Anti-parietal Cell Antibodies Research Articles

Predictive Value of Gastrin Levels for the Diagnosis of Gastric Enterochromaffin-Like Cell Hyperplasia in Patients with Hashimoto's Thyroiditis

Aim: Gastrin and chromogranin A (CgA) levels have been tested for the diagnosis of enterochromaffin-like cell hyperplasia (ECLH) in patients with type 1 diabetes and autoimmune atrophic gastritis but not for patients with Hashimoto's thyroiditis (HT). The aim of the study was to develop receiver operating characteristic (ROC) curves for gastrin and CgA levels and other clinical and biochemical parameters, as means for pretest probability of gastric ECLH in patients with HT. Methods: A total of 115 patients with HT were prospectively studied for a median period of 4 (2-7) years. Gastrin, CgA, vitamin B₁₂, anti-parietal cell antibodies, free thyroxine, thyrotropin, and neuron-specific enolase levels were measured. Their predictive values were calculated according to the histological findings for ECLH diagnosis from esophagogastroduodenoscopy-obtained biopsies. Results: Thirteen patients (11.3%) had ECLH. The areas under the curve for gastrin and CgA level were 0.898 (p < 0.001) and 0.853 (p < 0.001), respectively. The product sensitivity × specificity was 0.803 and 0.653 for gastrin and CgA levels >89.5 and >89.1 ng/ml, respectively. Two and 4 patients with ECLH had normal gastrin and CgA levels, respectively. The most specific combined parameters predicting ECLH were gastrin >89.5 ng/ml with concomitant low B₁₂ levels (96.1% specificity). Conclusion: Gastrin levels have high diagnostic accuracy for ECLH identification in patients with HT, and are highly specific when combined with low B₁₂ levels. However, they should be interpreted with caution, as some patients may harbor gastric ECLH even if gastrin levels are not increased, necessitating further follow-up.

Refractory Iron-deficiency Anemia and Autoimmune Atrophic Gastritis in Pediatric Age Group

Refractory iron-deficiency anemia with no obvious etiology in pediatric age can be a puzzling problem. Screening of iron malabsorption conditions, including autoimmune atrophic gastritis (AAG), is emerging as a priority in the investigational procedure. Retrospective analysis of clinical process of children/adolescents with the diagnosis of AAG. Eight patients (aged between 4.7 and 18 years old) were identified. The diagnosis was triggered on the basis of high serum gastrin levels and strong positivity of antiparietal cell antibodies. Upper endoscopy and biopsy revealed atrophic gastritis in all patients, with 2 of them with intestinal metaplasia. Four patients presented with Helicobacter pylori infection object of eradication therapy. After a medium follow-up of 36.6 months, antiparietal cell antibodies and hypergastrinemia did not show evidence of regression. Of the 3 patients who underwent endoscopic reevaluation, a similar anatomo-pathologic pattern was observed in 2 and intestinal metaplasia in 1 patient. Normalization of hematological parameters was achieved, using alternative iron formulas. AAG must be recognized as a pathology affecting pediatric patients. Gastric autoimmune lesion is a chronic process with potential evolution to malignancy. Management guidelines in childhood are not available. Their elaboration is important considering an important risk factor in these age group: a long life expectancy.

Inherited and Secondary Thrombophilia

Case Presentation 1: A healthy 19-year-old man presented with new chest pain and near syncope. Computed tomography pulmonary angiography showed a saddle pulmonary embolus. The patient denied recent travel, trauma, surgery, or hospitalization. His mother had 2 miscarriages at 10 weeks of gestation, and his maternal grandfather had deep venous thrombosis at 60 years of age. Case Presentation 2: A healthy 45-year-old woman reported new dyspnea and left calf pain. Computed tomography pulmonary angiography and compression venous duplex ultrasonography showed bilateral pulmonary emboli and acute left leg deep vein thrombosis, respectively. The patient denied exogenous hormone use, recent travel, trauma, surgery, or hospitalization. Her health maintenance was current, and she gave a family history of pernicious anemia, Grave disease, and amyotrophic lateral sclerosis. Laboratory analyses showed reduced hemoglobin (11.4 g/dL; normal, 12.0–15.5 g/dL), increased red blood cell distribution width (18.9%; normal, 11.9%–15.5%), and mild thrombocytopenia. Neither patient had previous venous thromboembolism, and both were referred to the Mayo Clinic Thrombophilia Center for apparent idiopathic venous thromboembolism. Thrombophilia is defined as a predisposition (susceptibility) to thrombosis. Thrombophilia is not a disease per se, but may be associated with a disease (eg, cancer), drug exposure (eg, oral contraceptives) or condition (eg, pregnancy or postpartum, secondary thrombophilia; Table 1), and thrombophilia may be inherited (Table 2).1 This concept is important because disease susceptibility does not imply an absolute requirement for primary or secondary prevention, or for treatment. Most persons with a thrombophilia do not develop thrombosis. Thus, thrombophilia must be considered in the context of other risk factors for incident thrombosis, or predictors of recurrent thrombosis, when estimating the need for primary or secondary prophylaxis, respectively. View this table: Table 1. Secondary Thrombophilia1 View this table: Table 2. Inherited Thrombophilia1 The role of special coagulation testing for an acquired or inherited thrombophilia is controversial. Thrombophilia testing should only be done if …

