Potential Therapeutic Application of Regulatory T Cells in Diabetes Mellitus Type 1

The autoimmune reaction against the beta cells of the pancreatic islets in type 1 diabetes mellitus (T1DM) patients is active in prediabetes and during the development of the clinical manifestation of T1DM, but it decreases within a few years of the clinical manifestation of this disease. A key role in the pathogenesis of T1DM is played by regulatory T cell (Treg) deficiency or dysfunction. Immune interventions, such as potential therapeutic applications or the induction of the Treg-cell population in T1DM, will be important in the development of new types of treatment. The aim of this study was to evaluate innovative immune interventions as treatments for T1DM. After an evaluation of full-length papers from the PubMed database from 2010 to 2021, 20 trials were included for the final analysis. The analysis led to the following conclusions: Treg cells play an important role in the limitation of the development of T1DM, the activation or application of Tregs may be more effective in the early stages of T1DM development, and the therapeutic use of Treg cells in T1DM is promising but requires long-term observation in a large group of patients.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome of femoral neoplasm-like onset: a case-based review

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an umbrella term covering a constellation of bone lesions and skin manifestations, but has rarely been clarified in the clinic. We report a 28-year-old woman who had initial onset of SAPHO syndrome with involvement of the femur, and she experienced a tortuous diagnostic course. We also performed a literature review of SAPHO syndrome cases involving the femur and summarize several empirical conclusions by integrating previous findings with our case. Furthermore, we propose our perspective that ailment of the skin caused by infection of pathogens might be the first hit for triggering or perpetuating the activation of the immune system. As a result, musculoskeletal manifestations are probably the second hit by crosstalk of an autoimmune reaction. The skin manifestations preceding bone lesions can be well explained. Current interventions for SAPHO syndrome remain controversial, but drugs aiming at symptom relief could serve as the first preference for treatment. An accurate diagnosis and appropriate treatment can cure patients in a timely manner. Although the pathogenesis of SAPHO syndrome remains to be determined, physicians and surgeons still need to heighten awareness of this entity to avoid invasive procedures, such as frequent biopsies or nonessential ostectomy.

Case Report on Encephalitis

Background: Encephalitis is type of brain inflammation caused by a virus, although it can also be caused by a bacterial or fungal infection or an autoimmune reaction. Encephalitis is a viral or inflammatory brain infection causes fever and headache as well as a low level of awareness, altered mental status (confusion, behavior abnormalities) localized neurologic impairments, and new onset seizure activity. Case Presentation: The case 7 year, old female patient who was alright one month back admitted in “A.V.B.R. Hospital, Wardha, on date 01/12/2020 with the chief complaint of high grade fever, headache, vomiting, irritability, and alteration of speech and generalized weakness. The patient had undergone various investigation complete blood count, urine analysis, kidney function test, liver function test, peripheral smear and virology test. Cerebrospinal fluid, electroencephalogram (EEG) Test, Magnetic resonance imaging (MRI) test, in MRI report shows altered gyral signal intensity is right fronto-parietal lobe with edema with thickened overlying cortex with effacement of adjacent sulcal spaces features suggestive of viral encephalitis. The patient was treated with antipyretic, antibiotic, loop diuretic, steroid, antiemetic drug to treat vomiting. Monitor all vital signs, checked and recorded intake and output, administered medication as prescribed by doctors. Conclusion: The inflammation of the brain causes encephalitis, which is a rare but deadly disorder. It can be life -threatening and necessitates immediate hospitalization. Anyone can be harmed, but the very young and elderly are the most vulnerable.

