Autoreactive B cells remain active despite clinical disease control in rheumatoid arthritis.

BACKGROUND: Autoimmune diseases (AIDs) are frequently hallmarked by the presence of autoreactive B cell responses which are involved in disease pathogenesis. However, the dynamics of such responses and their relation to clinical disease activity in humans is poorly understood. Rheumatoid arthritis (RA), a prototypic chronic AID, is hallmarked by B cell responses directed against citrullinated proteins. OBJECTIVE: To determine the relation between the activity of the anti-citrullinated protein antibody (ACPA) B cell response and clinical disease activity in ACPA+ patients with RA. METHODS: Expression of B cell activation markers by ACPA+, tetanus toxoid (TT)+ and ACPA- memory B cells (MBCs) from peripheral blood of ACPA+ RA patients receiving different treatments was analyzed by flow cytometry. Results were correlated to clinical disease activity. RESULTS: Compared to TT+ and ACPA- MBCs, ACPA+ MBCs displayed a highly activated phenotype as evidenced by increased expression of Ki-67, CD86, CD80, CD19 and CD20 and reduced expression of CD32. The activated phenotype of ACPA+ MBCs did not associate with clinical disease activity in a cross-sectional analysis of RA patients treated with various therapeutic agents. Also, in a longitudinal analysis of patients treated with Janus kinase (JAK) inhibitors, ACPA+ MBCs retained their activated phenotype despite effective control of inflammation and clinical disease. CONCLUSION: ACPA+ MBCs remain active despite clinical disease control in patients with RA across a range of interventions. This persistent activity indicates the absence of immunological remission and might explain why ACPA+ patients rarely reach sustained drug-free remission and frequently flare upon drug tapering.

The relationship between the use of electronic nicotine delivery systems (ENDS) and effects on pulmonary immune responses-a literature review.

INTRODUCTION: The use of electronic nicotine delivery systems (ENDS), or vaping, is a relatively recent phenomenon, and there are various gaps in our current knowledge regarding the specific effects of e-cigarettes, such as their immunological effects. The importance of this question became even more relevant in light of the COVID-19 pandemic. OBJECTIVE: This literature review examines the relationship between the use of electronic nicotine delivery systems (ENDS) and immunological effects to examine available information and identify gaps in the current knowledge. Our search strategy included studies focusing on the effects of ENDS on the immune response during infectious respiratory diseases such as COVID-19 and pneumonia. METHODS: Peer-reviewed studies presenting quantitative data published from 2007, the year that e-cigarettes were introduced to the US market until 2022 have been included. All studies were indexed in PubMed. We excluded papers on THC and EVALI (E-cigarette, or Vaping Product, Use Associated Lung Injury) as we wanted to focus on the effects of nicotine devices. RESULTS: Among the 21 articles that assessed the relationship between ENDS and immunological health effects, we found eight studies based on cell models, two articles based on both cell and mouse models, five articles based on mouse models, and six studies of human populations. Most of the articles identified in our review demonstrated a potential association between vaping and adverse immunological health effects. DISCUSSION: Overall, the evidence from the cell and animal studies indicates that there is a positive, statistically significant association between vaping and adverse immune response during infectious respiratory diseases. The evidence from human studies is not conclusive.

Adipose Tissue-Derived Stem Cells: Immunomodulatory Effects and Therapeutic Potential.

Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability to regulate the immune system by secreting anti-inflammatory cytokines and growth factors that play a crucial role in the pathology of many diseases, including multiple sclerosis, diabetes mellitus, Crohn's, SLE, and graft-versus-host disease. The immunomodulatory effects and mechanisms of action of ASCs on pathological conditions are reviewed here.

Secondary myopathy due to systemic diseases.

