Autoimmunity

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 '...

Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.

The response to an uncontrolled spread of disease often incites a commingling of medical, moral, and political panic. Whether in the context of threats presented by early plagues, to contemporary super viruses, to lead toys, contagion, via transmission , makes interconnections visible, among and across peoples, cultures, objects, forms of commerce, and more. In this article, I use an intersectional disability studies framework to first discuss how, faced with the bio-insecurity of contagion, responses typically invoke discourses of war, empire, and what Priscilla Wald calls " medical nativism " (2008, 9). I then discuss how metaphors of autoimmunity often simply shift this discourse from concerns about external terror to that of internal terror (Sengupta 2014). Viewing autoimmunity from this vantage point, the body/nation is still viewed as vulnerable to attack, but the victim and the villain are the self/same. In the final section, I posit that a reimagined ethic of autoimmunity could offer new and fruitful ways to think about self/other relations that rely on mutual recognition and reject the binary, oppositional stance that undergirds annihilation. Keywords: autoimmunity / contagion / intersectional disability studies / metaphors of disease and illness / war metaphors

Przysługujący widmom wywrotowy, niemalże rewolucyjny potencjał został odsunięty oraz zagubiony poprzez pozbycie się tej kontrowersyjnej kategorii z terytorium metafizyki i zbyt pośpieszne odesłanie jej do przestrzeni badań nad literaturą, sprowadzając ją jedynie do roli użytecznego, bezpiecznego narzędzia interpretacji.

Książka Andrzeja Marca odzyskuje niepokojący charakter widmontologii i ponownie wprowadza widma do myśli metafizycznej. Czym nawiedzona i przeniknięta jest tradycyjna metafizyka, co właściwie ją dręczy, nie daje spokoju oraz nieustannie podmywa jej stabilność?

Kategoria widma Derridy posłużyła Marcowi przede wszystkim do rozważań nad charakterem współczesności i przeobrażeń, jakie dokonały się w obrębie myśli ponowoczesnej. Współczesna kultura, zdaniem Marca, stała się miejscem powstawania widm, nieustannie powracających z przeszłości. Uznając, że nie jesteśmy już w stanie tworzyć utopijnych wizji przyszłości, autor stara się zdać sprawę z widmowego charakteru współczesnej kultury, analizując m. in. strategie vintage, retro, nurt no future w kulturze lat 70. czy nurt fantastyki naukowej w literaturze.

“Power is war, the continuation of war by other means”: Foucault’s reversal of Clausewitz’s formula has become a staple of critical theory — but it remains highly problematic on a conceptual level. Elaborated during Foucault’s 1976 lectures (“Society Must Be Defended”), this work-hypothesis theorises “basic warfare” [la guerre fondamentale] as the teleological horizon of socio-political relations. Following Boulainvilliers, Foucault champions this polemological approach, conceived as a purely descriptive discourse on “real” politics and war, against the philosophico-juridical conceptuality attached to liberal society (Hobbes’s Leviathan being here the prime example).
However, in doing so, Foucault did not interrogate the conceptual validity of notions such as power and war, therefore interlinking them without questioning their ontological status. This problematic conflation was partly rectified in 1982, as Foucault proposed a more dynamic definition of power relations: “actions over potential actions”.
I argue, somewhat polemically, that Foucault’s hermeneutics of power still involves a teleological violence, dependent on a polemological representation of human relations as essentially instrumental: this resembles what Derrida names, in “Heidegger’s Ear”, an “anthropolemology”. However, I show that all conceptualisation of power implies its self-deconstruction. This self-deconstructive (or autoimmune) structure supposes an archi-originary unpower prior to power: power presupposes an excess within power, an excessive force, another violence making it both possible and impossible. There is something within power located “beyond the power principle” (Derrida). This (self-)excess signifies a limitless resistantiality co-extensive with power-relationality. It also allows the reversal of pólemos into its opposite, as unpower opens politics and warfare to the messianic call of a pre-political, pre-ontological disruption: the archi-originary force of différance. This force, unconditional, challenges Foucault’s conceptualisations of power, suggesting an originary performativity located before or beyond hermeneutics of power-knowledge, disrupting theoreticity as well as empiricity by pointing to their ontological complicity.
The bulk of this essay is dedicated to sketching the theoretical implications of this deconstructive reading of Foucault with respect to the methodology and conceptuality of political science and social theory.