Hepatosplenomegaly and pernicious anaemia.

Sir, Pernicious anaemia (PA) is the end stage of atrophic gastritis which results in the loss of parietal cells in the fundus and body of the stomach. Loss of parietal cells is associated with the failure of intrinsic factor production and results in vitamin B12 deficiency and megaloblastic anaemia. Only two cases of splenomegaly coexisting with PA have been reported, but both splenomegaly and hepatomegaly has not been reported yet [1,2]. In this report, we aimed to describe a patient with hepatosplenomegaly due to PA. To the best of our knowledge this is the first documented case of hepatosplenomegaly due to PA and totally resolved by vitamin B12 therapy. A 20-year-old male patient was admitted to our hospital with the complaints of fatigue, weakness, anorexia and palpitation. His complaints had been continued for the past one month. He had no history of another disease or medication. Pallor, subikterus, 3/6 systolic murmur in all valves, palpable splenomegaly at 4 cm below the left costal margin and palpable hepatomegaly 2 cm below the right costal margin were detected on the physical examination. Laboratory examinations revealed the following: LDH: 8440 U/L, AST: 91 U/L, ALT: 45 U/L, total bilirubin: 2.8 mg/dL, indirect bilirubin mg/dL: 2.14, Hgb: 3.9 g/dL, Hct: 12.3%, Wbc: 1400 /uL, Plt: 22000 /uL, MCV: 96 fL, corrected retikulocyte count: 0.25%, direct coombs (-), indirect coombs (-).Hepatitis markers were normal. Hepatosplenomegaly was confirmed using abdominal ultrasonography; the longitudinal spleen size was 182 mm and the craniocaudal liver size was 160 mm, and were found to be increased. The peripheral blood smear contained oval macrocytes, hypersegmented neutrophils, trombocytopenia, leucopenia and low reticulocyte count. Leukemia blasts or atypical cells were not seen on marrow aspiration and biopsy, thus hemolytic anaemia and leukemia were excluded from the differential diagnosis. Bone marrow biopsy was compatible with megaloblastic anaemia. To find the cause of megaloblastic anaemia, the level of vitamin B12 was found 30 pg/mL (197-886 pg/mL), and folic acid level was found in normal ranges. Atrophic gastritis was revealed by gastroscopy and verified in pathological examination. Anti parietal cell antibody was detected positive in blood test. There was no other endocrinopathy accompanying to B12 deficiency; TSH, cortisol, antiadrenal antibody and antithyroid peroxidase levels were found to be normal. Patient was diagnosed as pernicious anaemia due to atrophic gastritis and was given parenteral vitamin B12 treatment. Reticulocyte crisis was seen on the 5th day and leukocyte, hemoglobin, platelet levels were increased on the 3rd week of the treatment without transfusion. In the second month of the treatment there was no hepatosplenomegaly at ultrasonographic scan. The patient has no complaints during the one year follow-up while being monitored from the outpatient clinic. Even though severely anaemic patient with PA may have spleno- megaly, hepatosplenomegaly co-existing with pernicious anaemia is not considered to be a characteristic feature of PA, [1,2]. PA should be kept in mind in the differential diagnosis of hepatosplenomegaly like in our patient. According to the literature the relationship between PA and splenomegaly has been well established, but hepatomegaly of this association has not been mentioned. In our opinion, it might be resulted from extramedullary hematopoiesis, because hepatomegaly was regressed after the treatment of severe anaemia by vitamin B12. Plasma B12 levels, gastroscopy, peripheral blood smear, bone marrow biopsy should be considered, especially in pancytopenic patients with hepatosplenomegaly.

