Three interconnected positions are advocated: (1) although serving as a useful model, the immune self does not exist as such; (2) instead of a self/nonself demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self' or attack the 'other;' but exhibits a spectrum of responses, which when viewed from outside the system appear as discrimination of 'self' and 'nonself' based on certain criteria of reactivity. When immune reactions are conceived in terms of normal physiology and open exchange with the environment, where borders dividing host and foreign are elusive and changing, host defense is only part of the immune system's functions, which actually comprise two basic tasks: protection, i.e., to preserve host integrity, and maintenance of organismic identity. And thus (3) if the spectrum of immunity is enlarged, differentiating low reactive 'autoimmune' reactions from activated immune responses against the '...

This is a literature review about large granular lymphocyte leukemia (LGLL), a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL) or NK-cells (NK-LGLL) in the bone marrow and/or peripheral blood. The clinical features of LGLL include cytopenias (anemia, neutropenia and thrombocytopenia), lymphocytosis (usually discrete), lymphadenopathy, hepatomegaly, splenomegaly, immune abnormalities and constitutional symptoms (fever, night sweats and weight loss). The diagnosis is based on the confirmation of the clonality of T-cells or NK-cells (polymerase chain reaction and Southern blot are the two methods most commonly used) and typical findings of the immunophenotypic analysis of peripheral blood lymphocytes (flow cytometry analyses for specific surface antigens). In contrast to the chronic and indolent course of T-LGLL, NK-LGLL has an acute presentation and poor clinical outcome. There are different current treatment options, depending on clinical presentation.

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.

Multi-organic failure in the context of autoimmune diseases is a multi-factorial condition where different pathways concur to produce a global system breakdown. Some of these pathways include the coagulation, fibrinolysis, kinin and complement cascades which in normal conditions work together to provide a comprehensive response to injury. In pathologic conditions these regulatory mechanisms are replaced by positive feed-back loops. The common response pattern is the activation of the immune system via endothelium activation. Furthermore, these different plasma-driven mechanisms may induce standardised endothelial cell responses of which the most relevant are the activation of p38, JNK, NF-kβ and IRF-3 pathways. In this paper we review the common points between these major pathways and how they become activated, contributing to a global clinical picture. We present two examples of apparently different clinical settings, caused by the same global dysfunction: the Macrophage Activation Syndrome and the iatrogenic "cytokine storm" triggered by the administration of anti-CD28 monoclonal antibody TGN1412 in a phase 1 trial.

Autoantibodies neutralizing human ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif), the metalloprotease that physiologically cleaves von Willebrand factor, are a major cause of severe deficiency of the protease and of acquired thrombotic ...

Dendritic cells (DC), considered as immunological sentinels of the organism since they are antigen presenting cells, create the link between innate and adaptive immunity. DC include myeloid dendritic cells (MDC) and plasmacytoid dendritic cells (PDC). The presence of PDC, cells capable of producing large quantities of interferon alpha (IFN-alpha) in response to pathogenic agents or danger signals, seems to be closely related to pathological conditions. PDC have been observed in inflammatory immunoallergic dermatological disorders, in malignant cutaneous tumours and in cutaneous lesions of infectious origin. They seem to play a crucial role in the initiation of the pathological processes of autoimmune diseases such as lupus or psoriasis. Their function within a tumour context is not as well known and is controversial. They could have a tolerogenic role towards tumour cells in the absence of an activator but they also have the capacity to become activated in response to Toll-like rece...

The authors describe a clinical case of cutaneous candidiasis in a dog with dermatological lesions, characterized by persistent alopecia, crusts, ulcers and scales. Predisposing factors such as the use of corticosteroids, the concomitan presence of an autoimmune disease (pemphigus foliaceus) and an infection of ehrlichiosis caused by Ehrlichia canis were observed. Histopathological findings included signs of orthokeratotic hyperkeratosis, moderate follicular keratosis and light epidermic acanthosis. The reactive process included an infiltrative superficial dermatitis and a mural folliculitis with prevalent participation of macrophages and lymphocytes. The application of PCR-Restriction Enzyme Analysis (REA) method on cutaneous specimens in veterinary medicine is an extremely interesting diagnostic tool. Its use, together with other techniques, such as mycologic, cytologic and histological examinations, allowed us to identify Candida albicans as aetiological agent in this particular ...

