Conventional Immunosuppressive Therapy Research Articles

#3108 Rituximab in adult-onset IgA vasculitis

Abstract Background and Aims Adult-onset IgA Vasculitis (IgAV) is poorly responsive to glucocorticoids (GC) and conventional immunosuppressive therapies, such as cyclophosphamide. Rituximab has been successfully used in a few cases and may represent a safer and potentially more effective option [1]. Crescentic IgA Nephropathy (cIgAN), a rare entity that shares features of renal vasculitis with IgAV, is also frequently refractory to cyclophosphamide, while response to rituximab is unknown. We investigated outcomes after rituximab in a multicentre European cohort of adult-onset IgAV and cIgAN. Method We screened clinical records of patients followed at 18 European consorted centres who were ≥18 years old at the onset of IgAV and received ≥1 rituximab dose. Furthermore, we identified patients with cIgAN (≥25% crescentic glomeruli and rapidly progressive glomerulonephritis), who were treated with rituximab. Remission was defined as Birmingham Vasculitis Activity Score (BVAS) <3 at month 6 after rituximab and renal response as stable or improved eGFR and ≥50% proteinuria reduction. Relapse was defined as an increase in BVAS requiring a change in immunosuppressive therapy. Outcomes of IgAV with severe nephritis (eGFR <60 mL/min) were compared with those of cIgAN. Results We included 61 patients with IgAV and 15 with cIgAN (Table). Rituximab was administered as initial therapy in 23/61 (38%) patients with IgAV and 13/15 with cIgAN (87%), while the remainder had refractory or relapsing disease. Active skin involvement was present in 49 patients (80%) and nephritis in 55 patients (90%) with IgAV at the time of starting rituximab. This was given alone in 13/61 (21%) or combined with GC in 48 (79%) patients with IgAV and in all those with cIgAN. Furthermore, cyclophosphamide was used in 15% of patients with IgAV and 40% of those with cIgAN. Remission at 6 months was achieved by 52 (85%) patients with IgAV and 12/13 (92%) of those treated with rituximab alone. A renal response was observed among 49/55 (89%) of those with nephritis. Patients with IgAV and severe nephritis had similar eGFR to those with cIgAN at the time of starting rituximab, but the latter had lower rate of remission and a higher frequency of kidney failure. A relapse occurred in 15/52 patients (29%) who achieved remission a median of 13 months (10-15) after rituximab. Eight patients resumed rituximab and achieved again remission. Conclusion Rituximab alone or in combination with GC and immunosuppressants appeared to achieve a high rate of remission in this cohort of adult-onset IgAV. Renal response among those with severe nephritis was also good, while this was worse among patients with cIgAN, suggesting substantial differences among these conditions despite similar histological appearances.

Rituximab treatment in resistant lupusnephritis: A single-center prospective study.

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) and failure to respond to traditional immunosuppression increases morbidity and mortality. Rituximab has been considered a novel therapeutic option for the management of SLE. We conducted a single-center, prospective, observational study from July 2018 to June 2019 to evaluate the effectiveness of rituximab in patients with resistant LN. Resistant LN was defined as the failure to respond to conventional immunosuppressive therapy including both cyclophosphamide and mycophenolate mofetil. All adult patients (>18 years) with biopsy-proven class III/IV LN were included in the study. Four doses of intravenous rituximab (375 mg/m2) on 0, 1, 2, 3 weeks were administered. Patients were followed for 6months, and the rates of complete renal response (CRR), partial renal response (PRR), or no renal response (NRR) were measured. The change in baseline 24-hour urine protein, mean serum creatinine levels, and mean serum CD-19 levels at 24 weeks were also measured. Six months after rituximab therapy, total sustained renal response (CRR+PRR) was observed in 52% cases of resistant LN (CRR was achieved in 24% of patients and PRR in 28%, respectively). Rituximab was associated with a significant decline in the 24-hour urine protein, even in non-responders. However, the improvement in eGFR and serum creatinine was not statistically significant. The mean absolute CD-19 count was significantly low in responders compared to the non-responder group. Rituximab is a safe and effective therapeutic strategy for patients with resistant LN.

Immunotherapy with genetically engineered T cells holds promise for the treatment of nonmalignant diseases in the dog.