Are patients with autoimmune thyroid disease and autoimmune gastritis at risk of gastric neuroendocrine neoplasms type 1?

The aim of this study was to investigate the prevalence of autoimmune gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid disease. Prospective observational study in a single institutional study. One hundred and twenty patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Unit. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up of 37·5 ± 14·4 months. Autoimmune gastritis was defined by the presence of antiparietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin Α were also measured. One hundred and eleven patients had Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin Α; Helicobacter pylori infection was histologically identified in 15 of 40 (37·5%) patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7 of 40 (17·5%)]. Only increased gastrin (P = 0·03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up. Concomitant autoimmune gastritis was found in 33·3% of patients with autoimmune thyroid disease, 17·5% of whom had ECL-cell hyperplasia that evolved to GNEN1 in one (2·5%). Larger studies with longer follow-up are needed to define the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications.

A 67-year-old man with cognitive decline incidentally diagnosed with gastric submucosal tumor

Introduction.–Vitamin B12 deficiency can lead tomemory loss, disorientation and dementia is well known from the past. Therefore when we first meet the patient who have cognitive decline, we must check the Vitamin B12 level. Methods and results.– A 67-year-old man visited our clinic with cognitive decline. He had no specific past history of illness. Two years ago, memory complaint was started. His neuropsychological test showed both frontal and left temporal lobe dysfunction. His educationwas 16years. Korean-MiniMental State Examination (KMMSE) score was 26 and Clinical Dementia Rating (CDR) score was 0.5. And sum of box score was 4. He was in mild dementia state. The routine lab tests revealed that he had vitamin B12 deficiency. Vitamin B12 level was 45pg/mL and homocysteinwas 83.8umol/L. His hemogoblin was 13.3 g/dL. Antiparietal cell antibody(Ab) was positive and anti intrinsic factor Abwas negative. Gastrin level was increased. Under the esophagogastroduodenoscopy, there was no evidence of atrophic gastritis but gastric submucosal tumor was found. If the autoimmune gastritis was in chronic state, atrophic gastritismight be found. Usually after chronic stage of autoimmune gastritis, gastric cell dysplasia and submucosal tumor can occur. But in this case, there was no anemia and no atrophic gastritis. It suggests his hypovitaminosis B12 state has not been that long. Conclusions.– Whether his submucosal tumor was due to autoimmune gastritis or incidental growth, it was a unique case who did not have pernicious anemia and atrophic gastritis have a gastric submucosal tumor.

Anti-parietal cell antibodies and pernicious anemia in patients with type 1 diabetes mellitus and multiethnic background

Anti-parietal cell (APC) antibodies and pernicious anemia (PA) were evaluated in patients with type 1 diabetes (n=75) and in controls. A higher frequency of APC (13.3%) and PA (4%) was found in cases than in controls (p=0.003), associated with other autoimmune diseases (p=0.003), but not with insulin or PTPN22 polymorphisms.

PELIOSIS HEPATIS IN A PATIENT WITH COELIAC DISEASE AND ON ORAL CONTRACEPTIVE PILL: A CASE REPORT

IntroductionPeliosis hepatis (PH) is a rare vascular condition which can be seen in a variety of settings. It is characterized by the presence of cystic blood-filled cavities distributed throughout the...

Association between vitamin B12 level and anti-parietal cells and anti-intrinsic factor antibodies among adult Jordanian patients with Helicobacter pylori infection

