Immunosuppressive Research Articles

Thrombotic thrombocytopenic purpura: 100 years of research on Moschcowitz syndrome

AbstractIn the 100 years since Eli Moschcowitz reported the first case of thrombotic thrombocytopenic purpura (TTP), there has been remarkable awareness and progress in the diagnosis and management of this rare blood disorder. This progress initially was the result of careful clinical observations followed by well thought-out therapeutic interventions, with dual goals of both improving outcomes and discerning the pathophysiology of TTP. The discovery of the ADAMTS13 protease set in motion the efforts to more accurately define the specific etiologies of thrombotic microangiopathies (TMAs) based on objective, scientific data rather than clinical characterizations alone. This accurate differentiation led to better and more revealing clinical trials and advancements in the treatment of TTP and other TMAs. Further advances followed and included improvements in immune-suppressive therapy and targeted therapies of immune-mediated TTP (iTTP; caplacizumab) and congenital TTP (cTTP; recombinant ADAMTS13). The longitudinal study of patients with TTP revealed the unexpected risk for long-term complications in both patients with iTTP and those with cTTP in remission. Ongoing studies aim to further understand the prevalence, mechanisms, and appropriate screening for these mood disorders, neurocognitive deficits, and cardiovascular complications that develop at remarkably high rates and are associated with a decreased life expectancy. These discoveries are a result of the collaborative efforts of investigators worldwide that have been fostered by the frequent interactions of investigators via the International TTP Working Group meetings and TMA workshops held regularly at international meetings. These efforts will support the rapid pace of discovery and improved understanding of this rare disease.

Immunogenicity and Adverse Events after Covid-19 Vaccination in Patients with Systemic Inflammatory Autoimmune Diseases

Abstract Background The first cases of COVID-19 began in Wuhan, Hubei Province china, in December 2019. Since then, this disease caused by a highly pathogenic virus, severe acute respiratory syndrome coronavirus (SARS-COV-2), has been labelled as a global pandemic. It is believed that the primary means of viral spread is via respiratory droplets during close-range, human-to-human contact. Aim of the Work To assess immunogenicity and to compare adverse effect following COVID-19 vaccinations in patients with systemic inflammatory autoimmune diseases vs matched healthy controls. Patients and Methods This is a cross sectional study. Two groups of subjects were enrolled in the study after consideration of both inclusion and exclusion criteria. Group A: patients with systemic inflammatory auto immune disease (60 subjects) including (30 patients with systemic lupus erythematosus, 30 patients with rheumatoid arthritis) who received two doses of COVID-19 vaccine. Group B: age-matched healthy controls who received two doses of COVID-19 vaccine (30 Subjects). All patients were recruited from the outpatient clinic of department of Internal Medicine – Rheumatology division at Ain Shams University Hospital. Control group were recruited from medical and non-medical staff working at Ain Shams University Hospital. Results There was no statistically significant difference in the titre of anti-spikes antibodies with the use of different immune suppressive drugs in RA group such as methotrexate and leflunomide with p-value =0.935,0.257, respectively,also in SLE patients there was no statistically significant difference in the titre of anti-spikes antibodies with the use of different immune suppressive drugs in SLE group such as azathioprine, mycophenolate mofetil and cyclophosphamide with p-value = 0.317, 1.000 and 0.513 respectively,(all patients in our study were on corticosteroids and hydroxychloroquine). There was statistically significant difference as regarding disease activity in RA patients before and after covid-19 vaccine with p-value = 0.001,with a total percentage of 26.70% of patients developed mild disease activity,13.30% developed moderate disease activity while 3.3% of patients developed severe activity and as regarding SLE patients there was statistically significant difference as regarding disease activity in SLE patients before and after covid-19 vaccine with p-value = 0.002,with a total percentage of 23.3% of patients developed mild disease activity,6.7% developed moderate disease activity while 10% of patients developed severe activity. Conclusion Comparable side effects in both control and patients group with only minor side effects were reported. The Sinopharm BIBP COVID-19 vaccine was immunogenic in the majority of patients in comparison to control group, with an acceptable safety profile. The use of different immune suppressive therapies (methotrexate, azathioprine, mycophenolate mofetil,cyclophosphamide) didn’t affect humoral response after two doses of the vaccine. Apparent impact on disease activity of both SLE and RA patients but mainly in the form of mild disease activity.

