Immune system disorders in the early post-injury period in patients after severe brain injury from the perspective of the severity of the injury.

BACKGROUND: Brain injuries are the most common cause of death in productive age. Besides the extent of the injury, other systemic factors can also affect the outcome. Patients suffering from severe brain injury often experience extracranial inflammatory complications during the early period of treatment. Here, we investigate the changes in immunity in patients with brain injury. METHODS: 121 patients and 92 healthy controls were included in the research. Blood samples were collected on admission and analyzed by flow cytometry and biochemical methods. Multiple clusters of differentiation (CD) and antibody levels were investigated. The results were compared between patients and controls. In addition, results of two classes of severity (Glasgow Coma Scale, GCS, of 3-5 vs. 6-8) were also compared. RESULTS: Parameters of humoral immunity in patients immediately after admission were significantly lower than those from healthy donors, with the exception of IgE elevated as much as to resemble allergic reaction (p < 0.01). Of cellular parameters, only natural killer (NK) cluster CD56 + was elevated (p < 0.01). Extracranial infectious complications were more common in patients with GCS 3-5. CONCLUSIONS: Strong immune system disorders were observed in patients after severe brain injury, which may contribute to the worse outcome in such patients.

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB, CD16B) deficiency in patients with blood and immune system disorders.

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB) deficiency is present in ˜0·05% of the general population. Among our patients, FcγRIIIB deficiency was less frequent in those with immune-system disorders (one of 1815 patients, 0·05%) than in those with blood disorders (nine of 2147 patients, 0·42%, P = 0·023): mainly primary immune thrombocytopenia (4·34%), therapy related myeloid neoplasms (1·16%) and myelodysplastic syndrome with excess blasts (1·28%). Four of the nine (44·4%) patients with blood disorders were diagnosed with or quickly evolved to acute myeloid leukaemia (AML), suggesting that FcγRIIIB deficiency could be an adverse prognostic factor for progression to AML that should be confirmed in large multicentre studies.

Impact of hydroxychloroquine on the gestational outcomes of pregnant women with immune system problems that necessitate the use of the drug.

AIM: To evaluate the impact of hydroxychloroquine (HCQ) on the perinatal outcomes of pregnancies with immune system disorders that necessitate the use of the drug. METHODS: This cohort consisted of 202 pregnancies with poor obstetric history and immune system problems. Patients enrolled in special antenatal care program were administered low-dose low-molecular-weight heparin, low-dose salicylic acid and low-dose corticosteroid (prophylaxis protocol) as soon as their pregnancies were confirmed. Pregnancies with systemic lupus erythematosis, Sjogren syndrome and rheumatoid arthritis were additionally administered HCQ 200 mg daily as a part of their routine treatment. Pregnancies using HCQ were included in the study group (n = 39) while the remainders were included in control group (n = 163). We compared the groups in terms of the presence of miscarriage, fetal growth restriction (FGR), preeclampsia and preterm birth, as well as gestational week at birth, birthweight and "APGAR score of <7" at 10th minute. RESULTS: Miscarriage rates were 28.2% and 28.2% while preterm birth rates were 16.6% and 28.2% in the control and study groups, respectively (P = 0.215). Preeclampsia and HCQ-related side effects were not detected in the groups. There were also no significant differences between the groups in terms of FGR, gestational day at birth, birthweight and the presence of "APGAR score <7" at 10th minute (P = 0.462, P = 0.064, P = 0.273 and P = 0.627, respectively). CONCLUSION: Low-dose low-molecular-weight heparin, low-dose salicylic acid and low-dose corticosteroid prophylaxis together with HCQ seem to be promising in pregnancies with immune system disorders. HCQ seems to be a safe and effective drug in low dosages.

Mold, Mycotoxins and a Dysregulated Immune System: A Combination of Concern?

Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding the role of mold and mycotoxins in the development of immune diseases. While the induction of allergic immune responses by molds is generally acknowledged, other direct health effects like the toxic mold syndrome are controversially discussed. However, recent observations indicate a particular importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system, due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and even human immunodeficiency virus (HIV) disease progression. In this review, we focus on the impact of mycotoxins regarding their impact on disease progression in pre-existing immune dysregulation. This is complemented by experimental in vivo and in vitro findings to present cellular and molecular modes of action. Furthermore, we discuss hypothetical mechanisms of action, where evidence is missing since much remains to be discovered.

[Alopecia areata universalis under treatment with sitagliptin : Possible immunological effect of dipeptidyl peptidase-4 inhibitors?] / Alopecia areata universalis nach Sitagliptin-Einnahme : Mögliche immunologische Wirkung von Dipeptidylpeptidase-4-Inhibitoren?