ObjectiveEvaluate the association of Helicobacter pylori infection with anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) and their impact on vitamin B12 serum level. Patients and methodsOne hundred patients (M/F: 43/57; age 46.5±17.5 years) who underwent upper gastrointestinal endoscopy at King Abdullah University Hospital, Irbid, Jordan were enrolled in the study. The patients were grouped as H. pylori-infected (n=81) or H. pylori negative (n=19) by histopathological examination. Fasting serum vitamin B12 levels, anti-parietal cell antibodies and anti-intrinsic factor antibodies for patients and controls were determined. ResultsAnti-parietal cell antibodies and anti-intrinsic factor antibodies were positive in 9.9% and 18.5% of H. pylori-positive patients respectively. None of the H. pylori negative subjects had anti-parietal cell antibodies or anti-intrinsic factor antibodies. Serum vitamin B12 level was lower in the H. pylori-infected patients (275±70.4pg/mL) than in controls (322.9±60.7pg/mL; p<0.05). H. pylori was positive in 94% of the low-vitamin B12 group compared with 64.6% of the normal-vitamin B12 group (p<0.5). ConclusionPatients with H. pylori infection are more likely to have anti-parietal cell antibodies and anti-intrinsic factor antibodies. There was an association between H. pylori infection and lower vitamin B12 levels. H. pylori infection might be a significant factor in the pathogenesis of autoimmune gastritis.

Xanthomatous hypophysitis as a cause of cluster headache: a case report

Our case: We report a 23-year-old man with XH who presented with cluster type headache, diabetes insipidus and MRI-proven pituitary intrasellar mass. Since 2009 our patient suffered from recurrent headache. CT scan, ophthalmological, neurological investigations revealed no obvious cause of the symptoms. In April 2011, polyuria-polydipsia occurred and endrocrine investigations revealed diabetes insipidus. Anterior pituitary hormone levels were normal: TSH: 1.3 mIU/l, FSH: 2.4 IU/l, LH: 3.7 IU/l, PR L: 197 mIU/l, ACTH: 7.78 pm/l, cortisol 08 h: 444 nm/l. After initialization of ddAVP treatment, diuresis returned to normal. The pituitary MRI scan revealed a 14x10x17 mm inhomogenous lesion with the disappearance of the hyperintense signal of the neurohypophysis. In July 2011, transsphenoideal surgery was performed and histology proved xanthomatous hypophysitis. We could stop the glucocorticoid (GC) treatment without having any perioperative complication. The headache resolved but the diabetes insipidus persisted. The anterior pituitary function after the surgery was normal: serum cortisol 08 h: 404-445 nm/l, ACTH:6.49 pm/l, FSH:3.1 mIU/l, LH:4.2 mIU/l, TSH:1.61 mIU/l. 2 months later severe cluster type headache occurred. Endocrine investigations revealed hypadrenia, hypothyroidism and peripheral hypogonadism: serum cortisol 08 h: 96 nm/l, TSH: 1.32 mIU/l, ft4: 10.5 pm/l, testosterone: 3.44 nm/l, FSH: 3.3 mIU/l, LH: 2.8 mIU/l, ACTH: 3.38pm/l. LHRH test results: FSH: 0 min: 2.8, 30 min: 4.7, 60 min: 5.1 mIU/l, LH: 0 min: 2.9, 30 min:13.5, 60 min:13.8 mIU/l. The postopreative pituitary MRI scan proved the persistent presence of the inhomogenous mass. After initialization of glucocorticoid replacement the headache disappeared. With levothyroxin, testosterone supplementation and gradually lowered dosage of GC and all symptomps disappeared with the exception of diabetes insipidus. Despite of low IGF 1 (92 ng/ml,age matched reference rate:117-329 ng/ml) and hGH (0.08 ng/ml) levels GH therapy was not introduced. Autoimmune screen: ANA, antiCL, antib2GP, antitransglutaminase, antiTPO and antiparietal cell antibody was negative. Regularly performed sella MRI scans showed no change in tumor size and appearance after the surgery and after the introduction of hormone replacement therapy. The patient requires GC supplementation only in case of recurrent cluster type headache, but no persistent replacement is needed. Conclusion: Typical cluster type headache and diabetes insipidus were the two main syndromes of the XH In our case. The patient requires GC supplementation only in case of recurrent cluster type headache, but no persistent replacement is needed. The cause of the XH is still unknown, but the regular endocrine check-up can reveal disturbances in the pituitary function and, as in our case, glucocorticoid replacement seems to be effective in the treatment of the disease. ABSTRACT Introduction: Hypophysitis is an inflammatory disease of the pituitary gland that may mimic pituitary tumors clinically and radiologically. Primary hypophysitis has traditionally been classified as lymphocytic (LH), granulomatous (GH), and xanthomatous (XH). Case description: We report on a case of a xanthomatous hypophysitis initially diagnosed as pituitary adenoma. A 23-year-old men suffered from typical cluster type headache. Two years after the first symptoms, we confirmed diabetes insipidus. All the anterior pituitary hormone levels were normal. Sella MRI scan depicted a 14x10x17 mm inhomogenous mass. Transphenoidal surgery was performed; the removed tissue showed accumulation of foamy cells and xanthomatous epithelioid cells. Following an uneventful postoperative recovery, severe cluster type headache returned after stopping the hydrocortisone therapy. The endrocrine work-up revealed hypadrenia (morning cortisol: 96 nm/l, ACTH:3.38 pm/l), hypothyroidism ( ft4:10.5 pm/l), hypogonadism (testosterone: 3.44 nm/l) with normal FSH and LH (FSH:3,3 mIU/l,LH:2,8 mIU/l). We restarted hormonal therapy: hydrocortisone, levothyroxine and testosterone were stepwise reintroduced. During the followup period we could stop the hydrocortisone and levothyroxine supplementations, whereas the patient has permanently required desmopressin and testosterone substitution. Control sella MRI scans revealed no progression of the intitially seen pituitary mass. Conclusion: We describe an unusual case of xanthomatous hypophysitis causing cluster type headache and permanenty requiring ddAVP (desmopressine) and testosterone supplementation without requiring maintenance medication with hydrocortisone and levothyroxin.

