Fecal microbiota transplantation in autoimmune diseases - An extensive paper on a pathogenetic therapy.

The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed.

Antiphospholipid syndrome in the era of COVID-19 - Two sides of a coin.

In addition to the respiratory symptoms associated with COVID-19, the disease has consistently been linked to many autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome (APS). APS in particular was of paramount significance due to its devastating clinical sequela. In fact, the hypercoagulable state seen in patients with acute COVID-19 and the critical role of anticoagulant treatment in affected individuals shed light on the possible relatedness between APS and COVID-19. Moreover, the role of autoimmunity in the assumed association is not less important especially with the accumulated data available regarding the autoimmunity-triggering effect of SARS-CoV-2 infection. This is furtherly strengthened at the time patients with COVID-19 manifested antiphospholipid antibodies of different types following infection. Additionally, the severe form of the APS spectrum, catastrophic APS (CAPS), was shown to have overlapping characteristics with severe COVID-19 such as cytokine storm and multi-organ failure. Interestingly, COVID vaccine-induced autoimmune phenomena described in the medical literature have pointed to an association with APS. Whether the antiphospholipid antibodies were present or de novo, COVID vaccine-induced vascular thrombosis in certain individuals necessitates further investigations regarding the possible mechanisms involved. In our current paper, we aimed to focus on the associations mentioned, their implications, importance, and consequences.

The existence of a bidirectional link between ischemic heart disease and fibromyalgia.

STUDY OBJECTIVES: Fibromyalgia (FM) is one of the most common causes of chronic widespread musculoskeletal pain, but also sleep disturbances, cognitive and psychological disorders. It has been suggested that FM may have a correlation with cardiovascular events. In this study, we aimed to assess the association between FM and ischemic heart disease (IHD). METHODS: A population-based cross-sectional study was conducted utilizing data retrieved from the largest medical records database in Israel, Clalit Health Services. Patients were defined as having FM or IHD when there were at least two such documented diagnoses in their medical records. The occurrence of IHD was compared between FM and age- and sex-frequency-matched healthy controls. A logistic regression model was used to estimate this association following an adjustment for conventional cardiovascular risk factors and depression. RESULTS: An overall population of 18 598 FM patients and 36 985 age- and gender-matched controls were included in the study. The proportion of IHD amongst FM patients was increased in comparison to controls (9.2% and 6.2%, respectively; P  < 0.001). Furthermore, FM demonstrated an independent association with IHD on multivariate analysis (odds ratio [OR], 1.43; 95% confidence intervals [CI], 1.33-1.54; P  < 0.0001). Finally, IHD was also found to be independently associated with the diagnosis of FM (OR, 1.40; CI, 1.31-1.51; P  < 0.0001). CONCLUSION: Our data suggest a bidirectional link between FM and IHD even after the adjustment for conventional cardiovascular risk factors. These findings should be considered when treating patients with either FM or IHD, and their routine interactional screening may be of clinical importance.

COVID-19 and SLE: Infection and autoimmunity at its best.

If one had any doubts before the pandemic regarding the correlation between infections and autoimmunity, COVID-19 left us fascinated on the strong bond between the two entities. The immune and autoimmune reactions seen in patients infected with SARS-CoV-2 have served as a base for this assumption. Later on, the use of immunosuppressants such as systemic glucocorticoids, among other biological agents, turned this assumption to a fact. This was no different when it comes to the vaccines against COVID-19. Through several postulated mechanisms these vaccines, although generally considered safe, are thought to have the potential to result in autoimmune reactions making them not more innocent than the infection itself. When systemic lupus erythematous (SLE) is viewed as a classical autoimmune multisystemic disorder, the connection with SARS-CoV-2 infection and COVID-19 vaccination is of extreme importance. This is because early reports during the pandemic have shown increased rates of SARS-CoV-2 infection among patients known previously to have SLE and much more interestingly, cases of new-onset SLE after COVID-19 have been documented in the literature. Subsequently vaccines against COVID-19, those mRNA-based and adenovirus-vector based, were reported to induce new SLE cases, trigger immune thrombocytopenia or lupus nephritis, two common presentations of SLE, or exacerbate flares. In our paper, we concluded various aspects of available and recent data regarding SLE and COVID-19 as both an infection and vaccination.