Thyroid abnormalities and recurrent spontaneous abortion: diagnostic and therapeutical approach. AJRI 2000; 43:204-208 © Munksgaard, Copenhagen PROBLEM: The aim of this study is to evaluate the role of mild thyroid abnormalities in recurrent spontaneous abortion, and to assess the effects of two different therapeutical protocols. METHOD: A prospective study in the population of recurrent aborters with mild thyroid abnormalities, evaluating the obstetric outcome in 42 patients. Sixteen thyroid autoantibodies positive patients were treated with thyroid replacement therapy, while 11 patients received intravenous immunoglobulins (IVIG). Fifteen patients, characterized by negative antithyroid antibodies, and having underlying thyroid pathology, were treated with thyroid replacement therapy. RESULTS: Among patients with thyroid antibodies, 6 out of the 11 pregnancies (54.5%) treated with IVIG ended in live birth. In the thyroid supplementation group, 13 out of 16 pregnancies (81.2%) ended in live birth. Only one pregnancy loss occurred among patients with a mild underlying thyroid pathology treated with thyroid replacement therapy. CONCLUSIONS: Mild thyroid abnormalities are associated with an increased rate of miscarriage. This poor obstetrical prognosis seems to be related to an impaired thyroid adaptation to pregnancy. Thyroid replacement therapy appears to be more effective than IVIG in preventing a new miscarriage. * Our data, confirming that mild thyroid abnormalities are associated with increased risk of abortion, indicated that thyroid replacement therapy is more effective than IVIG in preventing new miscarriages in RSA patients with such pathologies.

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interac-tion between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97: 844-849)

The co-occurrence of autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) has been reported in individuals and families. In this study, the strength and nature of this association were investigated at the population level in a Swedish case-control cohort. Methods. For this case-control study, 1,419 patients with incident RA diagnosed between 1996 and 2003 were recruited from university, public, and private rheumatology units throughout Sweden; 1,674 matched control subjects were recruited from the Swedish national population registry. Sera from the subjects were tested for the presence of antibodies to cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and the 620W PTPN22 allele. Information on a history of diabetes was obtained by questionnaire, telephone interview, and/or medical record review. The prevalence of type 1 DM and type 2 DM was compared between patients with incident RA and control subjects and further stratified for the presence of anti-CCP, RF, and the PTPN22 risk allele. Results. Type 1 DM was associated with an increased risk of RA (odds ratio [OR] 4.9, 95% confidence interval [95% CI] 1.8-13.1), and this association was specific for anti-CCP-positive RA (OR 7.3, 95% CI 2.7-20.0), but not anti-CCP-negative RA. Further adjustment for the presence of PTPN22 attenuated the risk of anti-CCP-positive RA in patients with type 1 DM to an OR of 5.3 (95% CI 1.5-18.7). No association between RA and type 2 DM was observed. Conclusion. The association between type 1 DM and RA is specific for a particular RA subset, anti-CCPpositive RA. The risk of developing RA later in life in patients with type 1 DM may be attributed, in part, to the presence of the 620W PTPN22 allele, suggesting that this risk factor may represent a common pathway for the pathogenesis of these 2 diseases. Autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) have been observed to co-occur within individuals and families (1-4). Although the exact etiologies of RA and type 1 DM are unknown, they are likely attributable to a combination of genetic susceptibility and interactions between environmental risk factors and genes. Thus far, one established genetic risk factor is shared by RA and type 1 DM: the 620W allele of the protein tyrosine phosphatase N22 gene (PTPN22) (5-9). Other genes involved in the pathogenesis of RA and type 1 DM have

