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PubMed1998

IL-12 down-regulates autoantibody production in mercury-induced autoimmunity.

In genetically susceptible H-2s mice, subtoxic doses of mercuric chloride (HgCl2) induce a complex autoimmune syndrome characterized by the production of anti-nucleolar IgG Abs, lymphoproliferation, increased serum levels of IgG1 and IgE Abs, and renal Ig deposits. Mercury-induced autoimmunity in H-2s mice provides a useful model for chemically related autoimmunity in humans. The increase in serum IgG1 and IgE, which are under IL-4 control, suggests a role for the Th2 subset in this syndrome. The IL-12 cytokine induces T cell proliferation and IFN-gamma production and is necessary for differentiation of naive T cells into the Th1 subset. To gain an understanding of T cell control in this syndrome and, in particular, Th1/Th2 regulation, we assessed the effect of IL-12 administration in mercury-induced autoimmunity. Groups of A.SW mice (H-2s) received HgCl2 plus IL-12, HgCl2 alone, or IL-12 alone. IL-12 treatment resulted in a dramatic reduction of the anti-nucleolar Ab titers. IL-12 also inhibited the HgCl2-induced serum IgG1 increase, but, in contrast, did not significantly affect IgE induction in this model. This observation may be related to our unexpected finding that IL-12 further potentiated the HgCl2-triggered IL-4 induction in this model. The levels of renal Ig deposits were similar in mice receiving HgCl2 alone or HgCl2 plus IL-12. Our results indicate that IL-12 can down-regulate the autoimmune component of this experimental syndrome and that the various manifestations of mercury-induced autoimmunity are independently regulated.

Adjuvants, Immunologic↗

PubMed1998

Tissue-specific up-regulation of B7-1 expression and function during the course of murine relapsing experimental autoimmune encephalomyelitis.

B7/CD28-mediated costimulation is a promising target for therapeutic intervention in autoimmune diseases. However, studies addressing the differential functional roles of B7-1 and B7-2 in several autoimmune models have resulted in conflicting data, perhaps due to the temporal dynamics of B7-1 and B7-2 surface expression on different cell types and/or at different sites during an autoimmune response. We examined the temporal expression of B7 costimulatory molecules in the CNS and in various lymphoid organs during the course of murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE). Following immunization of SJL mice with the immunodominant proteolipid protein epitope, PLP139-151, surface expression of B7-1 was up-regulated on B cells, T cells, and macrophages, relative to B7-2, on CNS-infiltrating cells and on splenocytes. Similar enhancement in splenic B7-1 expression could be induced in SJL mice by the adoptive transfer of PLP139-151-specific cells or by immunization with CFA alone. These changes were not observed on lymph node cells, including those isolated from lymph nodes draining the immunization site, which maintained the predominant B7-2 expression pattern seen in naive mice. These phenotypic expression patterns correlated with the functional predominance of B7-1 in costimulating T cell activation when employing APCs from the spleen or CNS of mice with ongoing R-EAE, while B7-2 remained functionally predominant on lymph node APCs. Variation of phenotypic expression and functional dominance of costimulatory molecule expression in different lymphoid compartments during an active inflammatory autoimmune response has important implications in immune regulation, autoimmune pathogenesis, and therapeutic strategies.

Animals↗

PubMed1998

Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a cross-reactive environmental antigen.

Cross-reactivity with environmental antigens has been postulated as a mechanism responsible for the induction of autoimmune disease. Experimental autoimmune encephalomyelitis is a T cell-mediated autoimmune disease model inducible in susceptible strains of laboratory animals by immunization with protein constituents of myelin. We used myelin proteolipid protein (PLP) peptide 139-151 and its analogues to define motifs to search a protein database for structural homologues of PLP139-151 and identified five peptides derived from microbial Ags that elicit immune responses that cross-react with this self peptide. Exposure of naive SJL mice to the cross-reactive environmental peptides alone was insufficient to induce autoimmune disease even when animals were treated with Ag-nonspecific stimuli (superantigen or LPS). However, immunization of SJL mice with suboptimal doses of PLP139-151 after priming with cross-reactive environmental peptides consistently induced experimental autoimmune encephalomyelitis. Furthermore, T cell lines from mice immunized with cross-reactive environmental peptides and restimulated in vitro with PLP139-151 could induce disease upon transfer into naive recipients. These data suggest that expansion by self Ag is required to break the threshold to autoimmune disease in animals primed with cross-reactive peptides.

