Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pernicious anaemia (PA) and chronic atrophic gastritis (CAG) aggregate in families, occur more often in women, and are associated with various heritable traits such as fair skin and blue eyes. They are linked to certain HLA types. Linkages are relatively weak for A and B antigens, but somewhat stronger in the case of DR antigens. There are strong associations between PA and other organ-specific autoimmune diseases, particularly those affecting the thyroid. Discordance for PA in monozygotic twins has been reported, and it may well be that expression of the disease requires, in a genetically susceptible individual, initial injury to the gastric mucosa by some environmental agent such as a virus or some physical irritant, with perpetuation of injury then depending upon autoimmune mechanisms. Numbers of T cells are substantially increased in the gastric mucosa of patients with PA, but the ratio of T suppressor to T helper cells is normal. There is a relatively greater increase in numbers of cells not of T lineage, presumably B-cells. Gastric autoantibodies, both to different components of the parietal cell and to two sites on the IF molecule, are present in a majority of patients with PA. There is evidence that these autoantibodies, especially PCA, may be cytotoxic to parietal cells, and may also inhibit their maturation and proliferation. Antibodies to chief cells have not been described, and the parallel disappearance of these cells in atrophic gastritis is unexplained. The peripheral blood lymphocytes of some patients with autoimmune gastritis transform, or produce lymphokines, when exposed to gastric antigens, and patients with PA have been shown to have delayed type cutaneous hypersensitivity to gastric antigens. The relevance of these observations to the pathogenesis of their gastric mucosal lesion is unclear. There is a growing body of evidence to support the operation of humoral immune mechanisms in autoimmune gastritis, but this clearly does not preclude the coexistent involvement of cellular mechanisms. For example, impaired suppressor T cell function has been strongly implicated in certain other autoimmune disorders, but has received scant attention in PA. By generally accepted criteria, PA is an excellent example of an organ-specific autoimmune disease. As yet, there is no acceptable single unifying hypothesis which will account for all of the phenomena which have been described in the disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunological aspects of gastritis and pernicious anaemia. 332 29

The frequency and significance of gastric parietal cell autoimmunity was assessed in 771 patients with insulin-dependent diabetes (IDD) of onset before 30 yr of age. Gastric parietal autoantibodies (PCA) were found 4 times more frequently in the patients with IDD (9%) than among 600 matched nondiabetic controls (2%). Caucasian female patients with IDD had PCA twice as frequently as male patients. Thyroid microsomal autoantibodies were more frequent in patients with IDD and PCA, than in those with IDD alone (Caucasian 46% versus 18%, black 25% versus 2.5%). A history of pernicious anemia and/or PCA was found in 25 or 40 families of IDD probands with PCA. Achlorhydria was demonstrated in 6 of 11 patients (54%) with PCA but in none of seven IDD patients without PCA. The six patients with achlorhydria had significantly lower uptakes of oral radiolabeled cobalamin, lower serum cobalamin levels, lower intrinsic factor-R protein ratios in their gastric aspirates, and lower plasma ferritin levels than patients with IDD but without PCA. None of the study group had IF antibodies in their serum or gastric juice. Overt pernicious anemia and neuropathy were found in one patient with PCA. Young patients with IDD at risk for atrophic gastritis and cobalamin deficiency can initially be identified by screening for PCA. Many of these young patients with PCA already have achlorhydria and evidence of decreased absorption of cobalamin. These patients can then be followed with cobalamin levels and/or with complete blood counts to identify those requiring therapy.
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PMID:Predictive value of gastric parietal cell autoantibodies as a marker for gastric and hematologic abnormalities associated with insulin-dependent diabetes. 717 96

Autoimmune type 1 diabetic patients show a high prevalence of thyroid peroxidase (TPO), parietal cell (PCA), anti-adrenal (AAA) and anti-endomysium antibodies (EmA-IgA), which may be accompanied with clinical disease. We studied the grade of associated organ-specific autoimmunity and the pattern of prevalence of TPO and PCA by age, gender, duration, age at onset of diabetes, and HLA DR haplotype in 783 type 1 diabetic patients, consisting of 286 children and 497 adults (M/F: 389/394), with a mean diabetes duration of 11.8 +/- 10.1 years. The relationship between islet cell (ICA), glutamic acid decarboxylase-65 (GADA) and thyro-gastric auto-antibodies was also investigated. TPO were present in 21.6%, PCA in 18.3%, AAA in 2.2% and EmA-IgA in 2.1% of the patients. The presence of TPO is determined by gender (p < 0.0001), age (P = 0.0008), and PCA status (p = 0.029). The presence of PCA is only influenced by age (p = 0.0027) and TPO status (p = 0.0155). Patients with ICA+ > or = 3 years had a higher prevalence of thyro-gastric auto-antibodies (p = 0.045) than ICA- subjects. Also, PCA were more prevalent in GADA+ than GADA- patients (p = 0.005). We observed an association between HLA DR5 and PCA (p = 0.0012). Dysthyroidism was more prevalent in TPO+ than TPO- subjects (p < 0.0001). PCA+ subjects had a higher prevalence of iron deficiency anaemia (p = 0.0099) and pernicious anaemia (p < 0.0001) than PCA- patients. In conclusion, particularly type 1 diabetic patients with persisting ICA > or = 3 years or with GADA, show a high prevalence of thyro-gastric auto-antibodies. Based on antibody-positivity we observed a high prevalence of thyroid disease, iron deficiency anaemia and pernicious anaemia, which can compromise the health of the diabetic patient.
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PMID:[Diabetes mellitus type 1 and associated organ-specific autoimmunity]. 1100 7