Efficacy of rituximab in autism spectrum disorders associated with hereditary folate malabsorption with signs of antineuronal autoimmunity

Background. One of the key advances in psychiatry is an elucidation of the association of hereditary folate malabsorption (HFM) with autistic spectrum disorders (ASD), the evidence for which is based on the results of 5 meta-analyses of randomized controlled trials. It is shown that in such cases the antineuronal autoimmune reaction is an important mechanism of encephalopathy formation. The purpose of the study was to investigate the efficacy of rituximab in children with HFM-associated ASD who showed serological signs of antineuronal autoimmunity to expand the current arsenal of neuroprotective therapy in immunodependent encephalopathy in such cases. Materials and methods. Medical data of 138 children aged 3 to 8 years with HFM and ASD (97 boys and 41 girls) were analyzed. Parents of 62 of 81 patients with signs of antineuronal autoimmunity agreed to rituximab immunotherapy at a dose of 375 mg/m2 of body surface area per month for 3–9 months (study group, SG). Relatives of the other 19 patients with a similar distribution of antineuronal autoantibodies refused treatment (control group, CG). The dynamics of the mental state of children during immunotherapy was assessed by the ABC scale. For statistical analysis, we calculated the parametric Student’s t-test with the confidence probability p and the non-parametric criterion — the number of signs Z by U.V. Urbach, as well as the odds ratio (OR) and 95% confidence interval (95% CI). Results. Rituximab treatment resulted in a progressive decrease in serum antineuronal autoantibodies concentration in patients with ASD associated with HFM, with a more pronounced effect in the production of autoantibodies to neuronal potassium channels compared to autoantibodies to the GADA with complete elimination of the seropositivity after a 9-month course of immunotherapy in 92 % of cases. The phenomenon of rituximab-induced elimination of serum antineuronal autoantibodies is associated with the effect of neuroprotection, which was confirmed by the normalization of previously elevated serum concentrations of laboratory biomarkers of NSE cerebral damage (OR = 17.875; 95% CI = 4.738–67.436 at Ab to GADA and 41.800; 7.257–240.778 at Ab to potassium channels) and S-100 protein (9.750; 2.707–35.113 and 18.333; 3.462–97.083, respectively). In parallel, there was a progressive improvement in all indicators of the mental status of children with ASD on the ABC scale with a latency period of about 2 months (p < 0.05: Z < Z0.05). Conclusions. Immunotherapy with rituximab by eliminating the serological signs of antineuronal autoimmunity realizes the effect of neuroprotection, reducing the severity of all major clinical signs of ASD in children with HFM.

Quantum, Brain, and Immunity Triangle in Mental Health and Neurosciences

Immunopsychiatry is a fledgling research field with great potential in the etiological research of psychotic disorders and can turn out to be helpful in finding novel treatment strategies and repurposing existing therapeutic agents. The clinical applications of Neuroquantology complement some of the etiological views of psychotic disorders that are evolving in immunopsychiatry. The pathogenesis of psychotic process may involve an underlying immune disturbance leading to neuro-quantological disorders. The cytokine storm that occurs due to COVID-19 and the resulting neurotoxic effects illustrate how an autoimmune reaction can potentially form psychotic symptoms through the mediation of the brain. Studying the interconnection between neurotransmission and immunity has significant relevance in the etiopathogenesis of psychiatric disorders. Immunopsychiatry alone may not be adequate to explain the development of psychotic symptoms, but Neuroquantology and immunopsychiatry complement each other in this endeavor. An expanded model of the brain–mind consciousness complex is required to understand the intricacies of psychotic symptomatology and contributions from Neuroquantology are highly enrichening. The claims of the practitioners of quantum immunotherapies need further exploration. Quantum-brain and immunity triangle can result in a huge paradigmatic shift in our understanding of psychiatric disorders and the evolving landscape of immunopsychiatry and clinical Neuroquantology warrant further promotion.

