The role of Th17 lymphocytes in the autoimmune and chronic inflammatory diseases

The emerging role of interleukin-17 as a hallmark proinflammatory cytokine of the adaptive immune system produced by a new T helper cell subset termed “Th17” has received considerable attention. In this review we will focus on recent information regarding IL-17 and its relevance in autoimmune and chronic inflammatory diseases.     

Immunization of patients with autoimmune inflammatory rheumatic diseases (the EULAR recommendations)

The European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) have been recently published. These evidence-based recommendations were based on existing literature in combination with expert opinion. Although patients with AIIRD are at increased risk of suffering from (complicated) infectious diseases--and vaccination seems a tool to reduce this risk--still many questions and controversies remain for the individual patient. In this overview, taking influenza as an example, the background of the recommendations, their clinical implications, and the direction of future research are discussed. The increase in knowledge on vaccine-preventable infections will allow us to further improve vaccination strategies.     

趋化因子配体CCL21与慢性炎症性疾病的关系

近些年来,趋化因子和各种临床疾病的相关关系得到了越来越多的国内外学者的关注.趋化因子配体21(chemokine ligand 21,CCL21)作为趋化因子大家族中的一员,诱导淋巴细胞向次级淋巴组织归巢,参与了多种慢性炎症性疾病的发病过程.现就CCL21与慢性炎症性疾病的研究进展作一简要综述,希望为临床上慢性炎症性疾...     

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4).METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT).RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sjögren’s syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto’s thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level.CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.     

Antineutrophil cytoplasmic autoantibodies in autoimmune liver and inflammatory bowel diseases

Abstract: Perinuclear antineutrophil cytoplasmic autoantibodies have been described in inflammatory bowel diseases and in primary sclerosing cholangitis. Because the data concerning their occurrence are conflicting, we have used indirect immunofluorescence on ethanol-fixed neutrophils to test the sera from a large population of 382 patients with various liver and digestive diseases: in particular, from 27 patients with primary sclerosing cholangitis, 105 patients with autoimmune chronic active hepatitis, 30 patients with primary biliary cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative colitis and 15% in Crohn's disease. They would not be helpful in the differential diagnosis between these two inflammatory bowel diseases. Within the group of autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies were detected in 44% of sera from patients with primary sclerosing cholangitis and in 36% of sera from patients with type I autoimmune active hepatitis, but not in primary biliary cirrhosis. When primary sclerosing cholangitis was associated with an inflammatory bowel disease, the prevalence of these autoantibodies was 60%. They were 88% specific for primary sclerosing cholangitis and 86% specific for type I autoimmune active hepatitis. Despite their moderate sensitivity and specificity in primary sclerosing cholangitis, they remain the only serologic marker of this autoimmune liver disease. Moreover, they turned out to be a more sensitive marker for inflammatory bowel disease with associated primary sclerosing cholangitis     

Common anti-infective prophylaxis and vaccinations in autoimmune inflammatory rheumatic diseases

An exhilarating era for autoimmune inflammatory rheumatic diseases (AIRD) has arrived; new therapeutics are emerging that not only control symptoms, but also may allow a chance for remission. However, enthusiasm must be tempered with judicious caution as gaps in our knowledge remain regarding long-term safety data especially with respect to new onset infections and reactivation of latent infections such as tuberculosis (TB). Chronic vigilance and appropriate anti-infective measures such as trimethoprim/sulphamethaxozole and TB chemoprophylaxis should be instituted whenever indicated to minimise risk. Vaccination is an appropriate choice to prevent substantial number of these infections. In this context, pneumococcal and influenza vaccines are the best evaluated and are recommended by standard vaccination guidelines by most of experts. Some studies have found mildly impaired immune responses to vaccines among patients receiving long-term immunosuppressive therapy and tumour necrosis factor (TNF) antagonists, but post vaccination antibody titres are frequently adequate to provide shield for the majority of immunised individuals. The accumulated data on the safety and effectiveness of vaccines warrant immunisation with the majority of vaccines for patients with AIRD with the exception of live vaccines. In India, however there is a concern about futility of influenza vaccine, as it is feared that the serotypes targeted in this vaccine may not be the prevailing in our geographic area. Vaccination status assessment as soon as diagnosis of any of AIRDs is established and updating to appropriate vaccination status should compulsorily be implemented in daily clinical practice by rheumatologists.     