A 64-year old man developed alopecia universalis after one month of treatment with metformin and sitagliptin, a dipeptidyl peptidase­4 (DPP-4) inhibitor. Diabetes treatment was changed to another genericum of sitagliptin and dapagliflozin. Following our recommendation, sitagliptin was interrupted and monotherapy with dapagliflozin was continued. After 6 weeks, sitagliptin was reassumed due to unsatisfactory diabetes control. Alopecia did not improve. We suspect a connection between DPP­4 inhibition and development of alopecia due to its immunological potential. We assume that the treatment interruption might have been too short to induce regrowth of hair. DPP­4 may result in both inhibition and activation of the immune system.

[Immune system disorders in acute pyelonephritis. II art].

New information about typical changes in the immune status at both local and systemic level in various forms of acute pyelonephritis is provided in the second part of the review. The literature review and analysis of current national and foreign literature dedicated to immune disorders in various forms of acute pyelonephritis has been performed. The degree and nature of changes in systemic and local immunological parameters in nonobstructive and obstructive, serous and purulent forms are highlighted in details. In particular, it has been established that in patients with obstructive and purulent pyelonephritis, there are more pronounced changes in the serum and urine level of cytokines and complement factors in comparison with serous and non-obstructive pyelonephritis. Recommendations are given on monitoring of the immunological status in patients with various forms of acute pyelonephritis in order to optimize treatment approaches. In addition, the rationales for effective pathogenetic, including specific, immunotherapy drugs for various forms of pyelonephritis are presented.

Myelodysplastic syndrome with IgG4­related disease: A case report.

At present, to the best of our knowledge, there are only a few case reports of IgG4-related disease (IgG4-RD) involving myelodysplastic syndrome (MDS), yet the incidence of MDS and IgG4-RD is increasing in middle-aged and elderly people. The present study presents a case of MDS combined with IgG4-RD admitted to Zhejiang Provincial Hospital of Chinese Medicine in September 2022. The (66-year-old; male) patient was admitted to the hospital due to hematopenia with an elevated IgG4 index. The diagnosis of MDS combined with IgG4-RD was confirmed after various exams, including pathological examination. The condition of the patient improved after 3 weeks of hormone therapy, with a significant increase in complete blood count compared with the pre-treatment period. MDS is a malignant hematological disorder with a high risk of conversion to leukemia, and IgG4-RD is a systemic immune-mediated disease with a poor prognosis often associated with malignancy. The present study presents and reviews the literature to better understand the coexistence of these two diseases.

Study of the shared gene signatures of polyarticular juvenile idiopathic arthritis and autoimmune uveitis.

Objective: To explore the shared gene signatures and potential molecular mechanisms of polyarticular juvenile idiopathic arthritis (pJIA) and autoimmune uveitis (AU). Method: The microarray data of pJIA and AU from the Gene Expression Omnibus (GEO) database were downloaded and analyzed. The GEO2R tool was used to identify the shared differentially expressed genes (DEGs) and genes of extracellular proteins were identified among them. Then, weighted gene co-expression network analysis (WGCNA) was used to identify the shared immune-related genes (IRGs) related to pJIA and AU. Moreover, the shared transcription factors (TFs) and microRNAs (miRNAs) in pJIA and AU were acquired by comparing data from HumanTFDB, hTFtarget, GTRD, HMDD, and miRTarBase. Finally, Metascape and g: Profiler were used to carry out function enrichment analyses of previously identified gene sets. Results: We found 40 up-regulated and 15 down-regulated shared DEGs via GEO2R. Then 24 shared IRGs in positivity-related modules, and 18 shared IRGs in negatively-related modules were found after WGCNA. After that, 3 shared TFs (ARID1A, SMARCC2, SON) were screened. And the constructed TFs-shared DEGs network indicates a central role of ARID1A. Furthermore, hsa-miR-146 was found important in both diseases. The gene sets enrichment analyses suggested up-regulated shared DEGs, TFs targeted shared DEGs, and IRGs positivity-correlated with both diseases mainly enriched in neutrophil degranulation process, IL-4, IL-13, and cytokine signaling pathways. The IRGs negatively correlated with pJIA and AU mainly influence functions of the natural killer cell, cytotoxicity, and glomerular mesangial cell proliferation. The down-regulated shared DEGs and TFs targeted shared DEGs did not show particular functional enrichment. Conclusion: Our study fully demonstrated the flexibility and complexity of the immune system disorders involved in pJIA and AU. Neutrophil degranulation may be considered the shared pathogenic mechanism, and the roles of ARID1A and MiR-146a are worthy of further in-depth study. Other than that, the importance of periodic inspection of kidney function is also noteworthy.

Clinical utility of mesenchymal stem/stromal cells in regenerative medicine and cellular therapy.