Antibodies against nucleosomes are a serological hallmark of systemic lupus erythematosus (SLE). Apoptotic cells are the unique source of nucleosomes, which are formed through cleavage of chromatin by nucleases. These nucleosomes and other autoantigens targeted in SLE are expressed in apoptotic blebs or at the surface of apoptotic cells. Therefore, it is conceivable that circulating antibodies can influence apoptotic cell clearance. Using an in vitro phagocytosis assay, we analysed the phagocytic efficacy for apoptotic cells of resident peritoneal macrophages from pre-morbid and diseased lupus mice. The assay was carried out in the presence of autologous serum, using autologous apoptotic thymocytes as targets. Under these conditions macrophages from diseased MRL/lpr and NZB NZW(F1) lupus mice, and from age-matched NZB mice showed a decreased phagocytic efficacy (decrease 47%, 48% and 37%, respectively compared to measurements in pre-morbid mice). The cause of this decrease resides in the serum, and is not due to an acquired defect of macrophages. In conclusion, during disease progression in murine SLE, apoptotic cell clearance becomes impaired, which might amplify further disease progression.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that share some symptoms such as muscular weakness and inflammation of skeletal muscle. Complete recovery of muscle function with pharmacological treatment does not always occur, suggesting that physical inability is a great concern for these patients. In this context, it has been speculated that physical exercise could result in functional benefits to patients with IIM, leading to an improvement in quality of life. In fact, recent studies of polymyositis (PM) and dermatomyositis (DM) support the notion that exercise training improves or at least stabilizes muscle strength and functional ability without inducing disease flares. Importantly, these benefits were observed not only during the chronic phase, but also in the course of active disease. This positive effect was found to be long term, as demonstrated by a six-month significant improvement in exercise capacity and strength. Together, these findings indicate that a well controlled exercise program can be recommended for patients with DM and PM. The optimal exercise modality training and the underlying mechanism for this encouraging response remain to be determined in future studies.

Multiple sclerosis (MS) is a CNS-demyelinating disease characterised by relapsing and chronic neurological impairment. While traditionally CNS autoantigen-specific CD4+ T cells have been considered the culprits in the initial phase of the disease, recent observations have altered this concept. It is now recognised that other T lymphocyte subclasses can initiate CNS demyelination. In addition, other cell types and molecules may play an important role in MS pathogenesis. There is overwhelming evidence that MS is a dynamic process, in which recurrent episodes of blood–brain barrier disruption and CNS inflammation play a crucial role in early disease stages, leading eventually to the largely irreversible changes of demyelination, gliosis and axonal degeneration. These observations may have important therapeutic implications. Within the last ten years, several medications have been approved for MS treatment. These agents, all of which are given parenterally, are only partially effective and are often associated with adverse effects and potential toxicities. The number and different types of medications used for MS are likely to increase in the near future, as several novel therapies are currently tested in clinical trials. 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors, ‘statins’, are cholesterol-lowering drugs that are given orally, are safe and have biological effects independent of their cholesterol-reducing properties. Recent reports have shown that statins have anti-inflammatory and neuroprotective properties that may be beneficial in the treatment of MS. This article will outline experimental evidence that suggests potential clinical benefits of statins for MS patients.

