Helicobacter pylori and skin autoimmune diseases

Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori(H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins(HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Beh et’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review.     

Helicobacter pylori and autoimmune disease:Cause or bystander

Helicobacter pylori(H.pylori)is the main cause of chronic gastritis and a major risk factor for gastric cancer.This pathogen has also been considered a potential trigger of gastric autoimmunity,and in particular of autoimmune gastritis.However,a considerable number of reports have attempted to link H.pylori infection with the development of extra-gastrointestinal autoimmune disorders,affecting organs not immediately relevant to the stomach.This review discusses the current evidence in support or against the role of H.pylori as a potential trigger of autoimmune rheumatic and skin diseases,as well as organ specific autoimmune diseases.We discuss epidemiological,serological,immunological and experimental evidence associating this pathogen with autoimmune diseases.Although over one hundred autoimmune diseases have been investigated in relation to H.pylori,we discuss a select number of papers with a larger literature base,and include Sj grens syndrome,rheumatoid arthritis,systemic lupus erythematosus,vasculitides,autoimmune skin conditions,idiopathic thrombocytopenic purpura,autoimmune thyroid disease,multiple sclerosis,neuromyelitis optica and autoimmune liver diseases.Specific mention is given to those studies reporting an association of anti-H.pylori antibodies with the presence of autoimmune disease-specific clinical parameters,as well as those failing to find such associations.We also provide helpful hints for future research.     

Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

AIM: To compare the prevalence of Helicobacter pylori(Hpylori) infection in autoimmune thrombocytopenic purpura (AITP) patients with that of nonthrombocytopenic controls,and to evaluate the efficacy of the treatment in Hpylori(+)and Hpylori(-) AITP patients.METHODS: The prevalence of gastric Hpyloriinfection in 38 adult AITP patients (29 female and 9 male; median age 27 years; range 18-39 years) who consecutively admitted to our clinic was investagated.RESULTS: Hpyloriinfection was found in 26 of 38 AITP patients (68.5%). Hpyloriinfection was found in 15 of 23 control subjects (65.2%). The difference in Hpyloriinfection between the 2 groups was not significant. Thrombocyte count of Hpylori-positive AITP patients was significantly lower than that of Hpylori-negative AITP patients (P＜0.05).Thrombocyte recovery of Hpylori-positive group was less than that of Hpylori-negative group (P＜0.05).CONCLUSION: Hpyloriinfection should be considerecd in the treatment of AITP patients with Hpyloriinfection.     

Ins and outs of Helicobacter pylori association with autoimmune rheumatic diseases

Helicobacter pylori (H. pylori) infection is widely prevalent throughout worldwide. H. pylori manage a long-term survival in hostile environment of human stomach leading to peptic ulcer diseases and gastric cancer. But mostly infected person remains asymptomatic. Its chronic interaction with immune system makes H. pylori as an attractive candidate for the researchers to study its association with autoimmune diseases. This article presents a review of the literature on the association of H. pylori infection in selective autoimmune rheumatic diseases (RD). The authors used MeSH terms “Helicobacter pylori” with “rheumatoid arthritis,”“systemic lupus erythematosus,” or “fibromyalgia” to search PubMed database. All relevant studies identified were included. Despite extensive medical advancement many questions on role of H. pylori infection in autoimmune RD still remain unanswered. Further studies are therefore needed to address the role of H. pylori in pathogenesis of RD.     

Role of Helicobacter pylori infection in autoimmune systemic rheumatic diseases

The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori (H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords “rheumatoid arthritis”, “Sjögren’s syndrome”, “systemic sclerosis”, “systemic lupus erythematosus”, “Helicobacter pylori” and “pathogenesis”. A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article I review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted.     

