-
BMC Nephrology Jun 2024Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with...
BACKGROUND
Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities.
CASE PRESENTATION
A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient's sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient's sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases.
CONCLUSION
This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.
Topics: Humans; Glomerulonephritis, Membranous; Female; Middle Aged; Receptors, Phospholipase A2; Sarcoidosis; Genetic Predisposition to Disease; Autoantibodies
PubMed: 38937663
DOI: 10.1186/s12882-024-03649-0 -
Clinical and Experimental Medicine Jun 2024Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis... (Observational Study)
Observational Study
Comprehensive analysis of clinical outcomes, infectious complications and microbiological data in newly diagnosed multiple myeloma patients: a retrospective observational study of 92 subjects.
Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis incidence, causative pathogens, and impact on outcomes in newly diagnosed MM (NDMM) are limited. We conducted a retrospective observational study of 92 NDMM patients who developed sepsis between 2022 and 2023 at a tertiary care center in Italy. Patient characteristics, sepsis criteria [Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome (SIRS)], microbiology results, and associations with progression-free survival (PFS) were analyzed. In this cohort of 92 critically-ill patients, pathogenic organisms were identified via microbiological culture in 74 cases. However, among the remaining 18 culture-negative patients, 9 exhibited a SIRS score of 2 and another 9 had a SIRS score of 4, suggestive of a clinical presentation consistent with sepsis despite negative cultures. Common comorbidities included renal failure (60%), anemia (71%), and bone disease (83%). Gram-negative (28%) and Gram-positive (23%) bacteria were frequent causative organisms, along with fungi (20%). Cox Univariate analyses for PFS showed statically significant HR in patients with albumin ≥ 3.5 vs < 3.5 (HR = 5.04, p < 0.001), Karnofsky performance status ≥ 80 vs < 80 (HR = 2.01, p = 0.002), and early-stage vs late-stage disease by International Staging System (HR = 4.76 and HR = 12.52, both p < 0.001) and Revised International Staging System (R-ISS III vs R-ISS I, HR = 7.38, p < 0.001). Sepsis is common in NDMM and associated with poor outcomes. Risk stratification incorporating sepsis severity, comorbidities, and disease stage may help guide preventive strategies and optimize MM management.
Topics: Humans; Multiple Myeloma; Retrospective Studies; Male; Female; Aged; Middle Aged; Sepsis; Italy; Aged, 80 and over; Adult; Tertiary Care Centers
PubMed: 38937383
DOI: 10.1007/s10238-024-01411-2 -
Journal of Thrombosis and Haemostasis :... Jun 2024Acquired hemophilia A (AHA) is an autoimmune bleeding disorder caused by neutralizing antibodies against coagulation factor VIII (FVIII). Immunosuppressive therapy (IST)...
BACKGROUND
Acquired hemophilia A (AHA) is an autoimmune bleeding disorder caused by neutralizing antibodies against coagulation factor VIII (FVIII). Immunosuppressive therapy (IST) is standard of care to eradicate autoantibody production and protect from further bleeding but carries a risk of severe infection and mortality in frail patients with AHA. Recently, emicizumab has been studied for its potential to reduce the need for early and aggressive IST.
OBJECTIVE
To compare outcomes of two studies that used either IST (GTH-AH 01/2010; n=101) or prophylaxis with emicizumab (GHT-AHA-EMI; n=47) early after diagnosis of AHA.
METHODS
Baseline characteristics were balanced by propensity score matching. Primary endpoint was the rate of clinically relevant new bleeds during the first 12 weeks; secondary endpoints were adverse events and overall survival.
RESULTS
The negative binominal model-based bleeding rate was 68% lower with emicizumab as compared with IST (incident rate ratio 0.325, 95% confidence interval (CI) 0.182-0.581). No difference was apparent in the overall frequency of infections (emicizumab 21%, IST 29%) during the first 12 weeks, but infections were less often fatal in emicizumab treated patients (0%) compared with IST treated patients (11%). Thromboembolic events occurred less often with emicizumab (2%) than IST (7%). Overall survival after 24 weeks was better with emicizumab (90% versus 76%, HR 0.44; 95% CI 0.24-0.81).
CONCLUSION
Using emicizumab instead of IST in the early phase after initial diagnosis of AHA reduced bleeding and fatal infections, and improved overall survival.