Sjogren's syndrome (SS) is an exocrinopathy characterized by T cell infiltrates, salivary gland epithelial cell (SGEC) apoptosis and high Fas and FasL expression. To address the participation of T cell-derived cytokines and of Fas apoptotic pathway in SS glandular lesions, we utilized non-neoplastic SGEC lines established from SS patients and controls. Possibly attesting to their intrinsic activation, cell lines derived from SS patients displayed significantly higher constitutive Fas and FasL than controls. Surface co-expression of Fas and FasL was not associated with spontaneous fratricide apoptosis. SGEC were resistant to anti-Fas-mediated apoptosis (possibly owing to the constitutive expression of anti-apoptotic proteins cFLIP and Bcl-2), but became sensitive after protein or RNA synthesis inhibition. IFN-and TNF-were able to upregulate surface Fas and FasL, whereas IL-1 downregulated surface FasL. IFN-(but not several other cytokines) reduced the survival of SGEC in a dose-and time-dependent manner and induced Fas/FasL-mediated apoptosis, directly and via anoikia. Dexamethasone inhibited the upregulation of Fas and FasL by IFN-and the induction of SGEC apoptosis and detachment by anti-Fas mAb or IFN-. Our findings indicate the injurious role of IFN-for the salivary epithelia of SS patients through the induction of Fas-mediated apoptosis and anoikia.

Insulin dependent diabetes mellitus (type I DM) is caused by an autoimmune process which culminates in destruction of pancreatic beta cells with resultant loss of insulin production. Preceding the clinical diagnosis of type I DM is a preclinical stage characterized by autoantibodies to insulin, glutamic acid decarboxylase (GAD) and a tyrosine phosphatase-like molecule (IA-2). We have studied both HLA class I and class 2 allele distributions in diabetic probands and autoantibody positive individuals in members of 452 families recruited for the Australian type I diabetes DNA repository. The results demonstrate that progression to autoimmunity as measured by the appearance of autoantibodies is strongly associated with the class 2 alleles DRB1*03 and DRB*04 and with DRB1*03/04 heterozygosity. In contrast, the progression to clinical disease appears associated with class I alleles A24, A30 and B18 while A1, A28, B14 and B56 appear negatively associated. The class 2 alleles appear to have a minimal role in the progression from autoantibody positivity to clinical disease. These results are consistent with the view that CD4 þ T cells responding to peptides in the context of class 2 molecules are responsible for initiating autoantibody production, while the destruction of islet cells leading to clinical expression of the disease is the function of CD8 þ T cells recognizing relevant peptides in the context of class I molecules.

In patients given a diagnosis of chronic spontaneous urticaria (CSU), there are no obvious external triggers, and the factors that initiate the clinical symptoms of wheal, flare, and itch arise from within the patient. Most patients with CSU have an autoimmune cause: some patients produce IgE autoantibodies against autoantigens, such as thyroperoxidase or double-stranded DNA, whereas other patients make IgG autoantibodies against FcεRI, IgE, or both, which might chronically activate mast cells and basophils. In the remainder of patients with CSU, the nature of the abnormalities has not yet been identified. Accumulating evidence has shown that IgE, by binding to FcεRI on mast cells without FcεRI cross-linking, can promote the proliferation and survival of mast cells and thus maintain and expand the pool of mast cells. IgE and FcεRI engagement can also decrease the release threshold of mast cells and increase their sensitivity to various stimuli through either FcεRI or other receptors...

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.

We experienced the case of a 3-year-old male with a very rare combination of autoimmunity, including immune thrombocytopenia, recurrent Henoch-Schönlein purpura and intestinal Behçet disease. Exome sequencing of the patient's peripheral blood mononuclear cells identified a KRAS G13C mutation. Interestingly, the KRAS G13C mutation was observed in T and B lymphocytes, as well as natural killer cells, but not granulocytes. Our case was completely phenotypically different from RASopathies and did not meet the criteria for Ras-associated lymphoproliferative disease or juvenile myelomonocytic leukemia. This is the first reported case in which the KRAS mutation existed only in the lymphoid lineage. Based on the findings of our case and the current literature, it is clear that the RAS mutation in lymphoid cells is tightly linked with various autoimmune symptoms. The presence of the RAS mutation in lymphocytes should be reconsidered as a pathogenesis in cases of autoimmunity.

PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription factor autoimmune regulator (AIRE) to promote central T-cell tolerance. We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity associated with decreasing T- and B-cell counts over time that had been diagnosed in 2 unrelated patients. Genetic, molecular, and functional analyses were performed to characterize an inflammatory disease evocative of a combined immunodeficiency. We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA double-strand break repair and V(D)J recombination. Whole-blood mRNA analysis revealed a strong interferon signature. On activation, memory T cells displayed a skewed cytokine response typical of TH2 and TH1 but not TH...

Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls (P < 0.001). Increased serum osteopontin levels were found in 80.95% (34/42) of autistic children. Children with severe autism had significantly higher serum osteopontin levels than patients with mild to moderate autism (P = 0.02). Moreover, serum osteopontin levels of autistic patients had significant positive correlations with CARS (P = 0.007). In conclusions, serum osteopontin levels were increased in many autistic children and they were significantly correlated to the severity of autism. Further wide-scale studies are warranted to shed light on the etiopathogenic role of osteopontin in autism and to investigate its relation to IL-17 and brain-specific auto-antibodies, which are indicators of autoimmunity, in these patients. The therapeutic role of anti-osteopontin antibodies in amelioration of autistic manifestations should also be studied.

Western blotting with U937 cell extracts as the substrate, and enzyme-linked immunosorbent assays (ELISA) with U937-, Jurkat-and Daudi cell-purified CD45 molecules were used to detect anti-CD45 reactivity in patients with systemic lupus erythematosus (SLE). By immunoblotting, 16 of 64 SLE sera were shown to be positive (25.0%). In the ELISAs, 13 out of 18 SLE sera reacted with the target CD45. Of these, three were not detectable on the blot. Importantly, 12 of these ELISA-positive sera contained IgM and IgG autoantibodies. Neuraminidase-treatment of U937-precipitated CD45 molecules enhanced the reactivity to most of the isoforms, indicating that the antibodies may bind to asialylated polysaccharides.

The folk admonition to “starve a fever” may have a scientific basis. Fevers due to infectious organisms that produce neuraminidase (sialidase) may contribute to the pathophysiology of autoimmune conditions. Neuraminidase unmasks host cellular lectins that interact with food lectins and can induce human leukocyte antigen type II (HLA II) expression. HLA II can then bind food lectins and serve as targets for antibody production. Some of these antibodies can then cross-react and attack healthy tissue, inducing disease. The example of insulin-dependent diabetes mellitus is discussed, helping to explain why infectious organisms and dairy product ingestion appear to be linked to some cases of this disease. Genetic variants and other factors may contribute to disease pathogenesis, so this model does not explain all instances of autoimmune disease. Fasting as a way to avoid the process by not introducing food lectins is briefly reviewed. Neuraminidase inhibitors might be useful in preventing genesis of autoimmunity during infection, although this possibility has not been formally tested.

Background
Anemia is a common blood condition that affects populations in both rich and poor countries.  The most prevalent anemia after iron deficiency anemia is the anemia of chronic disease. It is usually observed as a non-specific anemia in patients with infectious, inflammatory and neoplastic diseases, and may cause diagnostic challenges. Routine diagnostic tests are performed in these patients, but recently, new blood markers such as hepcidin antimicrobial peptide are used to evaluate the severity of the disease. 

Objective
To evaluate the association between inflammatory disease and the potential risk for anemia in pediatric age-groups.

Methods and materials
In this study were involved 64 children aged 0 to 18 years old, hospitalized in ‘’Pediatric Service’’, the University Medical Center of Tirana “Mother Teresa”, during May 2018. Patients were diagnosed with diseases associated with the inflammatory process. Complete blood count (CBC) tests and other tests that detect inflammation such as C-Reactive Protein and Erythrocyte Sedimentation Rate (CRP and ESR), were determined in patients with hemoglobin (Hb)  levels < 11.5 g/dl. The CBC parameters are measured using Automated Cell Counter machines, ESR is measured using Westergren method, CRP test is based on the principle of the latex agglutination, and the colorimetric method is used for serum iron measurement. All the cases involved in this study were evaluated other examinations and laboratory tests, which were significant in the determination of the diagnosis.

