patients with or without atrophic glossitis.

Behcet's disease (BD) patients should have recurrent aphthous stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study mainly assessed the frequencies of serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities in 30 AG-positive RAS/BD (AG+RAS/BD) and 33 AG-negative RAS/BD (AG־RAS/BD) patients. The frequencies of serum GPCA, TGA, and TMA positivities in 30 AG+RAS/BD patients, 33 AG־RAS/BD patients, and 126 healthy control subjects were calculated and compared. We found that 20.0%, 30.0%, and 26.7% of 30 AG+RAS/BD patients, 9.1%, 12.1%, and 15.2% of 33 AG־RAS/BD patients, and 1.6%, 2.4%, and 2.4% of 126 healthy control subject had the presence of GPCA, TGA, and TMA in their sera, respectively. The 30 AG+RAS/BD patients had significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects (all P-values<0.001). The 33 AG־RAS/BD patients had a higher frequency of serum TGA positivity (P=0.051, marginal significance) and a significantly higher frequency of serum TMA positivity (P=0.011) than healthy control subjects. Although the 30 AG+RAS/BD patients had higher frequencies of serum GPCA, TGA, and TMA positivities than the 33 AG־RAS/BD patients, the differences were not significant. AG+RAS/BD patients do have significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects. This finding indicates that the concomitant presence of AG may result in significantly elevated frequencies of serum GPCA, TGA, and TMA positivities in BD patients.

Gastric parietal cell and thyroid autoantibodies in patients with Behcet's disease.

Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) were rarely examined in Behcet's disease (BD) patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients. The frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients, 19 major-typed recurrent aphthous stomatitis (RAS)/BD (major RAS/BD) patients, 44 minor-typed RAS/BD (minor RAS/BD) patients, 520 RAS patients, and 126 healthy control subjects were calculated and compared. We found that 14.3%, 20.6%, and 20.6% of 63 BD patients, 21.1%, 21.1%, and 26.3% of 19 major RAS/BD patients, 11.4%, 20.5%, and 18.2% of 44 minor RAS/BD patients, 11.5%, 18.5%, and 18.3% of 520 RAS patients, and 1.6%, 2.4%, and 2.4% of 126 healthy control subjects had serum GPCA, TGA, and TMA positivities, respectively. BD, major RAS/BD, minor RAS/BD, and RAS patients all had significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects (all P-values<0.05). However, there were no significant differences in different serum autoantibody frequencies between BD, major RAS/BD, or minor RAS/BD patients and RAS patients. Of 16 TGA/TMA-positive BD patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.5%, 6.3%, and 6.3% of these TGA/TMA-positive BD patients had normal, lower, and higher serum TSH levels, respectively. Approximately 35% BD patients have serum GPCA/TGA/TMA positivity. However, BD patients do not have significantly higher frequencies of serum GPCA, TGA, and TMA positivities than RAS patients.

Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management.

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that occurs more frequently in middle-aged and elderly female patients. Previous studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune disease. Clinically, six types of OLP, namely reticular, papular, plaque-like, atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral and symmetric distribution of the oral lesions. Plaque-like and atrophic/erosive OLP may be misdiagnosed as oral leukoplakia and oral erythroleukoplakia, respectively. Our previous study found serum autoantibodies in 195 (60.9%) of the 320 OLP patients. Specific serum anti-nuclear, anti-smooth muscle, anti-mitochondrial, gastric parietal cell, thyroglobulin, and thyroid microsomal autoantibodies are present in 28.1%, 8.4%, 1.6%, 26.3%, 21.3%, and 24.4% of 320 OLP patients, respectively. Furthermore, we also discovered that 21.9%, 13.6%, 7.1%, 0.3%, and 14.8% of 352 OLP patients have hemoglobin, iron, vitamin B12, and folic acid deficiencies, and abnormally high serum homocysteine level, respectively. Therefore, it is very important to examine the serum autoantibody, hematinic and homocysteine levels in OLP patients before starting the treatments for OLP patients. Because OLP is an immunologically-mediated disease, corticosteroids are the drugs of choice for treatment of OLP.

Conversion to Graves disease from Hashimoto thyroiditis: a study of 24 patients.