Hepatitis C virus antibody positivity may not be associated with hepatitis C infection in patients with autoimmune gastritis

Autoimmune gastritis (AIG) is an organ-specific autoimmune and inflammatory condition that manifests itself by loss of gastric parietal cells. It is usually clinically silent in the early stages of the disease, and demonstrable by the formation of antibodies against parietal cells and/or intrinsic factor 1. Patients infected with hepatitis C virus (HCV) frequently have antibodies and various autoimmune diseases 2–4. The relationship between HCV and extrahepatic manifestations is well established 5. Our recent observation that some of the patients with AIG have HCV antibodies (anti-HCV) has led us to investigate the prevalence of anti-HCV positivity and associated factors in patients with AIG 6. We evaluated 104 patients with AIG by HCV serology and compared them with 108 patients who were referred for gastrointestinal endoscopy. Patients with existing liver disease, esophageal varices noted during endoscopy, a history of previous surgery, and blood transfusion were excluded from the study. Anti-HCV was measured by an enzyme-linked immunoassay (Abbott Laboratories, Chicago, Illinois, USA). Four of the patients with AIG were positive for anti-HCV; however, none of the individuals from the control group were positive for anti-HCV (4/104 vs. 0/108, P=0.04). Four patients who were anti-HCV positive were tested with HCV-RNA (Roche Diagnostics, Basel, Switzerland) and were found to be negative. The demographic and clinical characteristics of these four patients are shown in Table 1. All of these four patients were positive for antiparietal cell antibody (APCA); one of them had concurrent autoimmune thyroid disease. Logistic regression analysis showed that sex (P=0.055), age (P=0.360), APCA positivity (P=0.149), anti-Helicobacter IgG (P=0.906), and serum gastrin level (0.484) were not significant risk factors for anti-HCV positivity.Table 1: Demographic and clinical parameters of anti-hepatitis C virus positive patientsGastric autoimmune diseases have been analyzed extensively in 189 patients with chronic hepatitis C infection before, during, and after interferon-α therapy by Fabbri et al.7. They found APCA positivity and three-fold gastrin levels in three and nine patients at baseline, in 25 and 31 patients after interferon-α therapy, and in seven and 14 patients 12 months after withdrawal. They reported that the development of AIG was associated with the prevalence of autoimmune thyroiditis and concluded that interferon therapy was closely associated with the occurrence of AIG especially in female patients. Our study approached this issue from another point of view by investigating the existence of anti-HCV in patients with AIG. As AIG is an autoimmune disease, autoimmunity may play a role in the development of false-positive anti-HCV test results. Another explanation for the false-positive test results may be associated with the test used. Ali and Lal 8 investigated 254 anti-HCV-positive patients and they found viremia in 211 patients; the remaining 43 (16.9%) patients were false positive. In conclusion, physicians managing patients with AIG should keep in mind that anti-HCV positivity may exist in some of the patients with AIG and this condition is not always associated with HCV infection, considering patients’ fears and concerns about having a serious infection. Acknowledgements Conflicts of interest There are no conflicts of interest.