Results
The average age of patients included in the study was 2.65 years old among which 56.25%  were male and 44.75% were female. 12.5% of patients had blood malignancies, 34.4% had acute bacterial diseases, 18.7% had chronic bacterial diseases, 23.4% had viral infections and 10.9% had autoimmune diseases. Patients with chronic bacterial diseases and viral infections had significantly higher levels of ESR (ESR=29.83, N=0-13mm/h) than others. Levels of CRP were higher in patients with acute bacterial diseases (CRP=52.84, N=3-20mg/dl), and the levels of hemoglobin were lower in patients with autoimmune diseases (Hb=9.14, N=13-16 ±2 mg/dl). This was presented with a high variance in the values of ESR (σ^2 = 286.09) and  CRP ( σ^2= 2002.28). The evaluations revealed a moderate positive correlation between Hb and RBC (R^2=0.15), a mild negative correlation between Hb and ESR, also between Hb and CRP.



Conclusion
The time span and the degree of the inflammation which coexists with the underlying disease, determine the type of anemia which associates them. These results suggest that in this pediatric age-group, the treatment should focus on the underlying disease in order to correct anemia.

Keywords
anemia, inflammation, pediatric age-group, hemoglobin, CRP, ESR, iron metabolism.

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.

Autoimmune inner ear disease probably accounts for less than 1% of all cases of balance disorders, but its incidence is often overlooked due to the absence of a speciWc diagnostic test. Furthermore, in several systemic autoimmune diseases the vestibulo-cochlear system may be aVected. Clinical features comprise generalized imbalance, ataxia, motion intolerance, episodic vertigo and positional vertigo. An autoimmune mechanism seems to be responsible for 6% of unilateral and 16% of bilateral forms of Ménière's disease. Oscillopsia and disequilibrium secondary to a bilateral vestibular paresis are probably caused by an autoimmune response in 5% of cases. Balance disorders of central origin may be due to other immuno-mediated disorders such as multiple sclerosis, brainstem encephalitis and vasculitidis. Aim of this paper is to assess the clinical features of autoimmune vertigo disorders through a systematic literature review.

Rasmussen encephalitis (RE) is a rare but severe immunemediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction and intractable seizures. Recent data on the pathogenesis of the disease, its clinical and paraclinical presentation, and therapeutic approaches are summarized. Based on these data, we propose formal diagnostic criteria and a therapeutic pathway for the management of RE patients.

The human B cell survival factor, B cell activation factor (BAFF), and its closely related homologue, a proliferation-inducing ligand (APRIL), modulate B cell functions by binding to three receptors, BAFFR, TACI and BCMA. APRIL binds more strongly to BCMA than to TACI while the opposite is true for BAFF.  In addition, BAFF, but not APRIL, binds to BAFF-R with high affinity.  Both BAFF and APRIL are known to form homotrimers and heterotrimers, which display different affinities for their cognate receptors.  To understand the structural basis underlying the different binding affinities, we solved the crystal structure of the APRIL-BAFF-BAFF heterotrimer, either alone or bound to TACI.  Analysis of these structures and comparative analysis of previously solved structures of BAFF and APRIL in complex with BAFFR, TACI or BCMA revealed that the charged residues of BAFF and APRIL are crucial determinants of receptor binding affinities, conferring homotrimers and heterotrimers with a variety of signaling strength to modulate responses of immune cells.

Food allergies and intolerance represent important health concerns to consumers who are predisposed to these illnesses. Unlike many current food safety issues, food sensitivities are complicated by both complex and multiple individual adverse reactions, which can vary from emotional to pathophysiological ailments. In some instances, the underlying mechanisms that result in the development of food allergies or intolerance have marked differences but produce common symptoms. The present-day diagnosis of these disorders can be impeded by intrinsic limitations in generating accurate information from patient history and biochemical, physicochemical, and immunochemical tests. Oral challenge tests represent effective methods for confirming and testing food allergens and food intolerance; however, these procedures are often restricted to clinical trials. It is important to be able to distinguish among food allergy, intolerance, and autoimmune disease in the management of these disorders. The role of food in the development of autoimmune disease may be exemplified by celiac disease, a food-induced enteropathy, requiring exposure to prolamins in wheat, rye, and barley. Various wheat and soy protein sources, including the soy protein isolates used to make infant formulas, have been related to juvenile or insulin-dependent diabetes mellitus (IDDM), a common chronic disease of childhood. Employing food process technologies to eliminate food constituents with potential for intolerance in some individuals is a potentially viable approach for reducing risk to food-related disorders. Finally, the development of food labelling regulations that require the identification of potential food allergens or agents for intolerance in the ingredient declaration on prepackaged food is a positive step toward the prevention of severe adverse reactions in hypersensitive individuals.