Several single nucleotide polymorphisms (SNPs) have been associated with susceptibility to autoimmune diseases, but the mechanisms responsible for the associations are poorly understood. To test the hypothesis that the variation of the basal levels of the gene products is significantly influenced by genetic polymorphism, we investigated whether SNPs in genes CD40, CD28, CTLA4, CD80, CD86, BAFF and IL6 are affecting mRNA or protein expression. The surface expression of the proteins on unstimulated monocytes,

The issue of adverse health effects from dental amalgam and the concurrent low-dose exposure to inorganic mercury have been scrutinized by several Swedish expert groups during the past years. Only rarely have amalgam fillings in children been related to health effects. Experimental studies in genetically disposed animals have shown that low doses of inorganic mercury can induce autoimmune glomerulonephritis. The present case-control study included 3 1 children with acute glomerulonephritis and 33 with Henoch-SchBnlein purpura retrieved from an in-patient register for the period 1973-1992 at the county hospital in Halmstad, Sweden. The median age was 10 and 9 years, respectively, for the two diagnostic groups. Dental clinics reported amalgam burden of the patients during the year before the date of diagnosis. Corresponding data were obtained for three randomly selected controls for each case, drawn from the case records of the same dental clinics, with matching for age and sex. Odds ratios (95% confidence interval) were 1.42 (0.49, 4.11) for Henoch-Schiinlein purpura, 0.59 (0.25, 1.38) for acute glomerulonephritis and 0.84 (0.40, 1.75) for both diseases combined. The results of this study did not indicate increased disease risk in relation to amalgam burden.

Few studies have compared gastrointestinal problems in children with an autism spectrum disorder with and without a history of language regression. A cross-sectional study was conducted with structured interviews in 100 children with autism spectrum disorder, using a gastrointestinal questionnaire and a familial autoimmune questionnaire. By parental report, children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%, P = 0.006) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%, P = 0.001) and of rheumatoid arthritis (30% vs 11%, P = 0.03). Among 35 children with a family history of autoimmune disease, an abnormal stool pattern was reported more frequently in those with language regression (78% vs 15%, P = 0.001) than in those without. An association was observed between children with language regression, a family history of autoimmune disease, and gastrointestinal symptoms. Additional studies are need...

Immunoglobulins have initially been illustrated as proteins produced by the immune system for binding and neutralizing foreign molecules potentially harmful to the organism. The number of V H , D H , J H , V L and J L genes that encode the variable regions of immunoglobulins and the junctional diversity that occurs at the time of somatic rearrangement determine the extent of the repertoire of antibodies that may be potentially produced by an organism. This potential repertoire includes antibodies the antigen binding site of which may recognize external as well as autologous antigens, or may structurally resemble the active site of enzymes and be endowed with enzymatic activity. Under physiological conditions, B cell clones that produce antibodies naturally endowed with catalytic activity are negatively regulated and subjected to apoptosis. Catalytic antibodies are expressed only following active immunization, or if the physiological regulatory mechanisms that control the expression of catalytic antibody-producing B cell clones are perturbed, e.g. in the context of pregnancy or in the course of autoimmune diseases.

Autoimmunity is believed to develop when genetically predisposed individuals encounter epigenetic modifications in response to environmental factors. Recent advances in the understanding of epigenetic mechanisms, their contribution to the immune function, and to the development of autoimmunity are presented in this special issue of Clinical Reviews in Allergy and Immunology. Potential new therapeutic strategies and biomarkers are also addressed.

Pregnant women with autoimmune neutropenia (AIN) and circulating neutrophil-specific autoantibodies can deliver neutropenic neonates at risk of sepsis. We report the case of a woman who had two such pregnancies. The woman had been on prophylactic granulocyte colony-stimulating factor (G-CSF) treatment, but this was ceased prior to conception in both pregnancies. In the first pregnancy, there was no monitoring or interventions, and the neonate was neutropenic and required intensive care treatment. In the second pregnancy, the maternal neutrophil autoantibody level was monitored, and G-CSF treatment was introduced in the third trimester. The second infant had no neutropenia at delivery and an excellent Apgar score. We discuss the management strategy in the second pregnancy that included monitoring of serial titres of the maternal autoantibody and the introduction of G-CSF in the third trimester, which may have contributed to a more favourable clinical outcome. This may assist other clinicians faced with similar dilemmas in the future.