Triggers and regulation: the gut microbiome in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis is a chronic inflammatory disease marked by systemic symptoms and joint degeneration. Interestingly, the development and progression of rheumatoid arthritis have been linked to the microbiome, notably the gut microbiome. Dysbiosis, an alteration in the gut microbiome, has been connected to the etiology and pathogenesis of rheumatoid arthritis. For instance, dysbiosis increases intestinal permeability and promotes the movement of bacteria and their products, which in turn triggers and aggravates systemic inflammation. AREAS COVERED: The correlation between the gut microbiome and RA. Triggers of RA including dysbiosis. The therapeutic potential of the gut microbiome in RA due to its critical function in influencing the immune response. The fecal microbiota transplantation (FMT), a therapeutic strategy that involves the transfer of healthy fecal microbiota from a donor to a recipient, has produced encouraging results in the treatment of several autoimmune illnesses, including rheumatoid arthritis. EXPERT OPINION: The role of the gut microbiome in RA is critical and serves as a basis for etiology and pathogenesis, as well as having therapeutic implications. In our opinion, FMT is an excellent example of this correlation. Still, more investigations and well-designed studies are needed in order to make firm conclusions and recommendations.

Shared Pathogenicity Features and Sequences between EBV, SARS-CoV-2, and HLA Class I Molecule-binding Motifs with a Potential Role in Autoimmunity.

Epstein-Barr virus (EBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are extraordinary in their ability to activate autoimmunity as well as to induce diverse autoimmune diseases. Here we reviewed the current knowledge on their relation. Further, we suggested that molecular mimicry could be a possible common mechanism of autoimmunity induction in the susceptible individuals infected with SARS-CoV-2. Molecular mimicry between SARS-CoV-2 and human proteins, and EBV and human proteins, are present. Besides, relation of the pathogenicity associated with both coronavirus diseases and EBV supports the notion. As a proof-of-the-concept, we investigated 8mer sequences with shared 5mers of SARS-CoV-2, EBV, and human proteins, which were predicted as epitopes binding to the same human leukocyte antigen (HLA) supertype representatives. We identified significant number of human peptide sequences with predicted-affinities to the HLA-A*02:01 allele. Rest of the peptide sequences had predicted-affinities to the HLA-A*02:01, HLA-B*40:01, HLA-B*27:05, HLA-A*01:01, and HLA-B*39:01 alleles. Carriers of these serotypes can be under a higher risk of autoimmune response induction upon getting infected, through molecular mimicry-based mechanisms common to SARS-CoV-2 and EBV infections. We additionally reviewed established associations of the identified proteins with the EBV-related pathogenicity and with the autoimmune diseases.

ChatGPT and autoimmunity - A new weapon in the battlefield of knowledge.

The field of medical research has been always full of innovation and huge leaps revolutionizing the scientific world. In the recent years, we have witnessed this firsthand by the evolution of Artificial Intelligence (AI), with ChatGPT being the most recent example. ChatGPT is a language chat bot which generates human-like texts based on data from the internet. If viewed from a medical point view, ChatGPT has shown capabilities of composing medical texts similar to those depicted by experienced authors, to solve clinical cases, to provide medical solutions, among other fascinating performances. Nevertheless, the value of the results, limitations, and clinical implications still need to be carefully evaluated. In our current paper on the role of ChatGPT in clinical medicine, particularly in the field of autoimmunity, we aimed to illustrate the implication of this technology alongside the latest utilization and limitations. In addition, we included an expert opinion on the cyber-related aspects of the bot potentially contributing to the risks attributed to its use, alongside proposed defense mechanisms. All of that, while taking into consideration the rapidity of the continuous improvement AI experiences on a daily basis.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA): past, present, and future implications.