The neo-epitope tTg (tTg-neo) autoantibody, never challenged the anti-tissue transglutaminase (tTg) premier-ship, recommended by ESPGHAN, for celiac disease (CD) diagnosis. Pediatric CD (PCD), abdominal pains and normal children, normal adults, and rheumatoid arthritis patients, were tested using the following ELISAs detecting IgA, IgG or both IgA and IgG (check): AESKULISA® tTg (tTg; RUO) and AESKULISA® tTg-neo. Higher OD activity was detected for tTg-neo IgA, IgG and IgA + IgG than for tTg. tTg-neo IgA, IgG correlated better with intestinal damage than tTg. The tTg-neo combined IgA + IgG ELISA kit had higher sensitivity and a comparable specificity for the diagnosis of PCD. The drop in the % competition was much higher with the tTg-neo then the tTg antibodies. The false positivity of the tTg was significantly higher than the tTg-neo one. Serological diagnostic performances, reflection of intestinal damage, diverse epitopes and false positivity were better with the tTg-neo.

Recently, a group of experts in the field suggested to rename ChurgeStrauss syndrome as eosinophilic granulomatosis with polyangiitis (EGPA). This condition, first described in 1951, is a rare small-and medium-sizedevessel vasculitis characterized by an almost constant association with asthma and eosinophilia, and, by the presence of anti-myeloperoxidase (MPO) antineutrophil cytoplasm antibodies (ANCA) in 30e38% of the patients. Vasculitis typically develops in a previously asthmatic and eosinophilic middle-aged patient. Asthma is severe, associated with eosinophilia and extrapulmonary symptoms. Most frequently EGPA involves the peripheral nerves and skin. Other organs, however, may be affected and must be screened for vasculitis, especially those associated with a poorer prognosis, such as the heart, kidney and gastrointestinal tract, as assessed by the recently revised Five-Factor Score (FFS). Recent insights, particularly concerning clinical differences associated with ANCA status, showed that EGPA patients might constitute a heterogeneous group. Thus, EGPA patients with anti-MPO ANCA suffered more, albeit not exclusively, from vasculitis symptoms, such as glomerulonephritis, mononeuritis multiplex and alveolar hemorrhage, whereas ANCA-negative patients more frequently develop heart involvement. This observation led to the hypothesis that EGPA might be divided into different clinical and pathophysiological subtypes, which could be managed better with more specifically adapted therapies.

The critical function of the immune system is to discriminate self from non-self. Tolerance against self-antigens is a highly regulated process and, in order to maintain it, the immune system must be able to distinguish selfreactive lymphocytes as they develop. The presence of autoantibodies is the consequence of breakdown of tolerance and, although they are an important serological feature of autoimmune diseases, their presence is not exclusive of these conditions. Antibodies against self-antigens are also found in cancer, during massive tissue damage and even in healthy subjects. Natural autoantibodies provide immediate protection against infection and also prevent inflammation by facilitating the clearance of oxidized lipids, oxidized proteins, and apoptotic cells; their role in development of autoimmunity is still unclear. Detection of serum autoantibodies in clinical practice has become more available to clinicians worldwide while providing a powerful diagnostic tool. This review discusses the clinical significance of autoantibodies, their pathogenic mechanisms in autoimmune diseases and, finally, illustrates the technology available for appropriate autoantibody detection.