Adoptive Transfer↗

PubMed1998

Stem cell transplantation for severe autoimmune diseases: progress and problems.

Since Morton and Siegel's epochal experiments 30 years ago animal models have been successfully utilized both for transfer and resolution of autoimmune diseases (AID). More recently human lymphocyte xenografts have reproduced clinical AID in SCID mice. Allogeneic stem cell transplantation demonstrated therapeutic potential in fully developed autoimmune disease. Mixed allogeneic chimerism induced by a sublethal approach has also been shown to prevent and even reverse autoimmune insulitis in nonobese diabetic (NOD) mice. More unexpectedly it was found that experimental adjuvant arthritis (AA) and experimental allergic encephalomyelitis (EAE) could be cured by means of total body irradiation (TBI) followed by autologous hemolymphopoietic stem cell (HSC) transplantation. It was postulated that the newly developing T cells might be tolerant to self antigens. The transfer of AID from affected donors to recipients of allogeneic HSC transplants has been reported for many organ-specific AID, including diabetes (IDDM), thyroiditis, myasthenia gravis and thrombocytopenic purpura (AITP); rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were not transferred. Conversely patients with the combination of AID and a severe blood disease (leukemia, aplasia) were cured of both diseases following allogeneic BMT, with the notable exception of a relapse in a patient with RA despite full donor engraftment. Allogeneic transplants are certainly more promising as far as concerns a resolution of AID, because they may also exert a graft-versus-autoimmunity effect by gradually eradicating the recipient's lymphopoiesis, but transplant related mortality (TRM) is considered still too high to employ this procedure consistently. New non-myeloablative conditioning regimens, designed to allow the donor's immune system to take over, are already utilized for malignant and non-malignant hematologic diseases, and may become an attractive option for severe, refractory AID. For the time being, however, autologous procedures are still safer, and are being utilized in many projects worldwide. The EBMT/EULAR Registry has collected over 70 patient reports. The more numerous and favorable results have been obtained up to now in multiple scleosis and in systemic lupus erythematosus; the worst in refractory autoimmune thrombocytopenic purpura. No definite conclusions as to the efficacy of autologous HSC transplantation, from marrow or from blood, with or without T-cell depletion, may be drawn at this time, but the feeling is that real cures will be very difficult to obtain by this approach, and that corticosteroid-free remissions and a general lowering of the autoimmune potential will be more realistic goals. Accurate comparisons with already existing aggressive immunosuppressive protocols will become necessary, if possible by means of prospective randomized clinical studies.

Adoptive Transfer↗

PubMed1997

[Interferon therapy and autoimmunity].

The treatment of viral hepatitis or malignomas with interferon (IFN) can increase the incidence of autoimmune disease. This paper reviews published case and study reports. The incidence of overt autoimmune diseases under IFN treatment is about 3%. Autoantibodies can be detected in 23% of the patients. Autoimmune thyroid diseases are the most frequent ones, but nearly all autoimmune diseases can occur. Beside benign and reversible courses chronic developments and lethal outcomes are possible. Actual concepts concerning the pathogenesis of IFN-associated autoimmunity include induction of MHC and other molecules as well as the modulation of lymphocyte functions. Clinical and paraclinical controls are necessary under treatment with IFN and during follow-up.

Anemia, Hemolytic, Autoimmune↗

PubMed2002

Immunoregulation of CNS autoimmunity by helminth and mycobacterial infections.

The 'hygiene hypothesis' has been proposed to explain apparent increases in autoimmune disease and allergy in areas of the world with improved health care and sanitation. This hypothesis proposes that the lack of serious childhood infections impairs development of an appropriately educated immune response. Imbalance of Th1 and Th2 responses and lack of regulatory T-cell populations are two of many proposed potential mechanisms for immune failures such as autoimmunity and allergy. We summarize the literature evidence for the influence of infectious organisms on autoimmunity with focus on helminth and mycobacterial infections. We also demonstrate that Schistosoma mansoni ova pretreatment, Mycobacterium bovis (BCG) infection, and lyophilized Mycobacterium tuberculosis all modify the course of clinical disease in mice induced for experimental autoimmune encephalomyelitis (a mouse model for human multiple sclerosis (MS)). Our data supports the applicability of the hygiene hypothesis to CNS autoimmune disease.