Adjuvants, as the name indicates, are adjoined material aimed to assist in functioning as when added to vaccines they are meant to boost the effect and strongly stimulate the immune system. The response of the immune system can be unpredictable, and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was developed to address possible adverse reactions of an autoimmune and inflammatory type that may be caused by adjuvants. While ASIA, as a syndrome, was coined and defined in 2011; reports describing patients with vague and nonspecific clinical symptoms following vaccinations appeared much earlier. In other words, ASIA came to define, arrange, and unite the variety of symptoms, related to autoimmunity, caused not by the vaccine itself, rather by the adjuvant part of the vaccine such as aluminum, among others. Accordingly, the introduction of ASIA enabled better understanding, proper diagnosis, and early treatment of the disorder. Furthermore, ASIA was shown to be associated with almost all body systems and various rheumatic and autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and systemic sclerosis. In addition, the correlation between COVID-19 and ASIA was noticed during the pandemic. In this review, we summarized the reported effects of adjuvants and medical literature before and after ASIA was defined, the several ways ASIA can manifest and impact different systems of the body, and the incidences of ASIA during the COVID-19 pandemic. It is important to clarify, that vaccines are among, if not the, most effective means of fighting infectious diseases however, we believe that vaccines manufacturing is not above criticism, particularly when it comes to added substances possessing a risk of side effects.

Vaccines and Autoimmunity-From Side Effects to ASIA Syndrome.

Since vaccines are in fact manufactured chemical compounds such as drugs, the appearance of side effects following their use is not surprising. Similarly, as the main goal of vaccines is to stimulate the immune system bringing out the production of protective antibodies, autoimmune-related side effects as a consequence of increased immune activity do not seem irrational. Fortunately, the rate of such side effects is low; however, the importance of reporting adverse events following vaccinations, understanding the mechanisms behind their appearance, making early diagnosis, and appropriate treatment cannot be overemphasized. In fact, autoimmune-related side effects of vaccines, particularly those based on adjuvants, were reported long before the introduction of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Nevertheless, ASIA gathered and united the side effects of vaccines under one title, a step which helped organize the research and call for better immune stimulators than adjuvants. New technologies and methods of making vaccines were clearly noticed during the pandemic of COVID-19 after the introduction of mRNA-based vaccines. In our current paper, we introduce the notion of side effects to vaccines, particularly those of autoimmune nature, the mechanisms of ASIA, and the main vaccines linked with the syndrome including the recent COVID-19 vaccines. The transition from side effects to ASIA is the main idea behind our work.

Celebrities and Medical Awareness-The Case of Celine Dion and Stiff-Person Syndrome.

The positive role of celebrities in spreading important medical information and contributing to increasing public awareness regarding the diagnosis, treatment, and prevention of various medical conditions cannot be overemphasized. Interestingly and importantly at the same time, this impact is not related to the rarity of the disease, as very rare diseases are looked up by the public due to the fact that a celebrity suffers from this disorder. Therefore, if taken seriously and used to address the public in regard to critical medical conditions, such as screening for cancer or the importance of vaccines in fighting infections, celebrities could have a huge impact in this field. As previously shown in the medical literature, the recent announcement of the famous Canadian singer Celine Dion concerning her newly diagnosed stiff-person syndrome has influenced the public interest regarding the syndrome which manifested as an increased search volume related to the disorder as seen in Google Trends. In brief, in this short communication we aimed to address the phenomenon of celebrities' impact on public apprehension, revise the syndrome for the medical community, and emphasize taking advantage of such involvement of celebrities for improving the spread of highly important medical information for the public.

Epidemiological trends and clinical features of the ongoing monkeypox epidemic: A preliminary pooled data analysis and literature review.