PubMed: 38936699
DOI: 10.1016/j.jtha.2024.06.010 -
Cell Biochemistry and Function Jul 2024Butyrophilin (BTN) proteins are a type of membrane protein that belongs to the Ig superfamily. They exhibit a high degree of structural similarity to molecules in the B7... (Review)
Review
Butyrophilin (BTN) proteins are a type of membrane protein that belongs to the Ig superfamily. They exhibit a high degree of structural similarity to molecules in the B7 family. They fulfill a complex function in regulating immune responses, including immunomodulatory roles, as they influence γδ T cells. The biology of BTN molecules indicates that they are capable of inhibiting the immune system's ability to detect antigens within tumors. A dynamic association between BTN molecules and cellular surfaces is also recognized in specific contexts, influencing their biology. Notably, the dynamism of BTN3A1 is associated with the immunosuppression of T cells or the activation of Vγ9Vδ2 T cells. Cancer immunotherapy relies heavily on T cells to modulate immune function within the intricate interaction of the tumor microenvironment (TME). A significant interaction between the TME and antitumor immunity involves the presence of BTN, which should be taken into account when developing immunotherapy. This review explores potential therapeutic applications of BTN molecules, based on the current understanding of their biology.
Topics: Humans; Butyrophilins; Neoplasms; Immunomodulation; Immunotherapy; Tumor Microenvironment
PubMed: 38934382
DOI: 10.1002/cbf.4081 -
Frontiers in Immunology 2024Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising...
INTRODUCTION
Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3 T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3 T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3 T-lymphocytes.
METHODS
A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3 T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included.
RESULTS
Total lymphocyte counts below 0.3 x 10/L had a high sensitivity (86%) as a surrogate marker of CD3 T-lymphocytes below 0.05 x 10/L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 10/L as a surrogate marker for CD3 T-lymphocytes above 0.05 x 10/L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3 T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3 T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment.
DISCUSSION
Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 10/L whereas the CD3 T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment.
Topics: Humans; Antilymphocyte Serum; Lymphocyte Count; Retrospective Studies; Male; Female; Middle Aged; Adult; Graft Rejection; Immunosuppressive Agents; T-Lymphocytes; Kidney Transplantation; Aged; Pancreas Transplantation; CD3 Complex; Organ Transplantation
PubMed: 38933271
DOI: 10.3389/fimmu.2024.1419726 -
Frontiers in Immunology 2024Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but clinical implementation has been challenging. We...
Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but clinical implementation has been challenging. We previously showed that multivalent delivery of peptides as soluble antigen arrays (SAgAs) efficiently protects against spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Here, we compared the efficacy, safety, and mechanisms of action of SAgAs versus free peptides. SAgAs, but not their corresponding free peptides at equivalent doses, efficiently prevented the development of diabetes. SAgAs increased the frequency of regulatory T cells among peptide-specific T cells or induce their anergy/exhaustion or deletion, depending on the type of SAgA used (hydrolysable (hSAgA) and non-hydrolysable 'click' SAgA (cSAgA)) and duration of treatment, whereas their corresponding free peptides induced a more effector phenotype following delayed clonal expansion. Over time, the peptides induced an IgE-independent anaphylactic reaction, the incidence of which was significantly delayed when peptides were in SAgA form rather than in free form. Moreover, the N-terminal modification of peptides with aminooxy or alkyne linkers, which was needed for grafting onto hyaluronic acid to make hSAgA or cSAgA variants, respectively, influenced their stimulatory potency and safety, with alkyne-functionalized peptides being more potent and less anaphylactogenic than aminooxy-functionalized peptides. Immunologic anaphylaxis occurred in NOD mice in a dose-dependent manner but not in C57BL/6 or BALB/c mice; however, its incidence did not correlate with the level of anti-peptide antibodies. We provide evidence that SAgAs significantly improve the efficacy of peptides to induce tolerance and prevent autoimmune diabetes while at the same time reducing their anaphylactogenic potential.
Topics: Animals; Mice; Mice, Inbred NOD; Diabetes Mellitus, Type 1; Immune Tolerance; Peptides; Female; Autoantigens; T-Lymphocytes, Regulatory; Immunotherapy; Anaphylaxis; Desensitization, Immunologic
PubMed: 38933266
DOI: 10.3389/fimmu.2024.1258369 -
Vaccines Jun 2024Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and...
Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies, and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. Overall, 29.8% of PLWH had no SARS-CoV-2 serologic markers; they displayed significantly lower CD4 counts and higher HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG ( = 0.0003), anti-S IgA ( < 0.0001) and lack of neutralizing activity against the Omicron variant ( < 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immune responses but retained specific cellular immunity.
PubMed: 38932392
DOI: 10.3390/vaccines12060663 -
Viruses Jun 2024Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is... (Review)
Review
Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection.
Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus's direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection.
Topics: Simian Immunodeficiency Virus; Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Humans; HIV; Disease Models, Animal; Haplorhini; Lymphocyte Depletion
PubMed: 38932264
DOI: 10.3390/v16060972 -
Molecules (Basel, Switzerland) Jun 2024Ulcerative colitis (UC) is difficult to cure and easy to relapse, leading to poor quality of life for patients. Oxymatrine (OMT) is one of the main alkaloids of Aiton,...
Ulcerative colitis (UC) is difficult to cure and easy to relapse, leading to poor quality of life for patients. Oxymatrine (OMT) is one of the main alkaloids of Aiton, which has many effects, such as anti-inflammation, anti-oxidative stress, and immunosuppression. This study aimed to investigate whether OMT could attenuate ulcerative colitis by inhibiting the NOD-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis. In this study, the UC rat models were established by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) in vivo, while RAW264.7 cells and peritoneal macrophages were stimulated with Lipopolysaccharides/Adenosine Triphosphate (LPS/ATP) in vitro to simulate pyroptosis models, and Western blotting (WB) and other detection techniques were applied to analyze proteins involved in the NLRP3 inflammasome pathway. Our results showed that OMT alleviated colitis ulcers and pathological damage in the TNBS-induced UC rats and exhibited an inhibitory effect on pyroptosis at the early stage of UC. In the model group, the pyroptosis reached the peak at 24 h after modeling with the contents of active-cysteine-aspartic proteases-1 (caspase-1), Gasdermin D (GSDMD)-N, and cleaved-interleukin-1 beta (IL-1β) to the highest expression level. Meanwhile, we found that OMT (80 mg kg) remarkably decreased the expression levels of NLRP3, active-caspase-1, and cleaved-IL-1β at 24 h in the lesion tissue from UC rats. Further experiments on cells demonstrated that OMT at concentrations of 100 and 250 μM significantly inhibited cell death caused by NLRP3 inflammasome activation ( < 0.05), downregulated caspase-1, GSDMD, and decreased the levels of active-caspase-1, GSDMD-N, cleaved-IL-1β in RAW326.7 cells, and peritoneal macrophages. In summary, these results indicated that OMT could attenuate ulcerative colitis through inhibiting pyroptosis mediated by the NLRP3 inflammasome. The inhibition of the NLRP3 inflammasome may be a potential strategy for UC.
Topics: Animals; Quinolizines; Colitis, Ulcerative; Alkaloids; Pyroptosis; NLR Family, Pyrin Domain-Containing 3 Protein; Mice; Rats; Inflammasomes; RAW 264.7 Cells; Male; Disease Models, Animal; Rats, Sprague-Dawley; Trinitrobenzenesulfonic Acid; Lipopolysaccharides; Matrines
PubMed: 38930963
DOI: 10.3390/molecules29122897 -
Journal of Personalized Medicine Jun 2024Inflatable penile prosthesis (IPP) surgery is an effective treatment for erectile dysfunction (ED), but infections pose a significant threat to its success. Current... (Review)
Review
Inflatable penile prosthesis (IPP) surgery is an effective treatment for erectile dysfunction (ED), but infections pose a significant threat to its success. Current guidelines lack antifungal recommendations, despite rising fungal infection rates post-IPP surgery. This review examines epidemiology, risk factors (including diabetes mellitus, immunosuppression, and obesity), and pathogenesis, highlighting the role of biofilm formation in device contamination. Clinical manifestations vary from acute to delayed, with fungal biofilms presenting challenges in diagnosis. Prophylactic strategies, including broad-spectrum antibiotics and antifungals, are crucial, with evidence suggesting a 92% reduction in infections. With fungal infections showing lower salvage rates, management involves culture-guided treatment, irrigation, and oral antibiotics. Future research aims to understand biofilm mechanisms and develop biomaterials to reduce infection rates. Implementing antifungal therapy, along with standard practices like the no-touch technique and antibiotic dips, is crucial in preventing IPP infections.
PubMed: 38929865
DOI: 10.3390/jpm14060644