BACKGROUND: Some systemic diseases also affect the skeletal muscle to various degrees and with different manifestations. This review aimed at summarizing and discussing recent advances concerning the management of muscle disease in systemic diseases. METHOD: Literature review by search of MEDLINE, and Current Contents with appropriate search terms. RESULTS: Secondary muscle disease occurs in infectious disease, endocrine disorders, metabolic disorders, immunological disease, vascular diseases, hematological disorders, and malignancies. Muscle manifestations in these categories include pathogen-caused myositis, muscle infarction, rhabdomyolysis, myasthenia, immune-mediated myositis, necrotising myopathy, or vasculitis-associated myopathy. Muscle affection may concern only a single muscle, a group of muscles, or the entire musculature. Severity of muscle affection may be transient or permanent, may be a minor part of or may dominate the clinical picture, or may be mild or severe, requiring invasive measures including artificial ventilation if the respiratory muscles are additionally involved. Diagnostic work-up is similar to that of primary myopathies by application of non-invasive and invasive techniques. Treatment of muscle involvement in systemic diseases is based on elimination of the underlying cause and supportive measures. The prognosis is usually fair if the causative disorder is effectively treatable but can be fatal in single cases if the entire musculature including the respiratory muscles is involved, in case of infection, or in case of severe rhabdomyolysis. CONCLUSION: Secondary muscle manifestations of systemic diseases must be addressed and appropriately managed. Prognosis of secondary muscle disease in systemic diseases is usually fair if the underlying condition is accessible to treatment.

Perspectives and challenges in developing small molecules targeting purine nucleoside phosphorylase.

As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions but also in immune system, including cell growth, apoptosis and cancer development and progression. Based on its T-cell targeting profile, PNP is a potential target for the treatment of some malignant T-cell proliferative cancers including lymphoma and leukemia, and some specific immunological diseases. Numerous small-molecule PNP inhibitors have been developed so far. However, only Peldesine, Forodesine and Ulodesine have entered clinical trials and exhibited some potential for the treatment of T-cell leukemia and gout. The most recent direction in PNP inhibitor development has been focused on PNP small-molecule inhibitors with better potency, selectivity, and pharmacokinetic property. In this perspective, considering the structure, biological functions, and disease relevance of PNP, we highlight the recent research progress in PNP small-molecule inhibitor development and discuss prospective strategies for designing additional PNP therapeutic agents.

Influence of HIV/AIDS Infection on Immunological and Nutritional Status in Adults and Older Adults: A Cross-Sectional Study in Kingdom of Bahrain.

Background and Objectives: HIV infection is a global public health problem that can lead to the progression of AIDS. Nutritional status and biochemical markers can significantly contribute to the progression of AIDS in HIV/AIDS patients. The main objective of this study is to examine the association between nutritional and biochemical markers as well as BMI in HIV/AIDS patients in the kingdom of Bahrain. Methods: A retrospective cohort study, including 300 patients (248 males and 52 females) with HIV/AIDS in Bahrain, was carried out. Various biochemical markers were collected from patients' medical records, including CD4+ T cell count, albumin, Hb, HCT, MCV, WBCs, and creatinine. A semi-structured questionnaire using a standardized food frequency questionnaire (FFQ) was used, from which total energy and total macronutrients were calculated. Results: The mean BMI of the participants was 27.20 kg/m2, and none of the participants had a BMI lower than 18.5 kg/m2 (underweight). The majority of patients' dietary intake of macronutrients and total calorie intake were either within or above the recommended RDA levels. The results also showed that all of the mean values of the nutritional and biochemical markers (CD4+ T cell count, albumin, Hb, HCT, MCV, WBCs, and creatinine) were within the normal reference ranges. A significant positive correlation between CD4+ T cell count, Hb, HCT, and albumin at the <0.05 level was found. There was no significant correlation between CD4+ T cell count and MCV, WBCs, and creatinine. A positive significant correlation was found between BMI, CD4+ T cell count, and WBCs at the <0.01 level. Conclusion: The BMI values were significantly correlated with the biochemical markers of AIDS progression. The dietary patterns of the participants were undiversified, with a high prevalence of obesity and overweight. Malnutrition among this study population was not present.

