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Frontiers in Immunology 2023To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN).
OBJECTIVES
To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN).
METHODS
This retrospective study included 292 LN patients to determine HZ incidence during the last decades and its correlation with LN activity. LN patients with HZ were matched with LN patients without HZ in a 1:2 ratio based on sex, age, year of LN diagnosis, and LN histological class at kidney biopsy to assess HZ risk factors. Statistical tests included t-test, U-test, and Fisher's test. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors.
RESULTS
HZ occurred after LN diagnosis in 66 patients (prevalence 22.6%) with an average of 8.7 years (range 0.2-28.4 years). Although with the potential limitations of the retrospective nature and the extensive duration of the study, the incidence of HZ was 15.6/1,000 person-years, increasing from 6.9 before 1980 to 16.0 in the 1990s and 43.9 after 2010. HZ onset was unrelated to LN activity. LN was active in 43% of cases and quiescent in the other 57% of cases at HZ diagnosis. The percentage of patients who developed lupus flares during the year after HZ (18.9%) was not different from that which occurred during the year before HZ (17.2%, p = 0.804). After excluding confounding factors through matching, the univariate analysis suggested that cyclosporin during induction therapy (p = 0.011) and higher cumulative doses of glucocorticoids (GCs; >50 g, p = 0.004), cyclophosphamide (CYC; >5 g, p = 0.001), and mycophenolate mofetil (MMF > 1,000 g, p = 0.007) predisposed patients to HZ. Univariate and multivariate analyses revealed a protective role of azathioprine (p = 0.008) and methylprednisolone pulses (p = 0.010) during induction therapy.
CONCLUSIONS
HZ occurs unpredictably throughout the course of LN, underscoring the importance of continuous monitoring for these patients. In addition, the incidence of HZ seems to have increased in recent decades. Induction therapy with azathioprine and methylprednisolone pulses appears to provide protection, while higher cumulative doses of GCs, CYC, and MMF increase susceptibility.
Topics: Humans; Lupus Nephritis; Immunosuppressive Agents; Azathioprine; Retrospective Studies; Treatment Outcome; Mycophenolic Acid; Herpes Zoster; Methylprednisolone
PubMed: 38077357
DOI: 10.3389/fimmu.2023.1293269 -
Chinese Medical Journal Jan 2024Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased... (Review)
Review
Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.
Topics: Humans; Calcineurin Inhibitors; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid
PubMed: 38057972
DOI: 10.1097/CM9.0000000000002959 -
GeroScience Feb 2024In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12%...
Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used.
In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang-Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.
Topics: Female; Mice; Male; Animals; Longevity; Meclizine; Hydrogen Sulfide; Dimethyl Fumarate; Mycophenolic Acid; Phenylbutyrates; Xanthophylls; Flavonols
PubMed: 38041783
DOI: 10.1007/s11357-023-01011-0 -
RMD Open Nov 2023To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease. (Clinical Trial)
Clinical Trial
COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series.
OBJECTIVE
To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease.
METHODS
We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed.
RESULTS
Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2-53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection.
CONCLUSION
In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.
Topics: Adult; Humans; 2019-nCoV Vaccine mRNA-1273; Autoimmune Diseases; COVID-19; COVID-19 Vaccines; Lupus Erythematosus, Systemic; Mycophenolic Acid; Prospective Studies; Rheumatic Diseases; Rituximab
PubMed: 38030231
DOI: 10.1136/rmdopen-2023-003400 -
Clinical Case Reports Nov 2023The immunosuppressant agents should be considered earlier in the course of treatment with rituximab, possibly after the unfavorable response at first cycle of treatment,...
KEY CLINICAL MESSAGE
The immunosuppressant agents should be considered earlier in the course of treatment with rituximab, possibly after the unfavorable response at first cycle of treatment, especially in male patients and those with high BMI.
ABSTRACT
Rituximab (RTX) has recently been proposed as an alternative first-line therapy for pemphigus patients. However, there are some rare reports of worsening of pemphigus following RTX therapy in the literature. This study aimed to evaluate the efficacy and safety of using a combination treatment of mycophenolate mofetil or dapsone and methotrexate in case of nonresponse, exacerbation or development of allergic reactions following rituximab therapy in pemphigus patients. In this case series, archive files of pemphigus patient in a tertiary care hospital from 2016 to 2021 who were treated with rituximab were reviewed and those with failure in treatment process including nonresponsiveness, exacerbation or development of allergic reactions to rituximab were identified and assessed. The study includes five patients out of 1245 RTX-treated patients, who did not respond to RTX (one patient) or experienced an exacerbation of disease (two patients) or development of allergic reactions (two patients). Male patients with high BMI (BMI > 25) whose response to rituximab was not good at first cycle and happened to receive rituximab later in the course of disease, had highest number of relapses and benefited the most from this combination immunosuppressive treatment as an alternative for repeating rituximab cycles. The lower risk of relapse and a better chance of remission might indicate the efficacy of adjuvant immunosuppressant therapy in patients with no-response, exacerbation, or allergic reaction to rituximab. These therapeutic effects were better observed in patients who received lower doses of rituximab which could suggest that the immunosuppressant agents should be considered earlier in the course of the disease, possibly after the first failed trial of rituximab therapy.
PubMed: 38028089
DOI: 10.1002/ccr3.8208 -
Respiratory Investigation Jan 2024Solid organ transplant (SOT) recipients with coronavirus disease-2019 (COVID-19) experience prolonged viral shedding, and they are forced to stay in the hospital because...