Eicosanoids in chronic inflammatory intestinal diseases

Eikosanoids (prostaglandins, thromboxanes, prostacyclins, hydroxyfatty acids, leucotriens) are metabolites of arachidonic acid and are of importance for many functions of the gastro-intestinal tract. They increase the enteral secretion of water, sodium and chloride ions, stimulate inflammatory and immune reactions, inhibit the proliferation of the colon epithelium and regulate by means of cytoprotection the peristalsis and the intestinal blood supply. Though in chronic inflammatory intestinal diseases the concentrations of metabolites of arachidonic acid are increased up to now there are no conclusive proofs for their causal pathogenetic role.     

Arterial stiffness in chronic inflammatory diseases

Chronic inflammatory diseases are associated with premature atherosclerosis; however, it is unknown whether arterial stiffness is increased in this setting, possibly as a manifestation of vascular disease preceding and/or independent of atherosclerosis. Carotid ultrasonography and radial applanation tonometry were performed in 101 patients with systemic lupus erythematosus, 80 patients with rheumatoid arthritis, and 105 healthy control subjects. The 3 groups were comparable in age, gender, and carotid artery absolute and relative wall thickness. Atherosclerotic plaque was more common in lupus (46%) and rheumatoid arthritis (38%) patients than in controls (23%) (P<0.003). Although control subjects had higher central and peripheral blood pressures, arterial stiffness was increased in patient groups compared with controls (lupus, rheumatoid arthritis, controls, respectively: beta: 3.36 versus 3.22 versus 2.60, P<0.001; Young's modulus: 441 versus 452 versus 366 mm Hg/cm, P=0.004; Peterson's elastic modulus: 278 versus 273 versus 216 mm Hg, P<0.001) after adjustment for differences in mean brachial pressure. In multivariate analysis involving the entire population, arterial stiffness was independently related to age, serum glucose, and the presence of chronic inflammatory disease. In multivariate analysis restricted to the patients, arterial stiffness was independently related to age at diagnosis, disease duration, serum cholesterol, and C-reactive protein (and IL-6, when substituted for C-reactive protein). When analyses were repeated in the 186 study subjects without carotid plaque, arterial stiffness remained significantly elevated in patient groups after adjustment for differences in age and mean brachial pressure. In conclusion, arterial stiffness is increased in chronic inflammatory disorders independent of the presence of atherosclerosis and is related to disease duration, cholesterol, and the inflammatory mediator C-reactive protein and the cytokine that stimulates its production, IL-6.     

Diarrhea in chronic inflammatory bowel diseases

Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea.     

Probiotics and prebiotics in chronic inflammatory bowel diseases

INTRODUCTION At birth, the gastrointestinal tract is a sterile environment. Initial exposure of the gut to microbes occurs during the birthing process from the maternal fecal and vaginal ? ora. Within a few months after birth, a relatively stable microbia…     

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

AIM To investigate whether immune mediated diseases(IMD) are more frequent in patients with inflammatory bowel disease(IBD).METHODS In this population based registry study,a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16,2013. Controls were randomly selected from the Danish Civil Registration System(CRS) and matched for sex,age,and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis(UC),Crohn's disease(CD) and Both the latter referring to those registered with both diagnoses. Subsequently,odds-ratios(OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P 0.00125. P-values were estimated using Fisher's exact test.RESULTS There were significantly more women than men in the registry,and a greater percentage of comorbidity in the IBD groups(P 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased(P 0.00125) for primary sclerosing cholangitis(PSC),celiac disease,type 1 diabetes(T1D),sarcoidosis,asthma,iridocyclitis,psoriasis,pyoderma gangrenosum,rheumatoid arthritis,and ankylosing spondylitis. Restricted to UC(P 0.00125) were autoimmune hepatitis,primary biliary cholangitis,Grave's disease,polymyalgia rheumatica,temporal arteritis,and atrophic gastritis. Restricted to CD(P 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC(P 0.00125) were atrophic gastritis,rheumatoid arthritis,temporal arteritis,and polymyalgia rheumatica. Restricted to women with CD were episcleritis,rheumatoid arthritis,and psoriatic arthritis. The only disease restricted to men(P 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.     