Immunogenicity and Adverse Events after Covid-19 Vaccination in Patients with Systemic Inflammatory Autoimmune Diseases

Abstract Background The first cases of COVID-19 began in Wuhan, Hubei Province china, in December 2019. Since then, this disease caused by a highly pathogenic virus, severe acute respiratory syndrome coronavirus (SARS-COV-2), has been labelled as a global pandemic. It is believed that the primary means of viral spread is via respiratory droplets during close-range, human-to-human contact. Aim of the Work To assess immunogenicity and to compare adverse effect following COVID-19 vaccinations in patients with systemic inflammatory autoimmune diseases vs matched healthy controls. Patients and Methods This is a cross sectional study. Two groups of subjects were enrolled in the study after consideration of both inclusion and exclusion criteria. Group A: patients with systemic inflammatory auto immune disease (60 subjects) including (30 patients with systemic lupus erythematosus, 30 patients with rheumatoid arthritis) who received two doses of COVID-19 vaccine. Group B: age-matched healthy controls who received two doses of COVID-19 vaccine (30 Subjects). All patients were recruited from the outpatient clinic of department of Internal Medicine – Rheumatology division at Ain Shams University Hospital. Control group were recruited from medical and non-medical staff working at Ain Shams University Hospital. Results There was no statistically significant difference in the titre of anti-spikes antibodies with the use of different immune suppressive drugs in RA group such as methotrexate and leflunomide with p- value = 0.935,0.257, respectively,also in SLE patients there was no statistically significant difference in the titre of anti-spikes antibodies with the use of different immune suppressive drugs in SLE group such as azathioprine, mycophenolate mofetil and cyclophosphamide with p-value = 0.317, 1.000 and 0.513 respectively,(all patients in our study were on corticosteroids and hydroxychloroquine). There was statistically significant difference as regarding disease activity in RA patients before and after covid-19 vaccine with p-value = 0.001,with a total percentage of 26.70% of patients developed mild disease activity,13.30% developed moderate disease activity while 3.3% of patients developed severe activity and as regarding SLE patients there was statistically significant difference as regarding disease activity in SLE patients before and after covid-19 vaccine with p-value = 0.002,with a total percentage of 23.3% of patients developed mild disease activity, 6.7% developed moderate disease activity while 10% of patients developed severe activity. Conclusion Comparable side effects in both control and patients group with only minor side effects were reported. The Sinopharm BIBP COVID-19 vaccine was immunogenic in the majority of patients in comparison to control group, with an acceptable safety profile. The use of different immune suppressive therapies (methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide) didn’t affect humoral response after two doses of the vaccine. Apparent impact on disease activity of both SLE and RA patients but mainly in the form of mild disease activity.

Significant Long-Term Prevention of High Sensitization After Kidney Allograft Failure by Maintaining Calcineurin Inhibitor-Based Immunosuppression.

Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF). Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127). Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0%vs. 85.5%, p < 0.001) and 24 months (61.0%vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4%vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6%vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9%vs. 18.6%, p=0.003, OR=0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406vs. 813 days, p = 0.001) without an increased risk of complications. CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.

Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.

Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted and effector memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease. Thus, JAK inhibition may improve the efficacy of anti-PD-1 immunotherapy by pivoting T cell differentiation dynamics.

Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.

#2992 Risk and prognostic factors for post-transplantation lymphoproliferative disease in solid organ transplant recipients—a multicenter analysis