Solid organ transplant (SOT) recipients with coronavirus disease-2019 (COVID-19) experience prolonged viral shedding, and they are forced to stay in the hospital because of the requirement for COVID-19 isolation. Here, we present two cases (lung and renal transplant recipients), wherein the isolation period was shortened by reducing the dosage of mycophenolate mofetil (MMF). Both patients recovered well from COVID-19 pneumonia. This case study suggests that a reduction in MMF dosage may lead to a shorter hospitalization period in SOT recipients with COVID-19.
Topics: Humans; Mycophenolic Acid; COVID-19; Immunosuppressive Agents; Virus Shedding; Kidney Transplantation
PubMed: 38016402
DOI: 10.1016/j.resinv.2023.10.006 -
Fa Yi Xue Za Zhi Oct 2023The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI)...
OBJECTIVES
The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI.
METHODS
The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in.
RESULTS
Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 () gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (), integrin subunit alpha 1 (), and H2B clustered histone 5 () were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid.
CONCLUSIONS
, and may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.
Topics: Humans; Infant; Gene Expression Profiling; Sudden Infant Death; Gene Regulatory Networks; Protein Interaction Maps; Computational Biology
PubMed: 38006261
DOI: 10.12116/j.issn.1004-5619.2022.420803 -
Vaccines Oct 2023Renal transplant recipients (RTRs) tend to mount weaker immune responses to vaccinations, including vaccines against the novel severe acute respiratory syndrome...
BACKGROUND
Renal transplant recipients (RTRs) tend to mount weaker immune responses to vaccinations, including vaccines against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS
Humoral immunity was assessed using anti-receptor binding domain (RBD) and neutralizing antibodies (NAb) serum levels measured by ELISA, and cellular immunity was assessed using T-, B-, NK, natural killer-like T (NKT)-cell subpopulations, and monocytes measured by flow cytometry, and also specific T-cell immunity, at predefined time points after BNT162b2 vaccination, in 57 adult RTRs.
RESULTS
Administration of three booster doses was necessary to achieve anti-RBD and NAb protective levels in almost all patients (92.98%). Ab production, at several time points, was positively correlated with the corresponding renal function and inversely correlated with hemodialysis vintage (HDV) and treatment with mycophenolic acid (MPA). A gradual rise in several cell subpopulations, including total lymphocytes ( = 0.026), memory B cells ( = 0.028), activated CD4 ( = 0.005), and CD8 cells ( = 0.001), was observed even after the third vaccination dose, while a significant reduction in CD3+PD1+ ( = 0.002), NKT ( = 0.011), and activated NKT cells ( = 0.034) was noted during the same time interval. Moreover, SARS-CoV-2-specific T-cells were present in 41% of the patients who were unable to develop Nabs, and their positivity rates four months after the second dose were in inverse correlation with monocytes ( = 0.045) and NKT cells ( = 0.01).
CONCLUSIONS
SARS-CoV-2-specific T-cell responses preceded the humoral ones, while two booster doses were needed for this group of immunocompromised patients to mount a protective immune response.
PubMed: 38006002
DOI: 10.3390/vaccines11111670 -
Zhongguo Dang Dai Er Ke Za Zhi =... Nov 2023To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis...
OBJECTIVES
To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups.
METHODS
A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (=30), the >12 years MMF subgroup (=15), the ≤12 years CTX subgroup (=71), and the >12 years CTX subgroup (=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions.
RESULTS
There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (<0.05).
CONCLUSIONS
The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.
Topics: Child; Humans; Mycophenolic Acid; IgA Vasculitis; Retrospective Studies; Cyclophosphamide; Immunosuppressive Agents; Vasculitis; Nephritis
PubMed: 37990454
DOI: 10.7499/j.issn.1008-8830.2306085 -
Medicine Nov 2023Evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) for renal transplantation (RT) is still limited, but...
Clinical impact using low-dose mycophenolate mofetil with tacrolimus on infectious, noninfectious complications and acute rejection, in renal transplant: A single hospital experience in Mexico.
Evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) for renal transplantation (RT) is still limited, but maintaining a dose of <2 g could result in worse clinical outcomes in terms of acute rejection (AR). This study aimed to determine the association between AR and infectious and noninfectious complications after RT with a dose of 1.5 g vs 2 g of MMF. A prospective cohort study was performed with a 12-month follow-up of recipients of RT from living donors with low (1.5 g/day) or standard (2 g/day) doses of MMF. The association between adverse effects and complications and doses of MMF was examined using Cox proportional hazard models, and survival free of AR, infectious diseases, and noninfectious complications was evaluated using the Kaplan-Meier test. At the end of the follow-up, the incidence of infectious diseases was 52% versus 50% (P = .71) and AR was 5% versus 5% (P = .86), respectively. The survival rate free of gastrointestinal (GI) complications requiring medical attention was higher in the low-dose group than in the standard-dose dose (88% vs 45%, respectively; P < .001). The use of 1.5 g/day of MMF confers a reduction in GI complications without an increase in infectious diseases or the risk of AR.
Topics: Humans; Tacrolimus; Mycophenolic Acid; Immunosuppressive Agents; Kidney Transplantation; Mexico; Prospective Studies; Drug Therapy, Combination; Communicable Diseases; Hospitals; Graft Rejection; Graft Survival
PubMed: 37986377
DOI: 10.1097/MD.0000000000035841