(Auto)antibodies in inflammatory bowel diseases

Patients who have inflammatory bowel diseases (IBD) express strong antibody responses to a variety of epitopes. A number of (auto)antibodies have been described in patients who have Crohn's disease or ulcerative colitis. These markers reflect a loss of tolerance toward bacterial and fungal flora and have been studied for their clinical value in IBD patients. However, currently, they have no place in the diagnostic work up. Their real promise may lie in their use as surrogate markers of complicated aggressive disease as shown in various retrospective studies, but prospective data are lacking.     

Pregnancy and chronic inflammatory bowel diseases]

Chronic diseases have influence on fertility and course of pregnancy. Altogether 107 women who suffered from ulcerous colitis and Crohn's disease, respectively, were examined. The average weight and the size of the new-born after manifestation did not differ from those before the beginning of the disease. Low birth weight were observed after the medication of prednisolone and a manifestation of the ulcerous colitis during the gravidity. The ability for conception is not restricted when this disease is existing. An infertility rate being above the norm of the total population is to be found in Crohn's disease. There is no correlation to the localisation of the changes. It can be consented to a pregnancy in lacking Crohn's disease or in a mild activity of this disease. When there are moderately severe and severe attacks before the realization of the wish of having a child a dietetic, medicamentous or surgical therapy is to be recommended. The treatment with low-dosed azulfidine and corticosteroid has no influence on the development of the child. A prophylactic therapy is indicated in ulcerative colitis, an interruption is rarely to be proved. In an acute attack during the pregnancy, when the accurate diagnosis is imperative the fully effective dose in therapy is to be aspired to.     

Ophthalmologic complications in chronic inflammatory intestinal diseases

Through investigations which we performed ophthalmological complications in chronic inflammatory intestinal disease are revealed. It could be demonstrated that in most cases ocular symptoms are associated with joint troubles which in their turn depend on the severity of the general disease. Especially in elderly patients with longstanding history it is important to co-operate with representatives of other medical branches in the control of ocular complaints, since there may quickly occur functional deterioration when the eye is also involved.     

B-cell lymphoproliferation in chronic inflammatory rheumatic diseases

Patients with chronic inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and especially primary Sj?gren's syndrome (SS), are at higher risk than the general population of developing B-cell non-Hodgkin lymphoma (NHL). Analyses of the association between various lymphoma subtypes and specific disease entities suggest that this association might be mediated by disease-specific mechanisms, as well as by mechanisms unique to lymphoma subtype. These specific associations can provide important information about abnormal B-cell stimulation in these conditions. Patients with primary SS, SLE and RA are at high risk of developing diffuse large B-cell lymphomas, a group of high-grade NHLs with remarkable heterogeneity. Patients with primary SS are at particularly high risk of developing marginal-zone B-cell lymphomas. The risk factors of lymphoma development in primary SS seem to be closely related to the underlying mechanisms of abnormal stimulation and/or impaired censoring mechanisms of B cells. In patients with RA and SLE, more intense disease activity and/or long-lasting disease might be indications of a higher risk of lymphoma development. This Review will focus on the risk of lymphoma, common and disease-specific mechanisms of B-cell lymphoma development, and on the clinical consequences of lymphoma in patients with inflammatory rheumatic diseases.     

Idiopathic (autoimmune) chronic urticaria.

A case of idiopathic chronic urticaria (CU) is described briefly. The clinical characteristics, pathogenesis, diagnosis, and management of this disease are discussed followed by clinical pearls and pitfalls for the practicing allergist as well as the immunologist. CU, defined as recurring attacks of hives lasting for >6 weeks, is a common disorder for which the cause is determined in <20% of patients. Although the pathogenesis of idiopathic CU is not certain, the immune dysregulation/disruption causing autoimmunity is blamed. The diagnosis is based principally on the patient's history. Autologous serum skin test possibly should be performed in older children as a screening test for idiopathic autoimmune CU. This test shows the availability of serum IgG autoantibodies directed against the alpha-chain of FcepsilonRI. However, basophil mediator release assay still is accepted as a gold standard. Treatment is aimed first at avoiding underlying causative factors. Medications varying from H1-antihistamines to plasmapheresis as well as immunosuppressive therapies should be considered depending on clinical improvement. Spontaneous resolution of the disease is probable also.