Diffuse Nodular Lymphoid Hyperplasia of Intestine in Selective IgG 2 Subclass Deficiency, Autoimunne Thyroiditis, and Autoimmune Hemolytic Anemia in 60 Year Old Male

Purpose: Diffuse Nodular Lymphoid Hyperplasia (DNLH) of the intestine is a rare lymphoproliferative disorder of uncertain etiology. We present a rare case of DNLH associated with IgG2 subclass deficiency, autoimmune thyroiditis and autoimmune hemolytic anemia. A 60 year old Turkish male presented to GI clinic with watery diarrhea and crampy abdominal pain for 1 month. He had a history of treated prostate cancer. He denied any family history, alcohol, tobacco, or illicit drugs. He denied any sick contacts, or recent travel. One week prior, he was seen in the ER for similar complaints where he was anemic (hemoglobin 7.4 g/dl, mean corpuscular volume 103). CT abdomen revealed extensive lymphadenopathy. He was discharged with a one week course of ciprofloxacin and metronidazole, and scheduled for follow up in the GI clinic. At follow up iron deficiency anemia was found. Assays for vitamin B12, folate, methylmalonic acid and homocysteine were within normal range. Lactate dehydrogenase and reticulocyte count was high, haptoglobin low, and direct coomb's test positive with warm antibody. Gastrointestinal bacterial and parasitic infections were ruled out. Tissue transglumatinase antibody IgA and anti-parietal cell antibody were negative. Thyroid stimulating hormone was 12.6, with elevated thyroglobulin and thyroid peroxidase antibody. EGD and colonoscopy showed nodular mucosa in duodenal bulb and rectosigmoid respectively. Small bowel series followed by capsule endoscopy was performed. Bone marrow and abdominal lymph node biopsy was negative for malignancy. Gallium scan was negative for any metastatic disease. An increased risk (2-10%) of malignancy, mainly gastrointestinal lymphoma has been reported in patients with DNLH and hypogammaglobulinemia. These lymphoid aggregates could be an independent response to antigenic stimuli in presence of deranged immunoglobulin function. However, the relationship is unclear. Because of the risk of malignant transformation prophylactic examinations and small bowel studies are recommended by some authors. Diffuse nodular lymphoid hyperplasia in itself is a rare benign condition of unknown etiology. In symptomatic patients, workup should be directed towards underlying hypogammaglulinemia, infections and possible malignancy. Eradication of infection could lead to resolution of symptoms. Patients should undergo prophylactic surveillance endoscopy to rule out complications and to establish extent of disease. However, there are no clear cut guidelines for surveillance.

GADA Titer-Related Risk for Organ-Specific Autoimmunity in LADA Subjects Subdivided according to Gender (NIRAD Study 6)

Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects. Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001). In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender.

Clinical Profiles, Endoscopic and Laboratory Features and Associated Factors in Patients with Autoimmune Gastritis

Background/Aims: Autoimmune gastritis (AIG) may predispose to gastric carcinoid tumors or adenocarcinomas and may also cause unexplained iron and/or vitamin B₁₂ deficiency. The aims of this study were to explore clinical manifestations, endoscopic findings and laboratory features of patients with AIG. Methods: 109 patients with AIG were enrolled into the study. In addition to demographic and clinical data, gastric lesions, serum gastrin, vitamin B₁₂, antiparietal cell antibody (APA), current Helicobacter pylori status, and anti-H. pylori IgG were also investigated. Results: The mean age of the patients was 53.06 ± 12.7 years (range 24–81; 72 (66.1%) women). The most common main presenting symptom was abdominal symptoms in 51 patients, consultation for iron and/or vitamin B₁₂ deficiency in 36, and non-specific symptoms including intermittent diarrhea in 15 patients. Endoscopic lesions were detected in 17 patients, hyperplastic polyps in 8, gastric carcinoid tumor in 4, fundic gland polyps in 3, and adenomatous polyps in 2 patients. H. pylori was negative in all patients in biopsy specimens; however, anti-H. pylori IgG was positive in 30 (27.5%) patients. 91 patients (83.4%) were positive for APA. Conclusion: In patients with AIG, the main symptoms prompted for clinical investigation were: abdominal symptoms, iron/B₁₂ deficiency and non-specific symptoms. 20% of patients with AIG had various gastric lesions including type I gastric carcinoids. None of the patients were positive for H. pylori by means of invasive tests; however, anti-H. pylori IgG was found in 27.5% of patients. Patients referring with non-specific abdominal symptoms such as bloating, diarrhea and iron/B₁₂ deficiency should be investigated for the presence of AIG.

