The Role of HLA in the Association between IgA Deficiency and Celiac Disease

Selective IgA deficiency (SIgAD) is the most frequent primary immune defect. Since SIgAD is not characterized by relevant infectious issues in most cases, it is often diagnosed during the diagnostic work up of several and different autoimmune disorders, which are associated with this primary immune defect. The genetic background of SIgAD is complex and three HLA haplotypes resulted to be more frequently associated with it; in detail, two of them include HLA-DQB 1 ∗ 02 allelic variants, which are essential predisposing factors to develop Celiac Disease (CD). Here, we discuss the evidence regarding the role of HLA in the etiopathogenesis of SIgAD and its association with CD. Actually, the HLA region seems to play a modest role in the genetic predisposition to SIgAD and we may speculate that the association with the HLA-DQB 1 ∗ 02 alleles (or haplotypes including them) could derive from its link with CD. Indeed, SIgAD and some related immunological alterations are likely to predispose to several autoimmune diseases (with and despite different HLA backgrounds), including CD, which is relatively common and directly associated with the HLA-DQB 1 ∗ 02 allelic variants coding the DQ2 heterodimer. Further and specific studies are needed to make final conclusions in this regard.

Long COVID a New Derivative in the Chaos of SARS-CoV-2 Infection: The Emergent Pandemic?

Coronavirus disease 2019 (COVID-19) is a multisystem illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can manifest with a multitude of symptoms in the setting of end-organ damage, though it is predominantly respiratory. However, various symptoms may remain after acute SARS-CoV-2 infection, and this condition is referred to as “Long COVID” (LC). Patients with LC may develop multi-organ symptom complex that remains 4–12 weeks after the acute phase of illness, with symptoms intermittently persisting over time. The main symptoms are fatigue, post-exertional malaise, cognitive dysfunction, and limitation of functional capacity. Pediatric patients developed the main symptoms of LC like those described in adults, although there may be variable presentations of LC in children. The underlying mechanisms of LC are not clearly known, although they may involve pathophysiological changes generated by virus persistence, immunological alterations secondary to virus–host interaction, tissue damage of inflammatory origin and hyperactivation of coagulation. Risk factors for developing LC would be female sex, more than five early symptoms, early dyspnea, previous psychiatric disorders, and alterations in immunological, inflammatory and coagulation parameters. There is currently no specific treatment for LC, but it could include pharmacological treatments to treat symptoms, supplements to restore nutritional, metabolic, and gut flora balance, and functional treatments for the most disabling symptoms. In summary, this study aims to show the scientific community the current knowledge of LC.

Headache and immunological/autoimmune disorders: a comprehensive review of available epidemiological evidence with insights on potential underlying mechanisms

Several lines of evidence support a role of the immune system in headache pathogenesis, with particular regard to migraine. Firstly, alterations in cytokine profile and in lymphocyte subsets have been reported in headache patients. Secondly, several genetic and environmental pathogenic factors seem to be frequently shared by headache and immunological/autoimmune diseases. Accordingly, immunological alterations in primary headaches, in particular in migraine, have been suggested to predispose some patients to the development of immunological and autoimmune diseases. On the other hand, pathogenic mechanisms underlying autoimmune disorders, in some cases, seem to favour the onset of headache. Therefore, an association between headache and immunological/autoimmune disorders has been thoroughly investigated in the last years. The knowledge of this possible association may have relevant implications in the clinical practice when deciding diagnostic and therapeutic approaches. The present review summarizes findings to date regarding the plausible relationship between headache and immunological/autoimmune disorders, starting from a description of immunological alteration of primary headaches, and moving onward to the evidence supporting a potential link between headache and each specific autoimmune/immunological disease.

Immunological investigations of the cerebrospinal fluid in patients with recent onset psychotic disorders: A study protocol

Background Though many previous studies have indicated immunological alterations in psychotic disorders, the role and prevalence of neuroinflammation is still unknown. Studies previously investigating immune related biomarkers in the cerebrospinal fluid (CSF) of these patients are mainly small studies on few markers, and many have not compared patients to healthy controls. Methods We will conduct a large case-control study including at least 100 patients with recent onset psychotic disorders and 100 sex- and age matched healthy controls. The cases will include patients diagnosed with a psychotic disorder according to ICD-10 (F20/F22-29) within a year prior to inclusion. We will collect both CSF, blood and fecal samples, to gain insight into possible immunological alterations. The psychopathology of all participants will thoroughly be evaluated using the SCAN interview, and multiple rating scales covering different symptom groups. All participants will partake in a detailed neurological examination, including the Neurological Evaluation Scale assessing neurological soft signs. Additionally, we will assess cognitive functioning, evaluate quality of life and level of functioning, and collect data on a broad array of possible confounders. Our primary outcomes will include CSF leucocytes, CSF/serum albumin ratio, CSF total protein, IgG index, CSF levels of IL-6 and IL-8, and presence of antineuronal autoantibodies in CSF and blood. For our secondary outcomes, exploratory analyses will be performed on a broader panel of neuroimmunological markers. All participants will be invited for a follow-up visit to assess longitudinal changes. The current study is part of a larger CSF biobank build-up for severe mental disorders (PSYCH-FLAME). Discussion This study will represent the largest investigation of CSF in patients with psychotic disorders compared to healthy controls to date. We expect the study to contribute with new, important knowledge on pathophysiological mechanisms, and to help pave the way for future investigations of individualized treatment options. Trial registration The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2pos subjects

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.

Contribution of Gut Microbiota to Immunological Changes in Alzheimer’s Disease

Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer’s disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature on microbiota composition in AD patients and relevant animal models. Next, we highlight how microbiota and their metabolites may contribute to peripheral and central immunological changes in AD. Finally, we offer a future perspective on the translation of these findings into clinical practice by targeting gut microbiota to modulate inflammation in AD. Since we find that gut microbiota alterations in AD can induce peripheral and central immunological changes via the release of microbial metabolites, we propose that modulating their composition may alter ongoing inflammation and could therefore be a promising future strategy to fight progression of AD.