Animals↗

PubMed2000

Mapping and identification of autoimmunity genes.

Over the past several years, intense effort has been made to map the chromosomal locations of genes involved in the susceptibility to autoimmune diseases. The first phase of this mapping effort-performed in most cases by using microsatellite markers to scan the genome for loci that are linked with disease-has generated first-draft maps for numerous autoimmune diseases in humans, mice and rats, pointing to as many as 20 different loci in some diseases. The second phase is now beginning, with efforts focused on narrowing the loci sufficiently to allow the positional cloning of disease-associated alleles. From these mapping data it is clear that some of these loci overlap between various autoimmune diseases and preliminary results suggest that indeed there is a sharing of 'autoimmunity genes' between various autoimmune diseases.

Animals↗

PubMed2004

Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II.

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.

Addison Disease↗

PubMed2000

Target proteins in human autoimmunity: cytochromes P450 and UDP- glucuronosyltransferases.

Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are targets of autoantibodies in several hepatic and extrahepatic autoimmune diseases. Autoantibodies directed against hepatic CYPs and UGTs were first detected by indirect immunofluorescence as antiliver and/or kidney microsomal antibodies. In autoimmune hepatitis (AIH) type 2, liver and/or kidney microsomal (LKM) type 1 autoantibodies are detected and are directed against CYP2D6. About 10% of AIH-2 sera further contain LKM-3 autoantibodies directed against family 1 UGTs. Chronic infections by hepatitis C virus and hepatitis delta virus may induce several autoimmune phenomena, and multiple autoantibodies are detected. Anti-CYP2D6 autoantibodies are detected in up to 4% of patients with chronic hepatitis C, and anti-CYP2A6 autoantibodies are detected in about 2% of these patients. In contrast, 14% of patients with chronic hepatitis delta virus infections generate anti-UGT autoantibodies. In a small minority of patients, certain drugs are known to induce immune-mediated, idiosyncratic drug reactions, also known as 'druginduced hepatitis'. Drug-induced hepatitis is often associated with autoantibodies directed against hepatic CYPs or other hepatic proteins. Typical examples are tienilic acid-induced hepatitis with anti-CYP2C9, dihydralazine hepatitis with anti-CYP1A2, halothane hepatitis with anti-CYP2E1 and anticonvulsant hepatitis with anti-CYP3A. Recent data suggest that alcoholic liver disease may be induced by mechanisms similar to those that are active in drug-induced hepatitis. Autoantibodies directed against several CYPs are further detected in sera from patients with the autoimmune polyglandular syndrome type 1. Patients with autoimmune polyglandular syndrome type 1 with hepatitis often develop anti-CYP1A2; patients with adrenal failure develop anti-CYP21, anti- CYP11A1 or CYP17; and patients with gonadal failure develop anti-CYP11A1 or CYP17. In idiopathic Addison disease, CYP21 is the major autoantigen.

Autoantibodies↗

PubMed1995

The Yaa gene-mediated acceleration of murine lupus: Yaa- T cells from non-autoimmune mice collaborate with Yaa+ B cells to produce lupus autoantibodies in vivo.