Is Curcumin a Safe and Effective Therapeutic in the Treatment against Oral Lichen Planus?

Oral lichen planus (OLP) is a chronic mucocutaneous, immunological disease that occurs more frequently in the buccal mucosa of middle-aged female patients. OLP's standard treatment is topical or systemic corticosteroids. Due to corticosteroids' numerous potential side effects, there is an effort to find an alternative treatment. One alternative treatment is curcumin. Several studies have investigated the effectiveness and safety of curcumin in OLP patients. In this review, we summarized the literature focusing on the effectiveness and safety of curcumin in OLP patients. Our review of clinical trials revealed that either 6000 mg/day curcumin, 80 mg/day nano-curcumin, or 1% curcumin oral gel 6 times/day offered benefits in the treatment of OLP.

The preventive Effectiveness of Rituximab in Pediatric Autoimmune and Inflammatory CNS Diseases Relapse: an Iranian Experience.

Objectives: To determine the effectiveness of Rituximab (RTX) therapy as the first therapeutic choice for the long-term prevention of secondary relapse in children with AIND that had relapse after primary treatment with immunosuppressive agents other than RTX. Materials & Methods: We conducted a single-center retrospective study of 9 consecutive pediatric patients (≤ 18 years old) registered on Autoimmune and Demyelinating Disorders Database (ADDD) of Mofid Children Hospital, from 2012 to 2016 and experienced relapse following therapeutic interventions with immunosuppressive agents other than RTX. Result: A remarkable reduction of 94.13% (p=0.015) occurred in annualized relapse rate (ARR) as a clinical indicator of therapeutic efficacy comparing before and after initiating RTX therapy. Conclusion: Rituximab is an effective drug in relapse prevention of AIND when administrated to patients for whom initial treatment with other immunosuppressive agents fail.POWER OF EVIDENCE: This study represents Class IV evidence that RTX therapy significantly reduces ARR in pediatric AIND including DDCNS.

Human Immune System Diseasome Networks and Female Oviductal Microenvironment: New Horizons to be Discovered.

Human hypofertility and infertility are two worldwide conditions experiencing nowadays an alarming increase due to a complex ensemble of events. The immune system has been suggested as one of the responsible for some of the etiopathogenic mechanisms involved in these conditions. To shed some light into the strong correlation between the reproductive and immune system, as can be inferred by the several and valuable manuscripts published to date, here we built a network using a useful bioinformatic tool (DisGeNET), in which the key genes involved in the sperm-oviduct interaction were linked. This constitutes an important event related with Human fertility since this interaction, and specially the spermatozoa, represents a not-self entity immunotolerated by the female. As a result, we discovered that some proteins involved in the sperm-oviduct interaction are implicated in several immune system diseases while, at the same time, some immune system diseases could interfere by using different pathways with the reproduction process. The data presented here could be of great importance to understand the involvement of the immune system in fertility reduction in Humans, setting the basis for potential immune therapeutic tools in the near future.

Interleukin-19 as an Immunoregulatory Cytokine.

IL-19 is a type of anti-inflammatory cytokine. Since the receptor for IL-19 is common to IL-20 and IL-24, it is important to clarify the role of each of the three cytokines. If three different cytokines bind to the same receptor, these three may have been produced to complement the other two. However, perhaps it is unlikely. Recently, the existence of a novel receptor for IL-19 was suggested. The distinction between the roles of the three cytokines still makes sense. On the other hand, because T cells do not produce IL-19, their role in acquired immunity is limited or indirect. It has been reported that IL-19 causes inflammation in some diseases but does not have an anti-inflammatory effect. In this review, we introduce the current role of IL-19 in each disease. In addition, we will describe the molecular mechanism of IL-19 and its development for the prevention of diseases. IL-19 was previously considered an anti-inflammatory cytokine, but we would like to propose it as an immunoregulatory cytokine.