The conversion of Hashimoto's thyroiditis (HT) to hyperthyroidism due to thyrotropin receptor antibodies is intriguing and considered rare. The contribution of TSH receptor blocking antibodies (TRAb), which may be stimulators (TSAb) or blockers (TBAb), is suspected. We describe clinical and biological variables in a series of patients switching from Hashimoto's thyroiditis to Grave's disease. Retrospective case study of 24 patients with Hashimoto's thyroiditis followed during 48 ± 36 months that developed later Graves' disease (GD). These variables were analysed in the hypo and hyperthyroid phase: age, sex, initial TSH, free triiodothyronine (fT3), free thyroxine (fT4), anti-TPO, TBII antibodies, parietal cell autoantibodies, time between hypo and hyperthyroidism, thyroid volume and levothyroxine doses (LT). In HT, mean TSH was 9.4 ± 26.1 UI/L and levothyroxine treatment was 66.2 ± 30.8 µg/day. The switch to GD was observed 38 ± 45 months after HT diagnosis. As expected, we found significant differences on TSH, FT3, FT4 and TBAb levels. Three out of 14 patients had parietal cell autoantibodies. In two of these three cases there was an Helicobacter pylori infection. There were no significant differences between HT and GD groups with respect to thyroid volume. To our knowledge, large series documenting the conversion of HT to GD are scarce. Although rare, this phenomenon should not be misdiagnosed. Suspicion should be raised whenever thyroxine posology must be tapered down during the follow-up of HT patients. Further immunological and genetic studies are needed to explain this unusual autoimmune change.

Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients.

Objectives:Circulating autoantibodies targeting the H+/K+-ATPase proton pump of gastric parietal cells are considered markers of autoimmune gastritis, whose diagnostic accuracy in atrophic body gastritis, the pathological lesion of autoimmune gastritis, remains unknown. This study aimed to assess autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase in atrophic body gastritis patients and controls.Methods:One-hundred and four cases with atrophic body gastritis and 205 controls were assessed for serological autoantibodies specific for ATP4A or ATP4B subunits using luminescent immunoprecipitation system (LIPS). Recombinant luciferase-reporter-fused-antigens were expressed by in vitro transcription-translation (ATP4A) or after transfection in Expi293F cells (ATP4B), incubated with test sera, and immune complexes recovered using protein-A-sepharose. LIPS assays were compared with a commercial enzyme immunoassay (EIA) for parietal cell autoantibodies.Results:ATP4A and ATP4B autoantibody titers were higher in cases compared to controls (P<0.0001). The area under the receiver-operating characteristic curve was 0.98 (95% CI 0.965–0.996) for ATP4A, and 0.99 (95% CI 0.979–1.000) for ATP4B, both higher as compared with that of EIA: 0.86 (95% CI 0.809–0.896), P<0.0001. Sensitivity-specificity were 100–89% for ATP4A and 100–90% for ATP4B assay. Compared with LIPS, EIA for parietal cell autoantibodies showed a lower sensitivity (72%, P<0.0001) at a similar specificity (92%, P=0.558).Conclusions:Positivity to both, ATP4A and ATP4B autoantibodies is closely associated with atrophic body gastritis. Both assays had the highest sensitivity, at the cost of diagnostic accuracy (89 and 90% specificity), outperforming traditional EIA. Once validated, these LIPS assays should be valuable screening tools for detecting biomarkers of damaged atrophic oxyntic mucosa.

Antigastric parietal cell and antithyroid autoantibodies in patients with recurrent aphthous stomatitis.

Anti-gastric parietal cell antibody (GPCA), anti-thyroglobulin antibody (TGA), and anti-thyroid microsomal antibody (TMA) have not yet been reported in patients with recurrent aphthous stomatitis (RAS). This study mainly assessed the frequencies of the presence of serum GPCA, TGA, and TMA in different types of RAS patients. Serum GPCA, TGA, and TMA levels were measured in 355 RAS patients of different subtypes and in 355 age- and sex-matched healthy control individuals. We found that 13.0%, 19.4%, and 19.7% of 355 RAS patients, 16.7%, 23.3%, and 21.7% of 60 major-typed RAS patients, 12.2%, 18.6%, and 19.3% of 295 minor-typed RAS patients, 18.1%, 20.0%, and 21.9% of 160 atrophic glossitis-positive RAS (AG+/RAS) patients, and 8.7%, 19.0%, and 17.9% of 195 AG-negative RAS (AG-/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. RAS, major-typed RAS, minor-typed RAS, AG+/RAS, and AG-/RAS patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control individuals (all p<0.001). Of 65 TGA/TMA-positive RAS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 76.9%, 12.3%, and 10.8% of these TGA/TMA-positive RAS patients had normal, lower, and higher serum TSH levels, respectively. We conclude that approximately one-third RAS patients may have GPCA/TGA/TMA positivity in their sera. Because some GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and some TGA/TMA-positive patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these patients should be referred to doctors for further management.