Etiology of anemia in primary hypothyroid subjects in a tertiary care center in Eastern India

Introduction:The association of anemia with primary hypothyroidism has been common knowledge for many years. However; its pathogenesis is far from clear in many cases. Often the causes of anemia are manifold.Aims and objectives:In this study, we evaluated the causes of anemia in patients with primary hypothyroidism.Materials and Methods:Sixty adult nonpregnant untreated primary hypothyroid patients with anemia without any obvious cause were included. All patients were subjected to full medical history, clinical examination, biochemical and imaging studies. Serum iron profile, vitamin B12, folic acid, anti parietal cell antibody, anti TPO antibody, bone marrow study, and stool for occult blood, Coomb's test, HPLC for hemoglobinopathies and complete hemogram with reticulocyte count were done and analyzed.Results:Normocytic, normochromic anemia was present in 31 patients (51.6%) followed by microcytic anemia in 26 patients (43.3%). Six patients (10%) had megaloblastic anemia with vitamin B12 deficiency including 3 cases of pernicious anemia. Two patients had combined deficiency of iron and vitamin B12.Conclusion:Normocytic normochromic anemia with normal bone marrow was commonest type of anemia in this study, followed by iron deficiency anemia.

Gastrointestinal and Hepatic Manifestations of Sjogren Syndrome

Sjogren syndrome (SS) is an autoimmune disease that affects exocrine glands and therefore may affect the gastrointestinal system, from the mouth, esophagus, and bowel to the liver and pancreas. Oral involvement in SS is mainly characterized by dryness, with a wide spectrum of symptoms, from mild-to-severe xerostomia with dysgeusia and tooth decay. The dysphagia, although common, does not correlate with the reduced salivary flow rate or the dysmotility that may be present. Dyspepsia, found in up to 23% of patients, may be associated with gastritis, reduced acid production, and antiparietal cell antibodies, but rarely pernicious anemia. Pancreatic involvement, although rare, includes pancreatitis and pancreatic insufficiency. The most common causes of liver disease are primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatitis C virus (HCV). Although abnormal liver tests are found in up to 49% of patients, they are usually mild. Although sicca syndrome, abnormal histology of the salivary glands, and abnormal sialograms are common in primary biliary cirrhosis, the antibodies to Ro/SSA or La/SSB antigens are infrequent. Xerostomia, sialadenitis, abnormal salivary flow rates, and abnormal Schirmer test in HCV vary widely among the studies, although the antibodies to Ro/SSA or La/SSB are only 1%. Several studies show that HCV is in saliva, although how this may impact sicca syndrome or SS in HCV is unclear. SS as a disease of exocrine glands affects many parts of the gastrointestinal system.

When are laboratory tests indicated in patients with vitiligo?

Background: Vitiligo has been associated with multiple endocrine and immune conditions. Several laboratory tests have been assessed in this disease with controversial results. Objective: The aim of this study is to analyze the levels autoantibodies, basal glycaemia, vitamin B12, folic acid and thyroid function and its association with the diagnosis and outcome of vitiligo patients through a case-control study. Material and methods: This case-control study was performed on 196 consecutive patients with vitiligo referred to our Dermatology Department. As a control group, 160 healthy individuals without vitiligo or known history of immunologic/endocrine disease were included. Data were analyzed using the SPSS 17.0 statistical software package. Results: Clinical, analytical and demographic data have been recorded. Our results showed that anti-thyroid peroxidase antibody and anti-parietal gastric cell antibody could be useful laboratory markers in a subpopulation of vitiligo patients. However, testing anti-nuclear antibody, anti-thyroglobulin antibody, folic acid and vitamin B12 seems to have limited clinical implication and diagnostic relevance in our routine clinical practice. Limitations: This study addressed a selected population of vitiligo patients in Spain and may not generalize to different clinical settings or regions. The study of a wider sample would confirm these findings and allow a detailed analysis of the above factors as a function of the clinical subtype of vitiligo. Conclusion: We have determined the more efficient serological markers to order in vitiligo patients. Our findings suggest that anti-thyroid peroxidase antibody and anti-parietal gastric cell could be useful tests for the characterization of specific subpopulations of vitiligo patients in terms of severity and co-morbidity, so their determination could have a prognostic value.