Inhibitory effects of Helicobacter pylori infection on murine autoimmune gastritis

BACKGROUND AND AIM: Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the effects of H pylori infection on the pathophysiology of AIG in mice. MATERIALS AND METHODS: BALB/c nu/nu mice (n=40) with or without H pylori infection received splenocytes from neonatally thymectomised mice to induce AIG. Half of the mice were orally infected with H pylori prior to AIG induction. Histological findings, and local and systemic immune responses were serially evaluated. RESULTS: Two and six months after transfer, parietal cells in uninfected mice were depleted while those in infected mice were well preserved. The degree of gland atrophy (p<0.01), hyperplasia (p<0.01), gastric pH (p<0.05), and serum gastrin levels of infected mice were significantly lower than those of uninfected mice. Serum antiparietal cell antibody levels gradually decreased in infected mice, and were significantly lower than those of uninfected mice at six months (p<0.05). Real time polymerase chain reaction studies revealed significantly higher interleukin 4 (p<0.05) and transforming growth factor beta (p<0.05) gene expression in the gastric mucosa in infected mice than in uninfected mice at both two and six months after AIG induction. CONCLUSIONS: H pylori infection inhibited the development of AIG in mice. Th2-type immune responses and transforming growth factor beta in the gastric microenvironment might be involved in the inhibitory effects of H pylori infection on the development of AIG, in which Th1-type responses have an important role.     

Helicobacter pylori infection and autoimmune processes: an emerging field of study

Evidence is accumulating that Helicobacter pylori infection may be closely associated with autoimmunity. However, whether autoimmunity plays a causal role in the pathogenesis of some of the diseases attributed to this bacterium or whether it is rather an epiphenomenon remains to be determined. In this brief review, a summary is made of current knowledge regarding the potential general mechanisms by which Helicobacter pylori causes mucosal damage. A review is then made of the evidence linking this bacterium to the production of different gastric autoantibodies. Finally, the reported association between Helicobacter pylori infection and some known autoimmune diseases is discussed. Although the data are still not sufficiently complete to draw definite conclusions, autoimmunity appears to be an important aspect of this infection and will certainly become a major field of study in the next few years.     

Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection

AIM:To study the association between Helicobacter pylori(H.pylori)infection and autoimmune type atrophic gastritis. METHODS:Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology,immunoblot-based serology,and histology to reveal a past or a present H.pylori infection.In addition,serum markers for gastric atrophy(pepsinogenⅠ,pepsinogenⅠ/Ⅱand gastrin)and autoimmunity[parietal cell antibodies(PCA), and intrinsic factor(IF),antibodies]were determi...     

Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection

AIM:To study the association between Helicobacter pylori(H.pylori)infection and autoimmune type atrophic gastritis. METHODS:Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology,immunoblot-based serology,and histology to reveal a past or a present H.pylori infection.In addition,serum markers for gastric atrophy(pepsinogenⅠ,pepsinogenⅠ/Ⅱand gastrin)and autoimmunity[parietal cell antibodies(PCA), and intrinsic factor(IF),antibodies]were determi...     

Levamisole-associated neutropenia and autoimmune granulocytotoxins.

To investigate possible immune mechanisms responsible for levamisole-associated neutropenia we tested patients with bladder cancer on levamisole therapy. Autoimmune and complement-dependent granulocytotoxic antibodies were detected in 3 patients with levamisole-induced neutropenia. The granulocytopenia appeared to be causally related to the presence of autoantibodies in that pretreatment serum or serum obtained after the restoration of neutrophil counts showed diminished or no granulocytotoxic reactivity. In addition, granulocytotoxins were found in 6 out of 20 (30%) patients receiving levamisole compared to only 2 out of 28 (7.1%) patients on no levamisole or placebo (P less than 0.06). Hence, screening for granulocytotoxins may forewarn of neutropenia in patients receiving levamisole for a variety of clinical diseases.     

Anti-granulocyte opsonic activity and autoimmune neutropenia

Sera from patients with unexplained neutropenia have been assayed for anti-granulocyte opsonic activity using a chemiluminescence technique which measures the metabolic response of human monocytes to antibody-coated granulocytes. This rapid and simple technique was more sensitive than indirect immunofluorescence in the detection of anti-granulocyte antibodies. Anti-granulocyte opsonic activity was detected in sera from 17 of 31 patients, suggesting that their neutropenia may have had an autoimmune basis. The opsonic activity of five of the 17 sera was increased when granulocytes were sensitized in the presence of fresh serum. Four of these sera bound IgM and C3b to granulocytes in the immunofluorescence test. Human IgG when added to the monocyte suspension medium inhibited monocyte response to IgG antibody-opsonized granulocytes. This inhibition was less when granulocytes were opsonized with sera containing IgM and complement granulocyte-binding activity. This observation may be relevant to the selection of neutropenic patients for therapeutic use of intravenous immunoglobulin.     