In 2008, The ESC Working Group on Myocardial and Pericardial Diseases proposed an updated classification of cardiomyopathies based on morphological and functional phenotypes and subcategories of familial/genetic and non-familial/non-genetic disease. In this position statement, we propose a framework for the clinical approach to diagnosis in cardiomyopathies based on the recognition of diagnostic 'red flags' that can be used to guide rational selection of specialized tests including genetic analysis. The basic premise is that the adoption of a cardiomyopathy-specific mindset which combines conventional cardiological assessment with non-cardiac and molecular parameters increases diagnostic accuracy and thus improves advice and treatment for patients and families.

We now have substantial evidence demonstrating noradrenergic sympathetic and peptidergic innervation of both primary and secondary lymphoid organs. We have established criteria for norepinephrine, and some of the neuropeptides, as neurotransmitters, and have found changes in immune responsiveness following pharmacological manipulation of noradrenergic sympathetic or peptidergic nerves. Classic receptor binding studies have demonstrated a wide variety of target cells that possess/3-adrenoceptors and receptors for neuropeptides on cells of the immune system, including lymphocyte subsets, macrophages, accessory cells, or stromal elements. In this chapter we describe noradrenergic and peptidergic innervation of primary and secondary lymphoid organs in development, at maturation and during the normal aging process, and discuss possible functional implications of direct neural signals onto cells of the immune system at critical time points in the lifespan of an animal. Further, we examine for involvement of noradrenergic sympathetic and peptidergic innervation in the development and progression of several autoimmune disorders, including adjuvant-induced arthritis, New Zealand mice strains as a model for hemolytic anemia and lupus-like syndrome, and the experimental allergic encephalomyelitis model for multiple sclerosis.

Cardiovascular and neurological manifestations are known to occur in patients with autoimmune rheumatic disease (ARD), often in subclinical form. The term autonomic nervous system (ANS) describes nerves that are concerned predominantly with the regulation of bodily functions. It is comprised of sympathetic and parasympathetic nerves, and their function is complementary. ANS involvement has rarely been studied in patients with ARD, and studies have shown conflicting results. This may be because symptoms of autonomic dysfunction are nonspecific and extremely varied, and may pertain to several systems like the gastrointestinal, cardiovascular, and nervous. Moreover, tests to detect autonomic dysfunction are not routinely employed in clinical rheumatological practice. Another difficulty is to differentiate cardiovascular effects of drugs from ARD involvement. Previous studies on this topic found signs of parasympathetic and sympathetic dysfunction in variable proportions in patients with autoimmune diseases, between 24% and 100% in various tests depending on the methods used. Cardiovascular autonomic dysfunction is the most common type of ANS dysfunction, and was revealed in the majority of ARD patients.

The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60 min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back-muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. Back-muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back-muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD16- cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL-2) boosting of the NK cell activity was found during work as compared to IFN-alpha and indomethacin-enhanced NK cell activity. These results indicate that NK cells with a high IL-2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down-regulation of the NK cells.

Background: Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition.

, an article about septal ablation with alcohol for hypertrophic cardiomyopathy was published in the Journal. 1 The majority of those named as authors of the article did not have an opportunity to review and verify the data and to approve the manuscript. This unfortunate situation came to light when the article was published. In view of this irregularity in the submission process, we request that that paper be retracted. We believe that the alcohol-ablation technique described is a useful procedure in selected patients with hypertrophic cardiomyopathy, and other data support this view. 2,3 We also want to make clear that the Cleveland Clinic Foundation was not involved in the study but was mentioned purely as an address for correspondence. We hope that readers of the Journal will understand that this retraction is designed to maintain the integrity of the scientific process.