Antigastric parietal cell and antithyroid autoantibodies in patients with desquamative gingivitis.

Desquamative gingivitis (DG) is principally associated with erosive oral lichen planus (EOLP), mucous membrane pemphigoid (MMP), and pemphigus vulgaris (PV). Serum autoantibodies including antigastric parietal cell antibody (GPCA), antithyroglobulin antibody (TGA), and antithyroid microsomal antibody (TMA) were measured in 500 patients with DG, 287 EOLP without DG (EOLP/DG- ) patients, and 100 healthy control subjects. The 500 patients with DG were diagnosed as having EOLP in 455 (91%), PV in 40 (8%), and MMP in five (1%) patients. We found that 37.0%, 43.6%, and 42.6% of 500 patients with DG, 39.6%, 46.4%, and 45.1% of 455 EOLP with DG (EOLP/DG) patients, and 18.5%, 27.5%, and 30.3% of 287 EOLP/DG- patients had the presence of GPCA, TGA, and TMA in their sera, respectively. DG, EOLP/DG, and EOLP/DG- patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). Moreover, 455 EOLP/DG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than 287 EOLP/DG- patients (all P-values < 0.001). Of 210 TGA/TMA-positive patients with DG whose serum thyroid-stimulating hormone (TSH) levels were measured, 84.3%, 6.7%, and 9.0% patients had normal, lower, and higher serum TSH levels, respectively. We conclude that 73.4% DG, 77.1% EOLP/DG, and 47.4% EOLP/DG- patients may have GPCA/TGA/TMA positivity in their sera. Because part of GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive patients may have thyroid dysfunction, these patients should be referred to medical department for further management.

Blood examination is necessary for oral mucosal disease patients.

According to the World Health Organization (WHO), anemia or hemoglobin deficiency is defined as having a hemoglobin concentration 12.4 mM). Serum gastric parietal cell autoantibody (GPCA) positivity may induce destruction of gastric parietal cells and subsequently result in failure of production of intrinsic factor and absorption of vitamin B12 from the terminal ileum, finally leading to vitamin B12 deficiency. Because anemia and hematinic deficiencies may cause or aggravate oral mucosal diseases such as atrophic glossitis (AG), burning mouth syndrome (BMS), oral lichen planus (OLP), recurrent aphthous ulcerations (RAU), or oral submucous fibrosis (OSF), in our oral mucosal disease clinic, complete blood count, serum iron, vitamin B12, folic acid and homocysteine levels, and serum GPCA titers are usually examined to check whether patients with these 5 diseases have microcytic, normocytic or macrocytic

Factors contributing to high levothyroxine doses in primary hypothyroidism: an interventional audit of a large community database.

While few hypothyroid patients require more than the expected weight-related dose of levothyroxine, the underlying causes of larger-than-expected dosing requirements have not been studied in a single cohort. Our aim was to determine and quantify the multiple factors contributing to high-dose levothyroxine requirements in a cohort of patients with hypothyroidism. The Grampian Automated Follow-Up Register (GAFUR) monitors around 17,500 hypothyroid patients. In 2008, 190 (1%) patients took >225 μg of levothyroxine daily. A questionnaire was sent to 174 patients (16 were untraceable) to assess causes and to offer blood tests for endomysial, parietal cell (PCA), and thyroid peroxidase (TPO) autoantibodies. Primary care practices were contacted for medication details. All patients with positive endomysial autoantibodies were referred to a gastroenterologist. Thyroid function tests and levothyroxine doses were re-evaluated in 2011. A total of 125 questionnaires (72%) were returned. Mean levothyroxine dose was 248 μg daily. Twenty-six patients (20.8%) took medication known to interfere with levothyroxine absorption, and 21 patients (16.8%) admitted to compliance issues. Seven patients had positive anti-endomysial antibodies on initial screening, with four being new diagnoses of celiac disease, and PCA were positive in 27 (21.6%) patients. At follow-up in 2011, the mean levothyroxine dose had decreased in patients on interfering medications and in the four new cases of celiac disease. Causes of patients needing high-dose levothyroxine replacement include poor compliance, medication interference, PCA (as a marker of atrophic/autoimmune gastritis), and celiac disease. Doses can be decreased following advice regarding medication or after management of underlying conditions.