Severe autoimmune neutropenia associated with acute autoimmune hepatitis

A 49-year-old previously healthy female presented with acute hepatitis and severe neutropenia. A diagnosis of type 1 autoimmune hepatitis was made based on the histological appearance of a liver core biopsy, positive anti-smooth muscle antibodies, and positive anti-neutrophil cytoplasmic antibody (atypical ANCA). Hemogram revealed mild leukopenia with severe neutropenia (absolute neutrophil count 256/mm³), normal hemoglobin and mild thrombocytopenia (115000/mm³). A bone marrow biopsy and aspirate had a normal karyotype, increase in granulopoiesis, prominence of promyelocytes (31%) and absence of mature granulocytes. Anti-neutrophil antibodies were detected in the patient’s blood. Therapy was directed at the underlying hepatitis with resolution of neutropenia without the use of colony-stimulating factors.     

Helicobacter pylori

The diagnostics and treatment of Helicobacter pylori infections have substantially changed in recent years. Instead of a general test-and-treat strategy, differentiated treatment methods are increasingly being used. Practical problems in many cases were that a useful combination was often not employed after the failure of an initial antibiotic treatment. In 2009 new guidelines on the diagnostics and treatment of Helicobacter pylori infections were published. Various expert groups from gastro-enterology, microbiology and rheumatology provided new general frameworks and concrete treatment suggestions for Helicobacter pylori infections of the stomach. The statements are grouped according to ?should“ and ?can“ recommendations and the consensus opinion is divided into various subgroups. The new S3 guidelines specify the therapy indications with respect to first and second line procedures and now give different durations of therapy (7 days for first line, 10 days for second line after treatment failure) as well as concrete algorithms. Before treatment two positive diagnostic procedures are required because the prevalence in Germany is decreasing. In addition to the rapid test and histological investigations, the 13-C breath test and stool tests with excellent sensitivity and specificity are also now available. Probiotics can improve therapy success especially for long-term antibiotic regimes and in the future bismuth could again play an increasingly more important role because antibiotic resistance to metronidazol and clarithromycin is increasing.     

Helicobacter pylori

Helicobacter pylori is associated with various gastroduodenal diseases such as peptic ulcer, functional dyspepsia, MALT lymphoma and distal gastric cancer. Diagnosis of H. pylori can be established by non-invasive (^13Curea breath test, stool antigen test, serology) and invasive (histology, rapid urease test, culture) tests. In adults, culture and susceptibility testing should or must be performed after failing of first-line therapy in case of a control endoscopy and before third-line therapy, respectively. Peptic ulcer and gastric MALT lymphoma represent obligatory indications for eradication therapy. Other potential indications are functional dyspepsia, prevention of gastric cancer in individuals being at risk, and before starting treatment with traditional non-steroid antiphlogistics. First-line therapy is performed with a 7-days combination of proton pump inhibitor with clarithromycin and amoxicillin or metronidazole. In second-line therapy levofloxacin and rifabutin are good rescue antibiotics.     

Helicobacter pylori

PURPOSE OF REVIEW: Helicobacter pylori is an important human pathogen, responsible for most peptic ulcer disease, gastritis and gastric malignancies. H. pylori has several unique features: it is highly adapted for gastric colonization, yet it produces clinical consequences in a small minority, its genome is known, and it is the only bacterium strongly associated with cancer. H. pylori is therefore of great interest to clinicians and researchers of many, often disparate, disciplines. We highlight recent advances in this fast changing field from many different areas. RECENT FINDINGS: The major contentious clinical issues relate to the synergistic gastrotoxic interactions of H. pylori with non-steroidal anti-inflammatory drugs, and a possible association of H. pylori with atherosclerotic events. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. Studies of pathogenesis have been aided by increasingly sophisticated murine models. The effects in gastric epithelial cells of two of the major virulence factors (genes within the cag pathogenicity island and the vacuolating cytotoxin, VacA) of H. pylori illustrate the complex network of cellular reactions activated by H. pylori. The metabolism of H. pylori is dependent on the availability of hydrogen. SUMMARY: Basic science research into H. pylori continues to elucidate the mechanisms by which H. pylori infection causes disease. These findings have implications for the design of novel therapies and for improving clinical strategies to identify at-risk individuals. Many are also worthy of consideration for other epithelial-microbial interactions.