The autoimmune attack in type 1 diabetes is not only targeted to beta cells. We assessed the prevalence of thyroid peroxidase (aTPO), parietal cell (PCA), antiadrenal (AAA) and endomysial antibodies (EmA-IgA), and of overt autoimmune disease in type 1 diabetes, in relation to gender, age, duration of disease, age at onset, beta-cell antibody status (ICA, GADA, IA2A) and HLA-DQ type. Sera from 399 type 1 diabetic patients (M/F: 188/211; mean age: 26 +/- 16 years; duration: 9 +/- 8 years) were tested for ICA, PCA, AAA and EmA-IgA by indirect immunofluorescence, and for IA2A (tyrosine phosphatase antibodies), GADA (glutamic acid decarboxylase-65 antibodies) and aTPO by radiobinding assays. The prevalence rates were: GADA 70%; IA2A, 44%; ICA, 39%; aTPO, 22%; PCA, 18%; EmA-IgA, 2%; and AAA, 1%. aTPO status was determined by female gender (beta = - 1.15, P = 0.002), age (beta = 0.02, P = 0.01) and GADA + (beta = 1.06, P = 0.02), but not by HLA-DQ type or IA2A status. Dysthyroidism (P < 0.0001) was more frequent in aTPO + subjects. PCA status was determined by age (beta = 0.03, P = 0.002). We also observed an association between PCA + and GADA + (OR = 1.9, P = 0.049), aTPO + (OR = 1.9, P = 0.04) and HLA DQA1*0501-DQB1*0301 status (OR = 2.4, P = 0.045). Iron deficiency anaemia (OR = 3.0, P = 0.003) and pernicious anaemia (OR = 40, P < 0.0001) were more frequent in PCA + subjects. EmA-IgA + was linked to HLA DQA1*0501-DQB1*0201 + (OR = 7.5, P = 0.039), and coeliac disease was found in three patients. No patient had Addison's disease. In conclusion, GADA but not IA2A indicate the presence of thyrogastric autoimmunity in type 1 diabetes. aTPO have a female preponderance, PCA are weakly associated with HLA DQA1*0501-DQB1*0301 and EmA-IgA + with HLA DQA1*0501-DQB1*0201.
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PMID:Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes. 1170 58

Type 1 diabetes mellitus (T1D) patients (G1; n=73) and first degree relatives with islet cell antibody (ICA) values of >or=10 JDF u twice or >or=20 JDF u one and loss of FPIR (G2; n=18) were screened for two other autoantibodies, anti-glutamic acid decarboxylase (GADA) and insulin autoantibodies (IAA), and for other organ-specific autoantibodies, anti-gastric parietal cell (anti-PCA) and anti-thyroid peroxidase (anti-TPO) as well. The two control groups consisted of healthy subjects (G3; n:55 and G4; n:13). In G1, positivity of ICA, GADA, IAA, anti-TPO and anti-PCA were 63%, 75.1%, 27.4%, 17.8% and 8.2%, respectively. In G2, positivity for GADA, IAA, anti-TPO and anti-PCA were 55.6%, 11.1%, 16.7% and 11.1%, respectively. None of the anti-TPO or anti-PCA positive cases had clinical or laboratory thyroid disease or pernicious anemia. Other organ specific antibodies, in case they accompany GADAand/or IAA in high risk individuals, result in higher risk for T1D. Moreover, this condition may indicate future potential for developing thyrogastric autoimmune diseases. In conclusion; autoantibodies are markers for autoimmune destruction in T1D, and for identification of subjects at risk for disease. Even at the time of diagnosis of T1D, screening for thyrogastric autoimmunity might be recommended for early detection of the relevant diseases.
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PMID:Organ specific autoantibodies in preclinical and early clinical type 1 diabetes in Turkey. 1757 23

Autoantibodies targeting the H+/K+-ATPase proton pump of the gastric parietal cell (parietal cell antibodies [PCA]) are diagnostic of atrophic body gastritis (ABG) leading to pernicious anemia (PA). PCA, ABG, and PA occur in increased frequency in patients with type 1 diabetes and their relatives and are considered "minor" components of forms of autoimmune polyglandular syndrome (APS). A customized radioimmunoprecipitation assay was applied to 6,749 samples from the Type 1 Diabetes Genetics Consortium to measure ATP4A autoreactivity. Autoantibody prevalence was correlated with variants in HLA class II, PTPN22, and CTLA4 genes. With an ATP4A radioimmunoprecipitation assay, PCA were detected in sera from 20.9% of affected individuals. PCA prevalence increased with age and was greater in females (25.3%) than males (16.5%) and among Hispanics (36.3%) and blacks (26.2%) compared with non-Hispanic whites (20.8%) and Asians (16.7%). PCA and other organ-specific autoantibodies GAD65, IA-2, thyroid peroxidase (TPO), 21-hydroxylase (21-OH), and transglutaminase (TG) clustered within families with heritability estimates from 71 to 95%. PCA clustered with TPO, 21-OH, and persistent GAD65 autoantibodies but not with celiac (TG) or IA-2 autoantibodies. PCA-positive subjects showed an increased frequency of DRB1*0404, DPB1*0201, and PTPN22 R620W (rs2476601-T) and a decreased frequency of DRB1*0101, DPB1*0301, and CTLA4 CT60 (rs3087243-T). Genetic variants accounted for 4-5% of the heritable risk for PCA. The same alleles were associated with other autoantibody phenotypes in a consistent pattern. Whereas most of the heritable risk for PCA and other antibodies reflects genetic effects that are tissue specific, parietal cell autoimmunity is a major pathogenetic contributor in APS2.
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PMID:ATPase4A Autoreactivity and Its Association With Autoimmune Phenotypes in the Type 1 Diabetes Genetics Consortium Study. 2640 69