Antinuclear antibody (ANA) immunofluorescence tests, using HEp-2 cells, were performed on 100 children without a history of connective tissue disease. Eighteen (18%) were positive at titres greater than or equal to 1:40, nine (9%) being greater than 1:160. Interlaboratory variability was demonstrated with some specimens. No association with possible intercurrent infection was found to account for positive results. Of 44 children with proven infections five (11%) were positive. Antinuclear antibody may be found in some normal children when using the sensitive HEp-2 cell substrate, and in the absence of clinical features should not necessarily suggest the presence of a connective tissue disease.

Mesenchymal stem cells (MSCs) are now known to display not only stem cell multipotency, but also robust antiinfl ammatory and regenerative properties. After widespread in-vitro and in-vivo preclinical testing, autologous and allogeneic MSCs have been applied in a range of immune mediated conditions, including graft versus host disease, Crohn´s disease, multiple sclerosis, refractory systemic lupus erythematosus and systemic sclerosis. Current data suggests that MSCs may not only replace diseased tissues, but also exert several trophic, regenerative and antiinfl ammatory eff ects. While the clinical outcome in case reports and phase I-II trials seems occasionally striking, these limited results point to the need to perform controlled multicenter trials. Future advances from stem cell science can be expected to pinpoint signifi cant MSC subpopulations and/or stem cell markers for improved regenerative or immunoregulatory properties.

Patients with immunodeficiencies or some types of autoimmune diseases rely on a safe therapy with intravenous immunoglobulins (IVIGs) manufactured from human plasma, the only available source for this therapeutic. Since plasma is predisposed to contamination by a variety of blood-borne pathogens, ascertaining and ensuring the pathogen safety of plasma-derived therapeutics is a priority among manufacturers. Stateof-the-art manufacturing processes provide a high safety standard by incorporating virus elimination procedures into the manufacturing process. Based on their mechanism these procedures are grouped into three classes: partitioning, inactivation, and virusfiltration.

In the last year, different diseases possibly linked to Helicobacter pylori infection but localized outside of the stomach have been investigated. There are, in fact, several studies concerning cardiovascular diseases, hematologic disorders, neurologic diseases, metabolic, hepatobiliary diseases, and other conditions. Some of those studies, such as those on sideropenic anemia and idiopathic thrombocytopenic purpura, are quite large and well conducted, while in other cases there are just small or isolated studies or even case reports. Nonetheless, there is much interest among researchers all over the world for such a topic as demonstrated by the large number of studies published in the last year.

Patients with systemic autoimmune systemic disease who also have hair loss show lower quality of life (QOL) and mental health scores than patients without this cutaneous manifestation. Patients in remission from their global systemic disease are often left with alopecia, which significantly impairs their self-esteem and interferes with their personal and professional lives. This situation is often not adequately recognized, and withdrawal from social and work functions often leads to or augments long-standing depression in the patient. Our experience at a major tertiary referral center for the cutaneous manifestations of autoimmune disease suggests that once the systemic autoimmune disease is in remission, it is prudent to recognize the importance of alopecia in the patient's overall sense of well-being and QOL clinical outcome. LUPUS Hair loss is one of the most common cutaneous signs of systemic lupus erythematosus (SLE) and is present in more than half the patients at some time during the course of their illness. 1 Alopecia can be the presenting manifestation of SLE and may affect the scalp, eyebrows, eyelashes, beard hair, or body hair. 2 Alopecia may be associated with active disease and can also occur or be aggravated because of the medications used to treat lupus. Alopecia in lupus can be scarring, associated with chronic discoid lupus, or nonscarring, as is often seen in acute lupus. Overlapping components are frequently identified. The Systemic Lupus International Collaborating Clinics (SLICC) has recently recommended revision of the current American College of Rheumatology SLE classification criteria. 3 Discoid lupus had always been present in the most widely used classification criteria for SLE, including the SLICC classification criteria. However, nonscarring alopecia is again being suggested to be included in the newest revision as an individual criterion for SLE, as it was in the original 1971 American Rheumatism Association criteria. 4 Nonscarring Alopecia Nonscarring alopecia in lupus often develops during flares of acute systemic disease and can occur under multiple scenarios. One is telogen effluvium, which is a reactive process, not specific to lupus, characterized by a diffuse thinning of the scalp and