Three Different Presentation of Same Pathophysiology

We report three male patients of younger age group presented with acute vein thrombosis of different sites, right lower limb, cortical venous sinuses thrombosis with cerebral vascular accident and third case is mesenteric vein thrombosis. All patients were Vegetarian, had low level of cobalamin with marked hyper homocysteinemia with normal serum and red cell folic acid. The low Cobalamin level was not suspected secondary to pernicious anemia, based on the fact that there was no evidence of atrophic gastritis and an absence of antiparietal cell antibodies. There were no evident of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, and hormone replacement therapy. No deficiencies in protein C, protein S, or antithrombin III, normal factor V Leiden, no prothrombin gene mutation 20210A and no clone for paroxysmal nocturnal hemoglobin-urea were detected, no cause was found for the thrombosis apart from their secondary hyperhomocysteinemia.

Myotonic dystrophy type 2 and autoimmune chronic gastritis: an incidental association?

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystem disease caused by a large expansion of a CCTG repeat located in intron 1 of the zinc finger protein 9 (ZNF9) gene on the chromosome 3q21.3. The clinical picture of DM2 shows similarities to as well as differences from myotonic dystrophy type 1 (DM1). DM2 is mainly characterized by myotonia, muscle dysfunction including weakness, myalgia and stiffness, cataracts, cardiac arrhythmia and endocrine disturbances [1]. A recent study found a significantly higher frequency of autoimmune disease and autoantibodies in DM2 patients compared with DM1 subjects and the general population, suggesting a strong association between DM2 and autoimmunity [2]. A 48-year-old Italian woman was recently referred to us with a 4 year history of fluctuating muscle weakness, pain and stiffness of lower limbs. Her past history revealed chronic immune thrombocytopenia (ITP), Hashimoto’s thyroiditis (HT) and mammary cancer. Family history disclosed cardiopathy, myalgias and stiffness in the paternal members. No history of autoimmune disorders was referred in the family members. On admission, neurological examination showed grip myotonia, slight weakness (MRC grade 4) of neck flexors and proximal lower limbs muscles. Routine blood analysis confirmed thrombocytopenia and uncovered mild hyperCKemia (265 U/L; normal 10–170 U/L). Electromyography showed myotonic discharges in both the proximal and distal muscles of the upper and lower limbs. Ophthalmological evaluation revealed initial cataracts. Electrocardiographic and echocardiographic examination excluded conduction abnormalities and cardiomyopathy, respectively. Molecular analysis of dystrophia myotonica protein kinase (DMPK) gene did not reveal CTG repeat expansion. Muscle biopsy (vastus lateralis) showed fiber size variability, increased internal nuclei, frequent nuclear clumps and the evidence of type 2 fiber atrophy. Fluorescence in situ hybridization using (CAGG)5 probe was performed on skeletal muscle sections: the presence of nuclear accumulation of CCUG-containing RNA confirmed the clinical diagnosis of DM2. Serum autoantibody assessment showed the elevated levels of anti-thyroglobulin and antithyroperoxidase antibodies and uncovered high titers of antiparietal cell antibodies (82.8 U/mL; normal \10 U/mL). Thus, we performed esophagogastroduodenoscopy and gastric biopsies which revealed chronic gastritis with intestinal metaplasia, mild gastric atrophy and foveolar hyperplasia, primarily affecting the body/fundus of the stomach. Moreover, further biochemical analysis showed hypergastrinemia (345 pg/mL; normal \108 pg/mL) and vitamin B12 deficiency (103 pg/mL; normal 140–900 pg/mL). However, both anemia and gastrointestinal symptoms were absent. On the basis of laboratory and histopathological findings, a diagnosis of subclinical autoimmune chronic gastritis (ACG) was established. Our case report expands the spectrum of autoimmune disorders in DM2 and further suggests a strong association F. Sicurelli (&) A. Mignarri A. Carluccio D. Marino A. Federico M. T. Dotti Neurology and Neurometabolic Unit, Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy e-mail: francesco.sicurelli@gmail.com

Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4(+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.