Abstract Background and Aims Post-transplantation lymphoproliferative disorder (PTLD), a potentially fatal complication of transplantation, affects solid organ transplant recipients at different rates, depending on organ graft type: the risk greater in lung transplant recipients (LngTRs), lower for liver transplant recipients (LTRs) and lowest for kidney transplant recipients (KTR). In this study we aimed to investigate the factors affecting the development and treatment outcomes of PTLD and compare their effect on KTRs, LTRs and LngTRs. Method In this retrospective cohort study we have included all KTRs, LTRs and LngTRs diagnosed with PTLD at six transplantation centers in Poland. The data collected from medical records included: immunosuppression (IS), viral infections, PTLD type, treatment and outcomes. Chi-squared test was used to assess the differences in group composition. To determine the impact of variables upon PTLD time of onset and patient survival, univariate Cox regression was used. p-values below 0.05 were considered statistically significant. Results We enrolled 50 KTRs, 36 LTRs and 5 LngTRs from 6 transplantation centers in Poland. Based on the data from the most contributing centers in each group, the prevalence of PTLD was 0.82% of KTRs, 2.03% LTRs and 1.51% of LngTRs. Two thirds of the enrolled patients were male, the median age at first transplantation was 40 years for KTRs, 45 for LTRs and 25 for LngTRs (Table 1). The groups significantly differed in IS treatment: steroid (GCS) and cyclosporin (CsA) use was more frequent in KTRs (p&amp;lt;0.001 and p&amp;lt;0.001 and respectively), tacrolimus (TAC) and anti-CD25 induction in LTRs (p ≤ 0.001 and p&amp;lt;0.001 respectively), sirolimus (RAPA) in LngTRs (p&amp;lt;0.001). KTRs were the latest to develop PTLD (126 months after transplantation, p&amp;lt;0.001). In all groups Monomorphic B-cell PTLD was the most frequent. Initial IS treatment reduction was used in 80-86% of patients, R-CHOP chemotherapy was most common in LTRs (p=0.021), other chemotherapy regimens in KTRs (p=0.031). TAC had the opposite effect on PTLD time of onset in KTRs (HR=2.18, p=0.013) and LTRs (HR=0.18, p=0.036). The overall survival at the end of observation period was 26% for KTRs, 58% for LTRs and 80% for LngTRs. Loss to follow up was most frequent in KTRs at 26%. Patient survival was not affected by PTLD treatment. Conclusion KTRs develop PTLD later than LTRs and LngTRs, and time of disease onset is associated with TAC use. Lower survival in KTRs may result from the longer follow-up period compared to other solid organ transplant recipients.

The value of extracorporeal photopheresis as an immunosuppression-modifying approach in solid organ transplantation: a potential solution to an unmet medical need

Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.

#2149 Kidney transplantation outcomes in lupus nephritis

Abstract Background and Aims Kidney transplantation (KT) is the renal replacement therapy of choice in patients with lupus nephritis (LN) who progress to end-stage renal disease (ESRD). The latest Spanish guidelines recommend the use of hydroxychloroquine after KT in these patients. Our study aims to analyze KT outcomes in patients with LN in our center. Method Retrospective cohort study, which included all KT with a diagnosis of LN who underwent KT between April 1982 and November 2023 at Puerta del Mar University Hospital (Spain). Each KT recipient with LN was matched with two controls from the same institution by age, sex and type of donor during the same period. We collected clinical and demographical characteristics, as well as immunosuppressive (IS) therapy after KT. We analyzed the death-censored graft survival and patient survival and compiled the causes of death and graft loss, comparing them with the control group. We documented LN recurrences, KT rejections, and incidence of CMV and BK infection. Results In this period, 2055 KTs were performed in our center, of which 39 had a diagnosis of LN (1.9%). Seventy eight controls were selected. The majority of KTs were women (89.7%) with a mean age of 44 years. Induction therapy was used in 85.2% of KT with Thymoglobulin (63%) or Basiliximab (27%). Maintenance IS therapy was based on tacrolimus (93.5%), cyclosporine (6.5%), mycophenolate (100%) and prednisone (100%). Only 4 patients (10.2%), the latest ones, received hydroxychloroquine after KT. Death-censored graft survival at 1 year (87.1% SLE vs. 88.5% Non-SLE), 5 years (74.9% SLE vs. 80.8% Non-SLE), and 10 years (65.6% SLE vs. 69.5% Non-SLE) and patient survival at 1 year (97.1% SLE vs. 100% Non-SLE), 5 years (93.7% SLE vs. 95.3% Non-SLE), and 10 years (93.7% SLE vs. 91.7% Non-SLE) were similar in both groups. No graft was lost because of recurrent LN. No significant differences were found neither in the causes of death nor between the causes of graft loss. The incidence of CMV and BK infection and KT rejection rates were similar in both groups. Conclusion KT is an excellent therapeutic alternative in LN with ESRD. Despite the low use of hydroxychloroquine in our series, no recurrence of LN was detected and the KT outcomes were similar to the control group.

