Vaccine development against Helicobacter pylori: from ideal antigens to the current landscape.

Introduction: The interest of the world scientific community for an effective vaccine against Helicobacter pylori infection arises from its high prevalence and association with many diseases. Moreover, with an immunological response that is not always effective for the eradication of the bacteria and an increasing antibiotic resistance in the treatment of this infection, the search for a vaccine and new therapeutic modalities to control this infection is urgent.Areas covered: We bring an overview of the infection worldwide, discussing its prevalence, increasing resistance to antibiotics used in its therapy, in addition to the response of the immune system to the infection registered so far. Moreover, we address the most used antigens and their respective immunological responses expected or registered up to now. Finally, we address the trials and their partial results in development for such vaccines.Expert opinion: Although several studies for the development of an effective vaccine against this pathogen are taking place, many are still in the preclinical phase or even without updated information. In this sense, taking into account the high prevalence and association with important comorbidities, the interest of the pharmaceutical industry in developing an effective vaccine against this pathogen is questioned.

Helicobacter pylori infection: Beyond gastric manifestations.

Helicobacter pylori (H. pylori) is a bacterium that infects more than a half of world's population. Although it is mainly related to the development of gastroduodenal diseases, several studies have shown that such infection may also influence the development and severity of various extragastric diseases. According to the current evidence, whereas this bacterium is a risk factor for some of these manifestations, it might play a protective role in other pathological conditions. In that context, when considered the gastrointestinal tract, H. pylori positivity have been related to Inflammatory Bowel Disease, Gastroesophageal Reflux Disease, Non-Alcoholic Fatty Liver Disease, Hepatic Carcinoma, Cholelithiasis, and Cholecystitis. Moreover, lower serum levels of iron and vitamin B12 have been found in patients with H. pylori infection, leading to the emergence of anemias in a portion of them. With regards to neurological manifestations, a growing number of studies have associated that bacterium with multiple sclerosis, Alzheimer's disease, Parkinson's disease, and Guillain-Barré syndrome. Interestingly, the risk of developing cardiovascular disorders, such as atherosclerosis, is also influenced by the infection. Besides that, the H. pylori-associated inflammation may also lead to increased insulin resistance, leading to a higher risk of diabetes mellitus among infected individuals. Finally, the occurrence of dermatological and ophthalmic disorders have also been related to that microorganism. In this sense, this minireview aims to gather the main studies associating H. pylori infection with extragastric conditions, and also to explore the main mechanisms that may explain the role of H. pylori in those diseases.

Chronic catastrophic-like antiphospholipid syndrome: a "smoldering" variant?

Catastrophic antiphospholipid syndrome (CAPS) is characterized by life-threatening diffuse thrombotic manifestations involving particularly small vessels of kidney, lungs, brain and skin. We report a 20-year-old female with systemic lupus erythematosus and secondary antiphospholipid syndrome who presented typical organ and histological involvement as seen in CAPS but with protracted course suggesting a "smoldering" form of the disease.

Profile of autoantibodies in Jaccoud's arthropathy.

OBJECTIVE: To compare the frequency of different autoantibodies in a group of patients with Jaccoud's arthropathy (JA) secondary to systemic lupus erythematosus (SLE) with those without JA. METHODS: A group of SLE patients with JA was compared with another group of SLE patients without this complication, matched by age and gender, regarding the presence of autoantibodies. Antibodies to cyclical citrullinated peptides (anti-CCP) and to mutated citrullinated vimentin (anti-MCV) as well as anti-SSA/Ro, anti-SSB/La, anti-Sm and anti-RNP and anticardiolipin (aCL) antibodies were searched by ELISA, using commercial kits. Rheumatoid factor was determined by nephelometry and antinuclear and anti-dsDNA antibodies by IIF. RESULTS: Forty-eight individuals were included in the study, being 24 patients with JA and 24 without JA, matched by gender and age. The frequency of anti-CCP antibodies in the whole population was 12.5% (6 cases), with no difference between the 2 groups. Anti-MCV antibodies were detected in 10.4% (5 cases), being found only in those with JA (p=0.05). There was no association between the presence of JA and aCL, anti-Sm, anti-RNP and anti-SSB/La antibodies. On the other hand, a statistically significant association between the presence of anti-dsDNA antibodies and JA was observed (p=0.04) as well as a marginal association with a decrease in serum levels of C3 (p=0.06). CONCLUSION: In the present study, there was an association between the presence of JA and anti-dsDNA antibodies, and anti-MCV antibodies were found only in those SLE patients with JA. Whether these antibodies have an etiopathogenic role in JA is entirely unknown.

NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheumatoid arthritis.

Biomarkers of clinical response to rituximab (RTX) therapy and early predictors of outcome are still under investigation. We report a flow cytometric immunophenotyping analysis from peripheral blood leukocyte subpopulations of two patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment with RTX. Our results show a reduced population of CD19(+) expressing cells (B cells) after RTX treatment in all three patients. Increased frequency of peripheral regulatory CD4(+)CD25(high) T cell subset and the CD3(-)CD16(-)CD56(bright) NK cell subset after RTX therapy were also observed in all patients, the latter being more pronounced in the SLE patient with sustained clinical response. In addition, an increased population of NKT cell subsets was observed in the patients with clinical response. This is the first evaluation of NK and NKT cells as biomarkers of clinical response after rituximab therapy in rheumatic diseases.