La sindrome “Cefalea e deficit neurologici transitori con linfocitosi liquorale”: un’altra encefalopatia autoimmune?

Headache and neurologic deficits with cerebrospinal fluid lymphocytosis syndrome (HaNDL) is a rare nosographic entity, which mainly affects adults but can also occur in the paediatric age. In the literature, 31 cases in this age group are described. Symptomatology typically lasts about three months with episodes that tend to relapse. An autoimmune pathogenesis has been hypothesized. The paper describes the case of an adolescent who presented with three acute and transient episodes of migraine headache in three days associated with impaired consciousness, focal neurological deficits and CSF lymphocytosis. After treatment with steroidal and non-steroidal anti-inflammatory drugs, the patient did not relapse in the following four months. The treatment indicated in the literature is only supportive (analgesics, antiemetics), however in this case the anti-inflammatory therapy reduced the duration of the episode and the recurrence of further episodes.

Myeloradiculitis with lupus-like autoimmunity following Sinovac COVID-19 vaccination

We report a 67 year old man with features in keeping with transverse myelitis, lumbar root and cauda equina involvement suggestive of delayed autoimmune pathogenesis after the Sinovac COVID-19 vaccination previously observed in vaccines containing viral antigens. Grossly elevated antinuclear antibody and anti-double-stranded DNA are in line with observations in lupus myelitis despite the lack of systemic manifestations.

An Update on Targeted Treatment of IgA Nephropathy: An Autoimmune Perspective

Immunoglobulin (Ig) A nephropathy (IgAN) is the commonest form of primary glomerulonephritis worldwide and is, considered a significant cause of end-stage renal disease in young adults. The precise pathogenesis of IgAN is unclear. The clinical and pathological features vary significantly between individuals and races, which makes treating IgAN difficult. Currently, the therapeutic strategies in IgAN are still optimal blood pressure control and proteinuria remission to improve the renal function in most cases. Immunosuppressive drugs such as corticosteroids can be considered in patients with persistent proteinuria and a high risk of renal function decline; however, they include a high toxicity profile. Therefore, the safety and selectivity of medications are critical concerns in the treatment of IgAN. Various pharmacological therapeutic targets have emerged based on the evolving understanding of the autoimmune pathogenesis of IgAN, which involves the immune response, mucosal immunity, renal inflammation, complement activation, and autophagy; treatments based on these mechanisms have been explored in preclinical and clinical studies. This review summarizes the progress concerning targeted therapeutic strategies and the relevant autoimmune pathogenesis in IgAN.

Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called “post-COVID syndrome” or “long-COVID” [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups. Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.

Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis

Interleukin-17E (IL-25) is a member of the IL-17 cytokine family that includes IL-17A to IL-17F. IL-17 family cytokines play a key role in host defense responses and inflammatory diseases. Compared with other IL-17 cytokine family members, IL-25 has relatively low sequence similarity to IL-17A and exhibits a distinct function from other IL-17 cytokines. IL-25 binds to its receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor B (IL-17RB) for signal transduction. IL-25 has been implicated as a type 2 cytokine and can induce the production of IL-4, IL-5 and IL-13, which in turn inhibits the differentiation of T helper (Th) 17. In addition to its anti-inflammatory properties, IL-25 also exhibits a pro-inflammatory effect in the pathogenesis of Th17-dominated diseases. Here, we review recent advances in the roles of IL-25 in the pathogenesis of inflammation and autoimmune diseases.

Milestones in Personalized Medicine in Pemphigus and Pemphigoid

Pemphigus and pemphigoid diseases are autoimmune bullous diseases characterized and caused by autoantibodies targeting adhesion molecules in the skin and/or mucous membranes. Personalized medicine is a new medical model that separates patients into different groups and aims to tailor medical decisions, practices, and interventions based on the individual patient`s predicted response or risk factors. An important milestone in personalized medicine in pemphigus and pemphigoid was achieved by verifying the autoimmune pathogenesis underlying these diseases, as well as by identifying and cloning several pemphigus/pemphigoid autoantigens. The latter has become the basis of the current, molecular-based diagnosis that allows the differentiation of about a dozen pemphigus and pemphigoid entities. The importance of autoantigen-identification in pemphigus/pemphigoid is further highlighted by the emergence of autoantigen-specific B cell depleting strategies. To achieve this goal, the chimeric antigen receptor (CAR) T cell technology, which is used for the treatment of certain hematological malignancies, was adopted, by generating chimeric autoantigen receptor (CAAR) T cells. In addition to these more basic science-driven milestones in personalized medicine in pemphigus and pemphigoid, careful clinical observation and epidemiology are again contributing to personalized medicine. The identification of clearly distinct clinical phenotypes in pemphigoid like the non-inflammatory and gliptin-associated bullous pemphigoid embodies a prominent instance of the latter. We here review these exciting developments in basic, translational, clinical, and epidemiological research in pemphigus and pemphigoid. Overall, we hereby aim to attract more researchers and clinicians to this highly interesting and dynamic field of research.

Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State

Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, with its paracellular tight junctions, to maintain the balance, tolerance, and resistance to foreign/neo-antigens. The physiological regulator of paracellular tight junctions plays a vital role in transferring macromolecules across the intestinal barrier and thereby maintains immune response equilibrium. A new paradigm has explained the intricacies of disease development and proposed that the processes can be prevented if the interaction between the genetic factor and environmental causes is barred by re-instituting the intestinal wall function. The latest clinical evidence and animal models reinforce this current thought and offer the basis for innovative methodologies to thwart and treat autoimmune syndromes.