Human dihydroorotate dehydrogenase (hDHODH, EC 1.3.5.2), a flavindependent mitochondrial enzyme involved in de novo pyrimidine biosynthesis, is a validated therapeutic target for the treatment of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. However, human DHODH inhibitors have also been investigated as treatment for cancer, parasite infections (i.e. malaria) and viruses as well as in the agrochemicals industry. An overview of current knowledge of hDHODH inhibitors and their potential uses in diseases where hDHODH is involved. This review focuses on recent advances in the development and application of hDHODH inhibitors, specifically covering the patent field, starting from a brief description of enzyme topography and of the strategies usually followed in designing its selective inhibitors. The most important and well-described novelty is the fact that the discovery, in the autumn of 2016, that hDHODH inhibitors are able to induce in vivo myeloid differen...

A common feature of autoimmunity is the presence of autoantibodies (AAb). Two types of AAb have been described: the 'pathogenic' AAb, associated with autoimmune diseases (AID), and the so-called 'natural' AAb. The latter are present in all normal individuals and have been postulated to play a major role as a first defensive barrier of the organism. Both the 'pathogenic' and the 'natural' AAb can be detected at higher frequencies among individuals exposed to viral, bacterial and parasitic infections. The malaria associated AAb do not seem to result from a generalised polyclonal B-cell activation (PBA), have specificities that may differ according to the degree of clinical immunity and do not seem to be pathogenic. Malaria may offer a protective effect against AID, by diminishing its severity or by either preventing or retarding its expression. AAb could also participate in the immune protection against malaria, and this could happen in several ways: (i) AAb directed to modified Ag expressed on the red blood cell (RBC) membrane during parasitisation and (ii) AAb reactive with crypto-or neo-Ag revealed on both normal and infected RBC membranes, by destroying infected, and also normal, erythrocytes; (iii) anti-idiotype AAb specific of the binding site of anti-merozoite Ab, which would mimic the parasite ligand for the RBC receptor, by competing with parasites and blocking RBC invasion; (iv) AAb cross-reactive with parasite material -such as nuclear or cytoskeleton Ag -having a direct parasiticide activity; (v) the natural AAb network, through its 'anti-bacterial first defense barrier'; and finally (vi) anti-phospholipid (PL) AAb, by neutralizing the pathogenic properties of parasitederived PL. Finally, in view of currently available knowledge, it is concluded that, since AAb are not always pathogenic, the price for an 'autoimmunity-mediated' protection in malaria would not necessarily be immunopathology and clinical autoimmunity, and a protective role of AAb could be exerted with no danger to the host.

Anti-nuclear antibody (ANA) assay is a screening test used for almost all autoimmune rheumatic diseases, and in a number of these cases, it is a diagnostic/classification parameter. In addition, ANA is also a useful test for additional autoimmune disorders. The indirect immunofluorescence technique on monolayers of cultured epithelial cells is the current recommended method because it has higher sensitivity than solid phase assays. However, the technique is time-consuming and requires skilled operators. Automated ANA reading systems have recently been developed, which offer the advantage of faster and much easier performance as well as better harmonization in the interpretation of the results. Preliminary validation studies of these systems have given promising results in terms of analytical specificity and reproducibility. However, these techniques require further validation in clinical studies and need improvement in their recognition of mixed or less common staining patterns.

Background: Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition.

Immunoglobulin G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4-RD can occur in various organs, including the pancreas, lacrimal gland, salivary gland, thyroid, lung, bile duct, liver, gastrointestinal tract, kidney, prostate, retroperitoneum, arteries, lymph nodes, skin, and breast. Steroid therapy is often effective. In the field of neurology, pachymeningitis (IgG4-related pachymeningitis) and hypophysitis (IgG4-related hypophysitis) are known to be related to IgG4-RD. Recently, a few papers have described the involvement of peripheral nerves in IgG4-RD. Here, we describe the concept of IgG4-RD and highlight the involvement of the central and peripheral nervous systems in IgG4-RD.