Mesenchymal stem/stromal cells (MSCs) have been carefully examined to have tremendous potential in regenerative medicine. With their immunomodulatory and regenerative properties, MSCs have numerous applications within the clinical sector. MSCs have the properties of multilineage differentiation, paracrine signaling, and can be isolated from various tissues, which makes them a key candidate for applications in numerous organ systems. To accentuate the importance of MSC therapy for a range of clinical indications, this review highlights MSC-specific studies on the musculoskeletal, nervous, cardiovascular, and immune systems where most trials are reported. Furthermore, an updated list of the different types of MSCs used in clinical trials, as well as the key characteristics of each type of MSCs are included. Many of the studies mentioned revolve around the properties of MSC, such as exosome usage and MSC co-cultures with other cell types. It is worth noting that MSC clinical usage is not limited to these four systems, and MSCs continue to be tested to repair, regenerate, or modulate other diseased or injured organ systems. This review provides an updated compilation of MSCs in clinical trials that paves the way for improvement in the field of MSC therapy.

Eruptive pseudoangiomatosis in adults with immune system disorders: A report of two cases.

Eruptive pseudoangiomatosis is a cutaneous disease of unknown origin, characterized by the sudden appearance of small, asymptomatic angioma-like erythematous papules surrounded by a pale halo that resolves spontaneously. It occurs due to transitory dermal blood vessel dilation and has been associated with viral infections and hematologic disorders. To this day, it remains a disease that affects mostly the lower spectrum of life. Most of the cases have been reported in children and few reports have described its association with immune system disorders. The diagnosis is based upon clinical presentation. Histopathological analysis has no pathognomonic findings and can include dilated dermal blood vessels, perivascular lymphocytic infiltration and plump endothelial cells. We report a 21-years-old female diagnosed with HIV in AIDS stage and a 19- years-old male diagnosed with non- Hodgkin's lymphoma.

Titanium implants and silent inflammation in jawbone-a critical interplay of dissolved titanium particles and cytokines TNF-α and RANTES/CCL5 on overall health?

BACKGROUND AND INTRODUCTION: It is a well-known fact that titanium particles deriving from dental titanium implants (DTI) dissolve into the surrounding bone. Although titanium (TI) is regarded as a compatible implant material, increasing concern is coming up that the dissolved titanium particles induce inflammatory reactions around the implant. Specifically, the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) is expressed in the adjacent bone. The transition from TNF-α-induced local inflammation following insertion of DTI surgery to a chronic stage of "silent inflammation" could be a neglected cause of unexplained medical conditions. MATERIAL AND METHODS: The signaling pathways involved in the induction of cytokine release were analyzed by multiplex analysis. We examined samples of jawbone (JB) for seven cytokines in two groups: specimens from 14 patients were analyzed in areas of DTI for particle-mediated release of cytokines. Each of the adjacent to DTI tissue samples showed clinically fatty degenerated and osteonecrotic medullary changes in the JB (FDOJ). Specimens from 19 patients were of healthy JB. In five cases, we measured the concentration of dissolved Ti particles by spectrometry. RESULTS: All DTI-FDOJ samples showed RANTES/CCL5 (R/C) as the only extremely overexpressed cytokine. DTI-FDOJ cohort showed a 30-fold mean overexpression of R/C as compared with a control cohort of 19 healthy JB samples. Concentration of dissolved Ti particles in DTI-FDOJ was 30-fold higher than an estimated maximum of 1.000 µg/kg. DISCUSSION: As R/C is discussed in the literature as a possible contributor to inflammatory diseases, the here-presented research examines the question of whether common DTI may provoke the development of chronic inflammation in the jawbone in an impaired state of healing. Such changes in areas of the JB may lead to hyperactivated signaling pathways of TNF-α induced R/C overexpression, and result in unrecognized sources of silent inflammation. This may contribute to disease patterns like rheumatic arthritis, multiple sclerosis, and other systemic-inflammatory diseases, which is widely discussed in scientific papers. CONCLUSION: From a systemic perspective, we recommend that more attention be paid to the cytokine cross-talk that is provoked by dissolved Ti particles from DTI in medicine and dentistry. This may contribute to further development of personalized strategies in preventive medicine.

Autogenous fecal peritonitis in Wistar rats with permanent bilateral carotid occlusion: morbidity, mortality and microbiological response

PURPOSE: To investigate morbidity, mortality and microbiological response to fecal peritonitis induced in Wistar rats with permanent bilateral carotid ligation (PBCL). METHODS: Fecal peritonitis was induced in 30 rats, with 10 animals in each group: Group1 - normal young animals; Group2 - normal mature animals; and Group3 - rats with PBCL after four months postoperative follow-up. Peritonitis was induced with 10% stool suspension. Morbidity and mortality were evaluated. The survival animals after seven days were euthanized for tests. For microbiological studies blood were collected from the carotids and right ventricle; and fragments of lung and peritoneum. RESULTS: The morbidity and mortality of young animals were significantly lower than in mature animals with and without PBCL. There was no difference in morbidity and mortality among mature rats with and without PBCL. The diversity of microorganisms producing septicemia was similar to native micro biota of the large bowel. CONCLUSIONS: The immune response was more efficient in young animals, represented by significant less morbidity and no natural mortality. PBLC did not affect morbidity and mortality in mature rats. The immune response to fecal peritonitis has age as an independent predictor.