#1927 Efficacy and safety of ripertamab in paediatic glomerular disease

Abstract Background and Aims Anti-B-cell treatment has been shown to be an efficient tactic for glomerular disease. Ripertamab as a novel anti-CD20 monoclonal antibody developed by China, has been structurally optimized to specifically bind to the transmembrane antigen CD20, with an amino acid difference in the constant region sequence compared to rituximab. This study reports the efficacy and safety of ripertamab in children with different glomerular diseases. Method We retrospectively report the data of 140 children with a diagnosis of glomerular disease and a treatment with ripertamab in a single center Results A total of 140 children (age, 11.2 ± 3.7 years; 58.6% boys) were included, 69/140 (49.3%) steroid-dependent nephrotic syndrome (SDNS), 38/140 (27.1%) steroid-resistant but CNIs-dependent nephrotic syndrome, 18/140 (12.9%) Lupus nephritis, 5/140 (3.6%) atypical hemolytic uremic syndrome, 4/140 (2.9%) ANCA associated vasculitis, 3/140 (2.1%) membranous nephropathy and 3/140 (2.1%) IgA vasculitis nephritis. The Median (IQR) duration of disease before the application of ripertamab was 4.4 (2.3, 7.4) years. They totally received 200 courses of ripertamab. A total of 83, 55, 1, and 1 patient received one, two, three, and four courses, respectively. Ripertamab 375 mg/m2 (maximum 500 mg) were injected per course. B cell depletion could be observed in 129/140 (92.1%) children one month after ripertamab. An additional course was administered due to recovery of B-cells or relapse. Median (IQR) follow-up was 0.8 (0.5, 1.1) years. The median relapse-free period after the first course was 4.7 months (IQR, 3.8, 5.6 months). Most of the relapses developed simultaneously with recovery of B-cells. About 36.7% of these children stopped steroid during the follow-up. One or more immunosuppressant (IS) drugs needed before ripertamab infusion could be withdrawn or reduced in 109/140 patients (77.9%). None of the patients developed life-threatening adverse events. Conclusion This study suggests that ripertamab could be an effective and safe treatment for various pediatric glomerular diseases.

The Effects of Sustained Immunosuppression Withdrawal After Liver Transplantation on Metabolic Syndrome.

Liver transplant (LT) recipients often experience adverse effects of immunosuppressive (IS) drugs, especially on metabolic profiles. Selected LT recipients can achieve successful IS withdrawal; however, its effects on metabolic syndrome (MS) are unknown. This is a retrospective single-center study investigating the incidence and/or regression of MS in 75 selected LT recipients who were previously enrolled in prospective IS withdrawal trials between 1999 and 2017. Patients who were transplanted due to nonalcoholic steatohepatitis/metabolic-associated fatty liver disease were excluded, as well as those with a follow-up <3 y after IS weaning. Forty-four patients (58.7%) achieved sustained withdrawal or minimization of immunosuppression (WMIS) and 31 patients (41.3%) required reintroduction of immunosuppression (no-WMIS). Among LT recipients who were metabolically healthy (n = 52, 69.3%) before the start of IS weaning, there was a significantly lower rate of de novo MS in WMIS patients compared with no-WMIS patients after 5 y (8.3% and 47.8%, respectively, P = 0.034). Of 23 LT recipients (30.7%) who had MS at the time of commencing IS withdrawal, complete regression of MS was observed in 47.1% of WMIS patients and in none (0%) of the no-WMIS patients after 5 y (P = 0.054). Furthermore, individual components of MS were better controlled in IS-weaned patients, such as arterial hypertension and abnormal serum lipids. Achievement of sustained IS withdrawal reduces the incidence of de novo MS development in metabolically healthy patients and increases the likelihood of MS regression in patients with established MS. The foreseeable long-term beneficial effects of these favorable metabolic changes on morbidity and mortality of LT recipients require further investigation.

Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

BackgroundDespite impaired humoral responses in patients treated with immunosuppressants (ISPs), recent studies found similar severity of SARS-CoV-2 breakthrough infections compared to controls. One potential explanation is the rapid generation humoral responses upon infection, but evidence is lacking. ObjectivesTo investigate longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infections in patients with immune-mediated inflammatory diseases (IMID) on ISPs and controls. MethodsAs prospective sub-study of the national Target-to-B! (T2B!) consortium, we included IMID patients on ISPs and controls who reported SARS-CoV-2 breakthrough infections between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, three antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at four time points after SARS-CoV-2 breakthrough infections. ResultsWe included 302 IMID patients on ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infections in both groups. However, in IMID patients on anti-CD20 therapy and sphingosine-1 phosphate receptor (S1P) modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild and hospitalization was required in less than 1% of the cases. ConclusionsMost ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones towards new viral variants. However, in patients treated with anti-CD20 therapy or S1P modulators, the dynamics were greatly impaired, and to a lesser extent in those anti-TNF. Nevertheless, only a few severe breakthrough cases were reported.

Mohs micrographic surgery in immunosuppressed vs immunocompetent patients: Results of a prospective nationwide cohort study (REGESMOHS, Spanish registry of Mohs surgery).

Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.

Factors associated with drug retention of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: A multicentre REVEAL cohort study.

To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

Increased incidence and mortality from Listeria monocytogenes infection in Spain

ObjectivesListeria monocytogenes (LM) is a health threat worldwide given its high mortality and the growing of high-risk susceptible populations. MethodsAll hospitalizations with a diagnosis of LM in the National Registry of Hospital Discharges were examined in Spain from 2000 to 2021. ResultsA total of 8152 hospital admissions with LM were identified. The mean age was 59.5 years and 48% were immunosuppressed (IS).The rate of LM hospitalizations increased from 5 per 1 million population in 2000 to 8.9 in 2021 (p < 0.001). A foodborne outbreak in Andalusia determined a sharp increase in admissions with LM during 2019. The COVID-19 pandemic and lockdowns were associated with a decrease in LM admissions.The overall in-hospital mortality was 16.7%. The number of deaths in patients hospitalized with LM rose from 7.8 per 100,000 deceased in 2000 to 18 in 2021 (p < 0.001). After adjustment, age >65 years (odds ratio [OR] = 2.16), sepsis (OR = 2.60), meningoencephalitis (OR = 1.72), endocarditis (OR = 2.0), neonatal listeriosis (OR = 2.10) and IS (OR = 2.09) were associated with mortality. ConclusionsThe number of patients hospitalized with LM in Spain has increased significantly from 2000 to 2021. The increase in the rate of admissions and deaths was largely driven by the growing proportion of elderly and IS patients.

Management of immunosuppressive therapy after functional renal graft failure: results of a practice survey of French-speaking nephrologists

The management of patients with kidney transplant failure (KTF) remains a complex process involving multiple stakeholders. A working group of the Transplantation Commission of the French-speaking Society of Nephrology, Dialysis and Transplantation (SFNDT) conducted a survey on the management of immunosuppressants (IS) after KTF among nephrologists at transplant centres and general nephrologists in France, Switzerland and Belgium between March and June 2023. We analysed 232 replies from 58 nephrologists at transplant centres and 174 general nephrologists, aged 43.6 (+10.6) years. In the first three months following KTF, nephrologists reported discontinuing antimetabolite, calcineurin inhibitor (CNI) and corticosteroid treatment in 83%, 39.9% and 25.8% of cases respectively. Conversely, some nephrologists reported that they were continuing to use CNI (14%) and corticosteroids (19.1%) on a long-term basis. The patient’s comorbidities associated with the discontinuation of IS treatment are cancer and opportunistic infections as KT’s complications and presence of diabetes mellitus at KTF, whereas humoral rejection encourages the IS to be maintained. Transplantectomy is proposed by nephrologists most often for graft intolerance syndrome (86.5%), more rarely to discontinue IS (17.6%) or in the absence of plans of new transplantation (9.3%). In multivariate analyses, the presence of a protocol in the centre facilitated the management of IS by the general nephrologists. The management of IS after AFG by French-speaking nephrologists is heterogeneous. Specific prospective studies are needed to establish new best practice recommendations, based on more robust evidence, which could encourage better adherence by nephrologists.

Impact of immunosuppressive agents on the management of immune-related adverse events of immune checkpoint blockers

BackgroundImmune checkpoint blockers (ICBs) can induce immune-related adverse events (irAEs) whose management is based on expert opinion and may require the prescription of steroids and/or immunosuppressants (ISs). Recent data suggest that these treatments can reduce the effectiveness of ICBs. ObjectiveTo investigate the relationship between the use of steroids and/or ISs and overall survival (OS) and progression-free survival (PFS) among ICB-treated patients with an irAE. MethodsWe prospectively collected data from the medical records of patients with solid tumors or lymphoma in the French REISAMIC cohort and who had been treated with ICBs between June 2014 and June 2020. Results184 ICB-treated patients experienced at least one Common Terminology Criteria for Adverse Events grade ≥ 2 irAE. 107 (58.2%) were treated with steroids alone, 20 (10.9%) with steroids plus IS, 57 (31.0%) not received steroids or IS. The median OS was significantly shorter for patients treated with steroids alone (25.2 months [95% confidence interval (CI): 22.3–32.4] than for patients treated without steroids or IS (63 months [95%CI: 40.4-NA]) and those receiving an IS with steroids (53.4 months [95%CI: 47.3-NA]) (p < 0.001). The median PFS was significantly shorter for patients treated with steroids alone (17.0 months [95%CI: 11.7–22.9]) than for patients treated without steroids or IS (33.9 months [95%CI: 18.0-NA]) and those receiving an IS with steroids (41.1 months [95%CI: 26.2-NA]) (p = 0.006). There were no significant intergroup differences in the hospital admission and infection rates. ConclusionIn a prospective cohort of ICB-treated patients, the use of IS was not associated with worse OS or PFS, contrasting with the use of steroids for the management of irAEs.