Factors contributing to high levothyroxine doses in primary hypothyroidism; an interventional audit of a large community database

Background: While few hypothyroid patients require more than the expected weight-related dose of levothyroxine, the underlying causes of larger-than-expected dosing requirements have not been studied in a single cohort. Our aim was to determine and quantify the multiple factors contributing to high-dose levothyroxine requirements in a cohort of patients with hypothyroidism. Methods: The Grampian Automated Follow-Up Register (GAFUR) monitors around 17,500 hypothyroid patients. In 2008, 190 (1%) patients took >225 μg of levothyroxine daily. A questionnaire was sent to 174 patients (16 were untraceable) to assess causes and to offer blood tests for endomysial, parietal cell (PCA), and thyroid peroxidase (TPO) autoantibodies. Primary care practices were contacted for medication details. All patients with positive endomysial autoantibodies were referred to a gastroenterologist. Thyroid function tests and levothyroxine doses were re-evaluated in 2011. Results: A total of 125 questionnaires (72%) were returned. ...

Factors associated with parietal cell autoantibodies in the general population

The presence in serum of parietal cell autoantibodies (PCA) is a characteristic of autoimmune gastritis. We determined the prevalence of PCA in the general population and investigate their association with type 2 diabetes, insulin resistance and lifestyle factors related with autoimmune gastritis. A cross-sectional study was performed, involving 429 individuals enrolled in a cohort study of the general population of the Canary Islands. All participants underwent physical examination, provided a blood sample and responded to a questionnaire regarding health and lifestyle factors. Serum concentrations of PCA, soluble CD40 ligand (sCD40L), C-peptide and glucose (to determine insulin resistance) were measured. The association of PCA with the other factors was determined with bivariate analysis, and logistic regression models were used to adjust the associations for age and sex. The prevalence of PCA was 7.8% (95% CI=10.3–5.3). The factors associated with PCA were female sex (p=0.032), insulin resistance (p=0.016), menopause (p=0.029) and sCD40L (p=0.019). Alcohol consumption (p=0.006) and smoking (p=0.005) were associated with low prevalences of PCA. After adjustment for age and sex, the association with PCA was confirmed for smoking (OR=0.1 [0.0–0.9]), alcohol consumption (OR=0.3 [0.1–0.9]), insulin resistance (OR=2.4 [1.1–4.9]), female sex (OR=2.4 [1.1–5.3]), sCD40L (OR=3.7 [1.2–11.4]) and menopause (OR=5.3 [1.2–23.3]). In conclusion, smoking and alcohol consumption acted as protective factors against the appearance of PCA in the general population, whereas female sex, menopause, insulin resistance and elevated serum sCD40L were risk markers for PCA. In patients who smoke or drink alcohol, clinicians should be cautious when using PCA to rule out autoimmune gastritis.

Levels of holo-transcobalamin are more closely associated with pernicious anaemia than total B12 levels

<h3>Aims</h3> Vitamin B12 deficiency is usually due to dietary factors, however clinicians always consider the possibility of autoimmune pernicious anaemia. The Schillings test is no longer routinely available and therefore diagnosis often includes the specific intrinsic factor auto-antibodies (IFAb) +/– parietal cell auto-antibodies (PCAb). Holo-transcobalamin (HoloTC), also known as active B12, has proved to be a more reliable indicator of B12 deficiency than measuring total B12 (TB12). We therefore reviewed our experience with this test to see if HoloTC was more closely associated with pernicious anaemia testing. <h3>Methods</h3> We reviewed 1359 patients where HoloTC +/– TB12 was measured as well as one or more of IFAb and PCAb. We used each patient's first B12 result(s) for the analysis. HoloTC was measured by Abbott AxSym and total B12 was measured by Abbott Architect. PCAb antibodies are detected by immunofluor-escence whereas IFAb are measured by Alegria automated ELISA. <h3>Results</h3> When HoloTC was very low (<10pmol/L), 21% of patients had positive IFAb and 42% had positive PCAb. When HoloTC was mildly low (10–22pmol/L), 8% had positive IFAb and 18% had positive PCAb. For very low TB12 (<100pmol/L), 8% had positive IFAb and 24% had positive PCAb. When TB12 was mildly low (100–149pmol/L), 4% had positive IFAb and 11% had positive PCAb. <h3>Conclusions</h3> PCAb were more likely to be positive at any B12 level consistent with its known poor specificity. The more specific IFAb positivity is more likely to be associated with low HoloTC levels than low TB12 levels.