In this short article, I discuss a form of civil disobedience that emerged during the Covid-19 pandemic: the refusal to comply with lockdown rules. Because such rule-breakers often claim that they are acting to preserve freedom, I ask whether their unwillingness to help prevent the spread of the virus is symptomatic of neoliberal individualism. Drawing on Jacques Derrida's work on autoimmunity, I argue that Covid disobedience is ironically self-defeating, because in exacerbating the crisis the rule-breakers force governments to adopt increasingly draconian measures. Lockdown-refusers evidently believe that the protection of their individual rights is more important than the protection of vulnerable members of society, but this is an illusion. The self-sufficiency that they presuppose is a myth that sustains liberalism, and which has been debunked by the interdependency that the pandemic reveals.

Putting the question of the long development and inheritance of immune functions (phylogenesis) in touch with that of cultural inheritance (epiphylogenesis), the article questions lines of continuity between somatic mutation, consciousness, technics, time, and media. For instance, drawing on a tradition that acknowledges Immanuel Kant, Edmund Husserl, Theodor Adorno, and Martin Heidegger, Bernard Stiegler’s attempt to mobilize the structure of the trace in the philosophy of Jacques Derrida results in a profound challenge to a technics that can be regarded as a powerful complement to biological evolutionary inheritance.

Fibromyalgia syndrome (FMS) is a condition of chronic muscle pain and fatigue of unknown etiology and pathogenesis. There is limited support for the various hypotheses espoused to account for the manifestations of FMS, including immunogenic, endocrine, and neurological mechanisms. Treatment, partially effective at best, is directed toward symptomatic relief without the benefit of targeting known, underlying pathology. A noteworthy commonality among partially effective therapies is a vasodilatory effect. This is true both of conventional treatments, unconventional treatments such as intravenous micronutrient therapy, and lifestyle treatments, specifically graduated exercise. The pain of fibromyalgia is described in terms suggestive of the pain in muscles following extreme exertion and anaerobic metabolism. Taken together, these characteristics suggest that the pain could be induced by vasomotor dysregulation, and vasoconstriction in muscle, leading to low-level ischemia and its metabolic sequelae. Vasodilatory influences, including physical activity, relieve the pain of FMS by increasing muscle perfusion. There are some preliminary data consistent with this hypothesis, and nothing known about FMS that refutes it. The hypothesis that the downstream cause of FMS symptoms is muscle hypoperfusion due to regional vasomotor dysregulation has clear implications for treatment; is testable with current technology; and should be investigated.

Angioedema due to an acquired deficiency in the inhibitor of the first component of human complement (CI-INH) is a rare syndrome that is usually identified as acquired angioedema (AAE). The clinical features of C1-INH deficiency, which may also be of genetic origin (hereditary angioedema, HAE), include subcutaneous, non-pruritic swelling, involvement of the upper respiratory tract, and abdominal pain due to partial obstruction of the gastrointestinal tract. Unlike those with HAE, AAE patients have no family history of angioedema and are characterised by the late onset of symptoms and various responses to treatment due to the hypercatabolism of C1-INH. The reduction in C1-INH function leads to activation of the classical complement pathway and complement consumption, as well as activation of the contact system leading to the generation of the vasoactive peptide bradykinin, increased vascular permeability, and angioedema. AAE is frequently associated with lymphoproliferative diseases ranging from monoclonal gammopathies of uncertain significance (MGUS) to non-Hodgkin's lymphoma (NHL) and/or anti-C1-INH inactivating autoantibodies. The coexistence of true B cell malignancy, non-malignant B cell proliferation and pathogenic autoimmune responses suggests that AAE patients are all affected by altered B cell proliferation control although their clinical evolution may vary.

Objective. To investigate the effect of the fermented wheat germ extract (Avemar ® ) in patients with severe rheumatoid arthritis (RA). Methods. Fifteen female RA (Steinbrocker II-III) patients, who had unsuccesfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received Avemar ® as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used. Results. At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of Avemar ® were observed. Conclusion. Supplementation of standard therapies with a continuous administration of Avemar ® is beneficial for RA patients.