An emerging outbreak of monkeypox infection is quickly spreading worldwide, being currently reported in more than 30 countries, with slightly less than 1000 cases. In the present preliminary report, we collected and synthesized early data concerning epidemiological trends and clinical features of the ongoing outbreak and we compared them with those of previous outbreaks. Data were pooled from six clusters in Italy, Australia, the Czech Republic, Portugal, and the United Kingdom, totaling 124 cases (for 35 of which it was possible to retrieve detailed information). The ongoing epidemic differs from previous outbreaks in terms of age (54.29% of individuals in their thirties), sex/gender (most cases being males), risk factors, and transmission route, with sexual transmission being highly likely. Also, the clinical presentation is atypical and unusual, being characterized by anogenital lesions and rashes that relatively spare the face and extremities. The most prevalent sign/symptom reported was fever (in 54.29% of cases) followed by inguinal lymphadenopathy (45.71%) and exanthema (40.00%). Asthenia, fatigue, and headache were described in 22.86% and 25.71% of the subjects, respectively. Myalgia was present in 17.14% of the cases. Both genital and anal lesions (ulcers and vesicles) were reported in 31.43% of the cases. Finally, cervical lymphadenopathy was described in 11.43% of the sample, while the least commonly reported symptoms were diarrhea and axillary lymphadenopathy (5.71% of the case series for both symptoms). Some preliminary risk factors can be identified (being a young male, having sex with other men, engaging in risky behaviors and activities, including condomless sex, human immunodeficiency virus positivity (54.29% of the sample analyzed), and a story of previous sexually transmitted infections, including syphilis). On the other hand, being fully virally suppressed and undetectable may protect against a more severe infectious course. However, further research in the field is urgently needed.

Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome.

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them. The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned. Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome, namely "autoimmune autonomic dysfunction syndromes". Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.

The mosaic of autoimmunity - Finally discussing in person. The 13th international congress on autoimmunity 2022 (AUTO13) Athens.

While autoimmunity is a branch of medicine linked to every single organ system via direct and indirect pathways, meeting in person to discuss autoimmunity during the 13th international congress on autoimmunity (AUTO13) with participants from all over the world had a very good reason. The mechanisms involved in autoimmune diseases are of extreme importance and in fact critical in understanding the course of diseases as well as selecting proper therapies. COVID-19 has served as a great example of how autoimmunity is deeply involved in the disease and directly correlated to severity, morbidity, and mortality. For instance, initially the term cytokine storm dominated, then COVID-19 was addressed as the new member of the hyperferritinemic syndrome, and also the use of immunosuppressants in patients with COVID-19 throughout the pandemic, all shed light on the fundamental role of autoimmunity. Unsurprisingly, SARS-CoV-2 was called the "autoimmune virus" during AUTO13. Subsequently, the correlation between autoimmunity and COVID-19 vaccines and post-COVID, all were discussed from different autoimmune aspects during the congress. In addition, updates on the mechanisms of diseases, autoantibodies, novel diagnostics and therapies in regard to autoimmune diseases such as antiphospholipid syndrome, systemic lupus erythematosus, systemic sclerosis and others, were discussed in dedicated sessions. Due to the magnificence of the topics discussed, we aimed to bring in our article hereby, the pearls of AUTO13 in terms of updates, new aspects of autoimmunity, and interesting findings. While more than 500 abstract were presented, concluding all the topics was not in reach, hence major findings were summarized.

HIV Pre-exposure Prophylaxis and Its Impact on the Gut Microbiome in Men Having Sex With Men.

HIV/AIDS still imposes a high epidemiological and societal burden. Together with antiretroviral therapy, pre-exposure prophylaxis (PrEP) represents a fundamental tool in the fight against HIV/AIDS. PrEP is considered effective and safe, even though it may affect organs like the kidney, bone, and liver, as shown by randomized clinical trials (RCTs). These side effects may be mediated by alterations of the gut microbiome. Whilst the impact of the human rectal and vaginal microbiome on HIV prevention has been highly investigated among women, less is known about its effect among men having sex with men (MSM), a vulnerable population at high risk for HIV and disproportionately affected by HIV/AIDS. In the present paper, we will overview the effects of PrEP on the gut microbiota in MSM. Mining PubMed/MEDLINE, we identified three studies that have found significant changes affecting the gut microbiota. However, these shifts in the gut microbiome composition are variable, probably due to methodological differences, even though all studies reviewed in the present overview consistently report aberrations at the level of the gut microbiota. More data are needed, especially concerning the long-term side effects of PrEP: despite the studies included being a high-quality RCT, and two well-designed cross-sectional studies, evidence related to the impact of HIV PrEP on the gut microbiome in MSM is scarce and based on small populations. A better understanding of the interactions between the gut microbiota, sexual orientation/identity, and HIV prevention is expected to improve PrEP adherence and devise strategies to counteract PrEP-related side effects.