Lupus Nephritis Outcomes after Stopping Immunosuppression.

Background/Objectives: Immunosuppression (IS) is a standard therapy for lupus nephritis (LN). Data on the outcomes of patients with LN after the discontinuation of immunosuppression remain uncertain. This study aimed to evaluate the outcomes and results of patients with lupus nephritis (LN) who ceased immunosuppressive (IS) therapy. Methods: Records were obtained on the clinical and laboratory features of LN patients who were treated at our Lupus Unit. They included median values and ranges for various numerical variables such as patient age, disease duration, and treatment duration. Categorical variables such as gender, LN class, IS treatment type, and patient outcomes, which were categorized as either "stable" or "flare experienced", were presented as percentages and frequencies. A flare in LN was characterized by a two-fold increase in serum creatinine levels and a rise in proteinuria following the cessation of IS medication. Results: Outcomes were assessed for 45 patients with LN who ceased IS therapy after achieving remission. The patients' median age was 55 years (29-78). The median duration of treatment was 4 years (0.5-14). The LN histology distribution was class V = 24.4%, class IV = 17.8 %, class III = 17.8%, class III + IV = 15.6%, class III + V = 6.7%, class IV + V = 2.2%, and class II + IV and II = 2.2%. At the discontinuation of IS treatment, creatinine levels were elevated in 9/45 (20%) patients. Furthermore, 28.9% of patients relapsed after IS treatment discontinuation. Patients with anti-Smith antibodies (anti-Sm) were observed to have a higher occurrence of relapses, with six patients experiencing flare compared to four patients who remained stable (p = 0.03). Five (38.5%) of the patients with flares had high creatinine levels after IS discontinuation. Conclusions: Most of our patients maintained clinical remission and stable levels of LN parameters after IS treatment discontinuation. Those with a high serum creatinine level, ongoing proteinuria, depleted complement levels, and the presence of anti-Sm antibodies were more likely to experience flares after the discontinuation of IS therapy.

Progress in research and treatment of immune checkpoints in breast cancer

Breast cancer is the most common malignant tumor among women often involving the toxicity of conventional chemotherapy alongside organ-specific side effects. As immunotherapeutic agents in anti-tumor, new immune checkpoints are constantly being dug and discovered. The role of immune checkpoint inhibitors in the process of tumor immune evasion has assumed increasing significance. Currently, clinical research outcomes on immunotherapy for breast cancer vary, reflecting diverse efficacy profile of immune checkpoints. This article provides an overview of immune checkpoint suppression therapy, and track the evolving research and therapeutic application of immune checkpoints related to breast cancer.

Quality of life after immune suppressive therapy in aplastic anemia.

Acquired aplastic anemia (AA) is a rare form of immune-mediated bone marrow failure, which can result in life-threatening infections or bleeding if left untreated. Treatment consists of either immune suppressive therapy (IST) or allogeneic stem cell transplantation (alloHSCT). While considerable research has been published regarding survival, response rate and toxicity of both treatments, knowledge on the impact on quality of life (QoL) is scarce. We used the recently developed AA-specific QoL questionnaire (QLQ-AA/PNH-54) to evaluate QoL in a single center cohort of AA patients who were successfully treated with IST. The 54 questions represent 12 different QoL domains. Results were analyzed for all patients and grouped based on hematologic response (complete response (CR) or partial response (PR)). Thirty-six successfully treated adult patients (15 in CR, 21 in PR) completed the questionnaire (median age 54years, range 21-71; median time since last IST 5years, range 0-41). Fatigue was experienced by 83% of patients. Even though total QoL scores did not significantly differ between patients with PR and CR (105 vs 92, p-value 0,17) there appeared to be a trend towards higher scores in patients with PR, especially in domains concerning psychological wellbeing. This trend was most clear in the domains fear of progression (2,12 in PR patients vs 1,73 in CR patients; p-value 0,08) and role functioning (2,22 vs 1,88; p-value 0,07). In conclusion, patients with AA continue to experience psychological and physical effects despite successful IST.