The BXSB Y chromosome-linked mutant gene, Yaa, promotes autoimmune responses in mice predisposed to a lupus-like autoimmune disease. We have previously shown that a cognate interaction of T cells with B cells expressing the Yaa gene appears to be responsible for the accelerated production of autoantibodies. To investigate whether T cells that provide help for autoantibody production by Yaa+ B cells need to express the Yaa gene, we have made radiation bone marrow chimeras containing two sets of T and B cells from mice with or without the Yaa gene and differing by the Thy-1 and Igh allotypes. We then determined autoantibody production following the selective elimination of T cells of Yaa+ origin by treating mice with allele-specific anti-Thy-1 monoclonal antibody. Our results demonstrated that the selective production of autoantibodies by Yaa+ B cells in Yaa(+)-Yaa- double bone marrow chimeras can be mediated as efficiently by T cells from non-autoimmune mice lacking the Yaa gene as by T cells from autoimmune mice bearing the Yaa gene. This indicates that T cells from non-autoimmune Yaa- mice are capable of providing help for autoimmune responses by collaborating with Yaa+ B cells. These data thus strongly suggest that the Yaa gene defect is not functionally expressed in T cells, but only in B cells, and contrast with parallel experiments in the lpr model, in which defects of the Fas antigen in both T and B cells are crucial for the lpr gene-mediated promotion of autoantibody production.

Animals↗

PubMed2000

Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility.

Autoimmune diseases involve multiple genes. While functions of these genes are largely unknown, some may be related to an intrinsic hyperresponsiveness of B cells. B-cell responses are controlled by signaling thresholds through the B-cell antigen receptor (BCR) complex. The B1 isoform of type II IgG Fc receptors (FcgammaRIIB1) is exclusively expressed on B cells and serves as a negative regulator for inhibiting BCR-elicited activation. Thus, its allelic variants associated with functional deficits could be examined for possible associations with susceptibility to autoimmune diseases. We found that there are three types of polymorphisms in the reported FcgammaRIIB transcription regulatory regions in mouse strains. Compared to normal healthy mouse strains (group III), autoimmune disease-prone strains (group I) share three deletion sites: two in the promoter region and one in the third intron. Strains (group II) that per se are not autoimmune-prone, but have potentials to accelerate autoimmune diseases share two deletion sites in the third intron: one identical to that in group I and the other unique to group II. These polymorphisms correlated well with extents of down-regulation of FcgammaRIIB1 expression in germinal-center B cells upon stimulation with antigens and up-regulation of IgG antibody responses. Our data imply that these FcgammaRIIB polymorphisms are selected evolutionarily for natural defense against pathogens, and that such polymorphisms may, in turn, form the basis of one aspect of autoimmune susceptibility.

Animals↗

PubMed1996

Evidence for autoimmunity to myosin and other heart-specific autoantigens in patients with dilated cardiomyopathy and their relatives.

Autoimmune disease is characterised by the presence of circulating autoantibodies in the affected patients and in a proportion of their relatives. These antibodies are generally not pathogenic but are reliable markers of immune-mediated tissue damage. In organ-specific autoimmune disease, the destruction process is largely restricted to one organ within the body and the autoantibodies react with autoantigens which are unique to the diseased target organ. At least in a patient subset, myocarditis and dilated cardiomyopathy (DCM) may represent the acute and chronic stages of a progressive organ-specific autoimmune disease of the myocardium. Autoimmune features in patients with myocarditis/DCM include: familial aggregation, a weak association with HLA-DR4, abnormal expression of HLA class II on cardiac endothelium on endomyocardial biopsy, and detection of organ- and disease-specific cardiac autoantibodies, by immunofluorescence and absorption techniques, in the affected patients and in a proportion of their symptom-free relatives from both familial and non-familial DCM pedigrees. The organ-specific cardiac autoantibodies detected by immunofluorescence are directed against multiple antigens. One of these, first identified using immunoblotting and confirmed by ELISA, is the cardiac-specific alpha-myosin isoform. Myosin fulfils the expected criteria for organ-specific autoimmunity, in that immunisation with cardiac but not skeletal myosin reproduces, in susceptible mouse strains, the human disease phenotype of DCM; in addition, alpha-myosin is entirely cardiac-specific and is only expressed in the myocardium. Using ELISA, high titer organ- and disease-specific anti alpha-myosin antibodies have been found in 16% of the symptom-free relatives of DCM patients and in 38% of the pedigrees of the same cohort of relatives studied by immunofluorescence. The ELISA results provide additional evidence for autoimmunity in a subset of DCM families, and emphasise the importance of alpha-myosin as a target antigen.

Autoantibodies↗

PubMed2004

Mycophenolate mofetil prevents autoimmune glomerulonephritis and alterations of intrarenal adrenomedullin in rats.