Polymorphic variants of proteasomal genes PSMA3 and PSMA6 in children with articular syndrome and juvenile idiopathic arthritis

A comparative analysis of three single nucleotide variations of the proteasomal genes PSMA3 (rs2348071) and PSMA6 (rs2277460 and rs1048990) was carried out in the groups of children from 1 to 16 years old with the autoimmune rheumatic disease - juvenile idiopathic arthritis (JIA; n = 199), with articular syndrome of non-autoimmune etiology (n = 229) and in the clinical control group with neither autoimmune nor chronic inflammatory diseases (n = 379). PCR, PCR–RFLP and real-time PCR were used for genotyping. It was found that the CG genotype and G allele of rs10489990 polymorphism (OR = = 1.93; 95 % CI 1.29-2.90; p = 0.002 and OR = 1.51; 95 % CI 1.11-2.04; p = 0.008 respectively), as well as the AA genotype of rs2348071 polymorphism (OR = 1.89; 95 % CI 1.02–3.49; p = 0.044) are associated with the JIA susceptibility, but not with articular syndrome. The established JIA risk genotypes may indicate the involvement of PSMA3 and PSMA6 genes in the development of an autoimmune reaction. In combination with other risk DNA markers, they can be proposed to assess a genetic predisposition to JIA. It was also revealed that the frequencies of risk genotypes and alleles for JIA in the group of patients with articular syndrome as a whole occupy an intermediate position between JIA and control group frequencies. This may indicate an increased JIA risk in some patients with articular syndrome.

Acute Lymphoblastic Leukemia Complicating Graves’ Disease in a Sudanese Adolescent Girl: A Case Report and Exploration of the Underlying Mechanism Possibilities

Background: Graves’ Disease (GD) related bone marrow injury presents usually as agranulocytosis or less commonly as pancytopenia. However, acute lymphoblastic leukemia (ALL) has been reported recently in an adult patient with GD. The underlying pathogenesis is not fully understood. Nevertheless, the harmful effect of anti-thyroid drugs or autoimmune reaction to bone marrow cells is anticipated to be the causative factors. Case report: A 16.5-year-old Sudanese girl with GD was on carbimazole for the first fourteen months of her illness, with irregular follow up, then it was withdrawn because she developed hypothyroidism for which she was put on thyroxine. Meanwhile, she developed severe anemia without fever which necessitated blood transfusion. Eight months later, she presented with thyrotoxicosis relapse, febrile illness and pancytopenia which was proved to be ALL on bone marrow examination. Conclusion: ALL must be considered when encountering a GD patient with pancytopenia.

Cytokine Storms in the Course of COVID-19 and Haemophagocytic Lymphohistiocytosis in Pregnant and Postpartum Women

The term ‘cytokine storm’ (CS) applies to a pathological autoimmune reaction when the interactions that lead to cytokine production are destabilised and may even lead to death. CS may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we present our analysis of certain pathological processes that induce a CS in pregnant and postpartum women. We draw our attention to the similarities between the severe course of Coronavirus Disease 2019 (COVID-19) and haemophagocytic lymphohistiocytosis (HLH). It is noteworthy that many of the criteria used to diagnose HLH are described as COVID-19 mortality predictors. Cytokine storms are considered to be an important cause of death in patients with the severe course of SARS-CoV-2 infection. Due to the fact that pregnant women are in an immunosuppressive state, viral pulmonary infections are more perilous for them—possible risks include miscarriage, intrauterine growth restriction or birth before the term; sometimes ventilation support is needed. HLH should be considered in pregnant and puerperal women suffering from moderately severe to severe COVID-19 and presenting with: fever unresponsive to antibiotic therapy, cytopenia, hepatitis and hyperferritinaemia. The HLH disorder is rare and difficult to diagnose; however, its early detection could reduce patient mortality.

Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were generated, and induced lupus-like symptoms. Eight months later, the TG mice spontaneously developed typical SLE symptoms regardless of the inducement. Furthermore, we observed increased toll-like receptor 7 (TLR7) expression with increased monocyte and neutrophil populations in the TG mice. In conclusion, overexpression of CTSS in mice influences TLR7 expression, autoantibodies and IFN-α, which leads to an autoimmune reaction and exacerbates lupus-like symptoms.