Autoimmunity is a disease that occurs when the body tissue is attacked by its own immune system. Multiple sclerosis (MS) is an autoimmune illness which triggers neurological progressive and persistent functions. MS is associated with an abnormal B-cell response and upregulation of T-cell reactivity against a multitude of antigens. Mast cells are the first line of the innate immune system and act by de-granulating and secreting chemical mediators and cytokines. Their participation on the central nervous system has been recognized since the beginning of the last century. They have an important role in autoimmune disease, including MS where they mediate inflammation and demyelinization by presenting myelin antigens to T cells or disrupting the blood–brain barrier and permitting entry of inflammatory cells and cytokines. The participation of mast cells in MS is demonstrated by gene overexpression of chemical mediators and inflammatory cytokines. Here we report the relationship and involvement between mast cells and multiple sclerosis.

Chronic inflammation is a common feature shared by several autoimmune rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis, and ankylosing spondylitis. Therefore, blocking or reducing inflammation is one of the major treatment strategies in these diseases. In this context, exercise training has emerged as a potential therapeutic tool in counteracting systemic inflammation, thereby leading to better clinical outcomes. The aims of this review are i) to provide a summary of the clinical effects of exercise training in selected autoimmune rheumatic diseases; and ii) to discuss the potential anti-inflammatory role of exercise training in autoimmune rheumatic diseases, stressing the gaps in literature and the clinical and scientific perspectives in the field.

Introduction. -Les canaux K + permettent le passage passif et sélectif des ions K + au travers des membranes. Ils jouent un rôle majeur dans l'homéostasie du K + , dans le contrôle de l'excitabilité neuronale et musculaire et dans la sécrétion des neurotransmetteurs et des hormones.

Stranded between medicine and experimental biology, immunology is buried in its own problems and remains distant from important areas of current biology, such as evolutionary theory, developmental biology and cognitive sciences. Immunology has treated the living system merely as the place or dimension in which immune activity takes place, inserted on a misleading axis (progressive responsiveness versus no response; memory versus tolerance) which neglects the analysis of a robustly stable dynamics which is always present and is neither tolerance nor immunity-a problem currently approached as one of "regulatory" activity. However, a regulatory response also demands regulation, leading to an endless recursion and the adoption of a stimulus-response framework inevitably drives us away from the physiological processes in which lymphocytes are involved. Herein, we propose that immunological physiology, like everything else in the body is dynamic and conservative. Immunopathology, including inherited immunodeficiencies, severe forms of infectious diseases, allergy and autoimmune diseases, are interferences with this stability which frequently include oligoclonal expansions of T lymphocytes. We suggest that this decrease in clonal diversity results from a loss of the stabilizing connectivity among lymphocytes and are not simply markers of immunopathology, but are rather expressions of basic pathogenic mechanisms. The so-called autoimmune diseases are examples of this disequilibrium. In the last decade the characterization of an enormous and diversified commensal microbiota has posed a new and pressing problem: how to explain the harmonic conviviality with trillions of foreign macromolecules. In addition, robustly stable relations towards macromolecular diet can be established by simple ingestion, a state presently labeled as "oral tolerance", a problem that has been buffered for decades as anti-inflammatory protection of the gut. A major change in terminology is necessary to describe this new panorama. We focus on two important gaps in immunological discussions: (a) the organism, seen simultaneously as the medium with which the immune system is constantly in touch and as the entity that mediates the contact with external materials; and (b) the observer, the immunologist, who operates as a human being in human languaging with other human beings, and characterizes immunological specificity. We acknowledge that we are proposing radical departures from current dogma and that we should justify them. Most of what we propose stem form a way of seeing called Biology of Cognition and Language, that derives from ideas of the neurobiologist/ philosopher Humberto Maturana, also known as "autopoiesis theory".

Background: Alopecia areata (AA) is considered an autoimmune disease with undetermined pathogenesis. Age at onset predicts distinct outcomes. A nationwide study of the relationship of AA with associated diseases stratified by onset age has rarely been reported.