We studied the effects of mycophenolate mofetil, a specific inhibitor of inosine monophosphate dehydrogenase, on the mercuric chloride induced autoimmune glomerulonephritis in Brown Norway rats and also on the renal contents of adrenomedullin. In the rats with autoimmune glomerulonephritis, plasma and renal tissue adrenomedullin levels were increased significantly. Coadministration of mycophenolate mofetil resulted in prevention of autoimmune glomerulonephritis and also in maintaining of plasma and renal tissue adrenomedullin levels at control levels. Adrenomedullin mRNA expressions in the renal cortex were also higher in the rats with autoimmune glomerulonephritis. Significant positive correlations were found between renal cortical adrenomedullin levels and urinary Na+ and N-acetyl-beta-D-glucosaminidase excretion. A significant negative correlation between renal cortical adrenomedullin levels and creatinine clearance was also found. These results suggest that mycophenolate mofetil suppresses the renal damage in rats with autoimmune glomerulonephritis and renal adrenomedullin may participate in the pathophysiology of autoimmune glomerulonephritis.

Adrenomedullin↗

PubMed2006

4. Autoimmunity, vasculitis, and autoantibodies.

Autoimmune diseases are distinct clinical syndromes characterized by various alterations in normal immune responsiveness, such that there is a loss of tolerance to particular host constituents. In most cases, despite years of intense investigation, the etiopathogenic antigens initiating these systemic inflammatory conditions remain undefined. However, a great deal has been learned about the changes in components of the immune response relevant to the propagation and sustenance of these often chronic disorders. In addition, various hormonal, environmental, physiologic, and other influences that affect their expression have been identified. The expression and ultimate clinical outcome of autoimmune diseases usually relate to inflammation-related damage to the target organ with subsequent dysfunction. Certain immune conditions, such as autoimmune thyroid disease, largely affect a single organ, whereas others, such as systemic lupus erythematosus, heterogeneously affect sundry organ systems. Autoantibodies directed against normal host antigens are a common feature of many autoimmune diseases. In some cases they are pathogenic, whereas in others they serve as markers for organ involvement or outcomes. Clinical descriptions of autoimmune diseases date back many decades in some cases. Recent efforts at formulating classification criteria have allowed clearer distinctions and more accurate stratification. Greater understanding of the immunopathogenesis of autoimmune conditions has led to the development and introduction into the clinic of novel immunomodulatory therapies and treatment paradigms that have substantially improved the outcomes for patients affected by these serious conditions.

Animals↗

PubMedDate not supplied

Detection of mRNA encoding H(1) receptor and iNOS by RT-PCR in autoimmune myocarditis with special reference to changes in heart contractility.

Cardiac tissue from autoimmune myocarditis mice was studied to evaluate the expression and biological activity of mRNA encoding H(1) receptor and iNOS. BALB/c inbred mice were immunized with heart protein and sacrificed at 20, 45 and 50 days post immunization. Heart contractility studies and RT-PCR assays were performed. Heart from autoimmune myocarditis mice show mRNA iNOS-related dysfunction with a decrease in heart contractility. This effect was accompanied with an increase production of cyclic GMP and was improved by treating autoimmune mice with an inhibitor of iNOS activity. In addition, autoimmune myocardium expressed an active histamine H(1) receptor mRNA coupled to phospholipase C. The activation of H(1) receptor by ThEA stimulated both phosphoinositide hydrolysis and heart contractility. Normal myocardium did not expressed neither iNOS mRNA nor H(1) receptor mRNA. In conclusions: the development of autoimmune cardiac dysfunction was associated with the expression of iNOS mRNA, cyclic GMP accumulation and the expression of an active histamine H(1) receptor mRNA with increase production of inositol phosphates. These protein emergence during the course of autoimmune myocarditis may be involved a distinct compensatory mechanism operating in this disease.

Animals↗

PubMed2002

Islet abnormalities in the pathogenesis of autoimmune diabetes.

Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that results in the destruction of the insulin-producing beta cells in the pancreatic islets of Langerhans. In spite of extensive genetic and immunological studies, mainly performed in the non-obese diabetic (NOD) spontaneous mouse model, the etiology of the autoimmune attack remains unknown. Several autoantigens have been identified and numerous studies have suggested a role for defective regulation of immune function. However, this account does not explain why the autoimmune process specifically affects the insulin-producing beta cells. Thus, abnormal immune regulation might explain the predisposition to autoimmunity in general, but additional factors should then determine the target of the autoimmune attack. Here, we review the evidence that abnormalities in islet cell differentiation and function exist that might trigger the immune system towards beta-cell autoimmunity in humans and NOD mice.

Animals↗

PubMed2001

CD40/154 blockade and rejection of islet allografts in the streptozotocin and autoimmune diabetic rat.

Islet transplantation in children with autoimmune diabetes will require immunosuppression that has minimal toxicity and side-effects, and overcomes the barrier of autoimmunity. Since antibodies directed against the CD40/154 co-stimulatory pathway may meet these criteria, we have tested the ability of hamster antirat CD154 (AH.F5, Biogen) to prevent rejection of renal subcapsular islet allografts in streptozotocin (STZ) or autoimmune (AUTO) diabetic diabetes-resistant biobreeding (DRBB) rats. STZ diabetic rats that received anti-CD154 at 15 mg/kg per dose but not 10 mg/kg per dose did not have evidence of rejection until about 80-120 d post-transplantation, by which time antibody concentrations had returned to undetectable levels. Rats retreated with anti-CD154 before recurrence of diabetes had a prolonged period of disease-free survival. Most of these rats had recurrence following a spleen cell challenge. In contrast, AUTO diabetic DRBB rats treated with anti-CD154 had recurrence of diabetes between 7 and 12 d following transplantation of the Dark Agouti (DA) islets. In a separate set, AUTO diabetic rats that received a simultaneous islet isograft, islet allograft and thyroid allograft had focal accumulation of lymphocytes at the periphery of the isograft, while the islet and thyroid allografts had diffuse infiltration with lymphocytes and destruction of tissue with no residual staining for glucagon. Therefore, autoimmunity adds an additional barrier to islet allotransplantation that is not overcome with CD40/154 blockade in an animal model that closely parallels autoimmune diabetes in humans. The results indicate the importance of testing regimen of islet transplantation in animal models of autoimmune diabetes.

Journal Article↗

PubMed2002

Helicobacter pylori, parietal cell antibodies and autoimmune gastropathy in type 1 diabetes mellitus.

BACKGROUND: Fifteen to 20% of type 1 diabetic patients exhibit parietal cell antibodies (PCA), which are associated with autoimmune gastritis, hypochlorhydria, iron deficiency and pernicious anaemia. AIM: To examine whether Helicobacter pylori infection could explain the high prevalence of PCA and autoimmune gastropathy in diabetes. If so, H. pylori eradication could prevent autoimmune gastritis. METHODS: In 229 type 1 diabetics (M/F: 135/94; age: 41 +/- 12 years) PCA were measured. H. pylori infection was assessed by serology, urea breath test in all and by histology (updated Sydney system) in 88 subjects. Pentagastrin tests were performed in 42 patients. RESULTS: Sixty-nine patients were PCA-positive. H. pylori infection was present in 72 patients and was negatively associated with HLA-DQA1*0103-B1*0603 (OR=0.12, P=0.015) and positively with DQA1*0501-B1*0201 (OR=1.9, P=0.032). PCA-positivity was linked to HLA-DQA1*0501-B1*0301 (OR=3.9, P=0.017). A link between H. pylori and PCA was observed when PCA-positivity was defined as a titre > or = 1/20 (OR=2.0, P=0.03), but not if > or =1/40 was the cut-off point. PCA-positivity, but not H. pylori infection, was associated with iron deficiency anaemia (OR=2.7, P=0.008), pernicious anaemia (OR= 33.5, P < 0.0001), hypochlorhydria (OR=12.1, P=0.0008) and autoimmune gastritis (OR=12.5, P < 0.0001). CONCLUSIONS: The HLA-bound susceptibility of H. pylori and PCA differed. PCA-positivity but not ongoing H. pylori infection is associated with autoimmune gastritis. Low titres of PCA might reflect H. pylori infection rather than autoimmune gastropathy.

Adult↗