The ability to genetically redirect the antigenic specificity of T cells using chimeric antigen receptors (CAR) has led to unprecedented durable clinical remissions in human patients with relapsed/refractory hematological malignancies. This remarkable advance in successful immune cell engineering has now led to investigations into the application of CAR-T-cell technology to treat nonmalignant diseases. The use of CAR-T cells to target and eliminate specific cell subsets involved in the pathogenesis of autoimmunity, fibrosis, senescence, and infectious disease represents a new direction for adoptive cell therapies. While the use of CAR-T cells for nonmalignant disease is still in its infancy, early reports of dramatic clinical responses to CAR-T cells targeting CD19+ B cells in patients with severe autoimmune disease raise the possibility that this approach could lead to durable remissions, eliminating the need for ongoing conventional immunosuppressive therapies. Excitingly, nonmalignant disease processes that may be addressed by CAR-T-cell therapy in humans also occur in our canine populations. Given that technologies for developing canine CAR constructs are now available, robust protocols have been described for generating canine CAR-T cells, and experience is being gathered with their clinical use in oncology, it is anticipated that CAR-T cells will soon enter the veterinary clinics for the treatment of debilitating nonmalignant diseases. Here, we provide a broad overview of CAR-T-cell therapies for nonmalignant diseases and extrapolate these advances into the veterinary space, highlighting areas in which canine CAR-T cells are poised to enter the clinics for the treatment of nonmalignant disease.

Exploring Advanced Therapies for Primary Biliary Cholangitis: Insights from the Gut Microbiota-Bile Acid-Immunity Network.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the effectiveness of conventional immunosuppressive therapy is disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and evidence is increasing that gut microbiota and bile acids play an important role in the pathogenesis of cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Autoimmune cholangitis has the potential to be improved through immune system modulation. Considering the failure of conventional immunotherapies and the involvement of gut microbiota and bile acids in the pathogenesis, targeting immune factors associated with them, such as bile acid receptors, microbial-derived molecules, and related specific immune cells, may offer breakthroughs. Understanding the gut microbiota-bile acid network and related immune dysfunctions in PBC provides a new perspective on therapeutic strategies. Therefore, we summarize the latest advances in research of gut microbiota and bile acids in PBC and, for the first time, explore the possibility of related immune factors as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Traditional Chinese medicine for idiopathic membranous nephropathy: A systematic review and meta-analysis

BackgroundIdiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative. ObjectiveThis study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN. MethodsThis study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website. ResultsThis study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29–1.46, I2 = 0%, P < 0.00001), complete remission (CR) rate (RR 1.78, 95% CI 1.48–2.15, I2 = 0, P < 0.00001), partial remission (PR) rate (RR 1.27, 95% CI 1.161.40, I2 = 0%, P < 0.00001), and serum albumin (ALB) levels (MD: 4.05, 95% CI: 3.02–5.09, I2 = 91%, P < 0.00001). TCM alone or in combination with Western medicine also reduced proteinuria levels (mean difference [MD]: 1.05, 95% CI: 1.30 to −0.79, I2 = 95%, P < 0.00001), serum creatinine (SCr) levels (MD: 7.47, 95% CI: 13.70 to −1.24, I2 = 97%, P = 0.02), and serum antibodies against M-type phospholipase A2 receptor levels (aPLA2Rab) (MD: 19.24, 95% CI: 33.56 to −4.93, I2 = 87%, P = 0.008). Moreover, the efficacy of combined TCM and Western medicine is superior to that of Western medicine alone in reducing the incidence of infection, hepatotoxicity, and thrombosis. Although the primary and secondary outcomes were consistent, the evidence was generally moderate. ConclusionThe results of this study suggest that TCM alone or in combination with Western medicine may be a feasible alternative therapeutic approach for the treatment of IMN. Nevertheless, additional, rigorously designed, high-quality, and extensive clinical trials are imperative to provide substantial evidence regarding the effectiveness of TCM in managing IMN.

Eculizumab as Additional Rescue Therapy in Myasthenic Crisis

Eculizumab is a monoclonal antibody blocking the terminal complement protein C5. As demonstrated in the phase III randomized, placebo-controlled, REGAIN clinical trial, eculizumab is efficacious in acetylcholine receptor antibody (AChR-Ab)-positive refractory generalized myasthenia gravis (gMG) (Myasthenia Gravis Foundation of America—MGFA class II–IV). It has not been studied in severe myasthenic exacerbation or myasthenic crisis (MGFA V). A 73-year-old man diagnosed with myasthenia gravis AChR-Ab positivity came to our observation for symptoms of bulbar and ocular weakness and unresponsiveness or intolerability to conventional immunosuppressive therapies (prednisone and azathioprine). Due to the recurrent clinical worsening with intubation over a short-term period, the patient was treated with eculizumab. After 15 days of eculizumab treatment, we observed a significant recovery of clinical condition. We discharged the patient to an outpatient regimen, where he is continuing with maintenance doses of eculizumab and slowly tapering steroid intake. The use of eculizumab in myasthenic crises is still anecdotal. Our case aims to provide eculizumab benefit for refractory severe gMG in a practical, real-world setting beyond the criteria of the REGAIN study. Further studies are needed to evaluate the efficacy and safety of eculizumab in myasthenic crises.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.

Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress.

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and pathology remain unclear, increasing evidence suggests that viral infection is a potential trigger of MDA5-DM. Multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5-DM. Distinctive skin rashes, rapidly progressive interstitial lung disease, peripheral lymphopenia and elevated serum ferritin levels are the most prominent clinical and laboratory features of MDA5-DM. Concomitant infection is a common complication of MDA5-DM. The proper evaluation of patients with MDA5-DM requires knowledge of the disease heterogeneity and clinical course variability. Several biomarkers, including serum levels of anti-MDA5 antibodies and biomarkers related to macrophage activation, have been identified as useful tools for monitoring disease activity and prognosis. MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis. Therefore, there is an urgent need to explore the key pathogenic mechanisms of MDA5-DM and develop novel therapeutic options for patients. This Review discusses recent clinical progress and pathogenic findings of MDA5-DM.

Features of immune mediated diseases in JAK2 (V617F)-positive myeloproliferative neoplasms and the potential therapeutic role of JAK inhibitors

ObjectiveThe Janus Kinase (JAK) 2 (V617F) mutation is the most frequently detected in myeloproliferative neoplasms (MPN). JAK2(V617F) mutation displays a pro-inflammatory phenotype that may be associated to a higher risk of immune mediated diseases (IMIDs), thromboembolic complications or other cancers. We aimed to evaluate the prevalence and main features of both rheumatic and non-rheumatic IMIDs in a cohort of MPNs patients with JAK2 (V617F) mutation. MethodsStudy of all patients diagnosed with MPNs and JAK2 (V617F) mutation at a tertiary hospital in Northern Spain from 2004 to 2022. We focused on patients with rheumatic IMIDs to assess the time from IMIDs diagnosis to the detection of JAK2V617F mutation, the clinical course and severity of the disease, potential thrombotic complications, malignancies and therapeutic response. Results130 patients (73 men/57 women; mean age, 70.1 ± 14.5 years) were identified. Fifty-four (41.5 %) patients were diagnosed with at least one IMID. The prevalence of rheumatic IMIDs was 7.7 % (n = 10), including rheumatoid arthritis (n = 4), polymyalgia rheumatica (n = 3), Sjögren syndrome (n = 1), antiphospholipid syndrome (n = 1) and autoinflammatory syndrome with WDR1 mutation (n = 1). Thrombotic complications were observed in 4 of these 10 patients. The clinical course of the rheumatic IMID was mild in most cases and responded to conventional immunosuppressive therapy. One patient was successfully treated with Baricitinib, a JAK1/JAK2 inhibitor. ConclusionsA high prevalence of rheumatic IMIDs is observed in patients with MPNs and JAK2 (V617F) mutation. JAK inhibitors might be a targeted therapy option in these patients.

Risk of Hepatitis B Virus Reactivation in Patients with Resolved Infection on Therapy with Corticosteroids and Conventional Synthesis Immunosuppressants for Kidney Disease: A Single-Center Analysis of 258 Patients.

The risk of hepatitis B virus reactivation in patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease has not been well described. We performed a retrospective study on the risk of hepatitis B virus reactivation in patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease between January 2012 and December 2021 in the Department of Nephrology at Ruijin Hospital. A total of 258 patients with a previously resolved hepatitis B virus infection [all treated with high-dose corticosteroids, of whom 192 were receiving corticosteroids combined with conventional synthesis immunosuppressant therapy, including cyclophosphamide (155), cyclosporine A (14), mycophenolate mofetil (14), and tacrolimus (9)] were enrolled. During a mean follow-up time of 21.66 months (range 9-70 months), hepatitis B virus reactivation was not observed in these patients. Among patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease, hepatitis B virus reactivation was not common and severe, suggesting that universal prophylaxis may not be justified or cost-effective in this clinical setting.

Treatment of Pediatric Pemphigus Foliaceus.

Pemphigus foliaceus (PF) is an autoimmune blistering disease limited to the superficial skin without mucosal involvement. It is clinically, histologically, and immunopathologically distinct from pemphigus vulgaris (PV). As data on pediatric PF is often merged with data on both pediatric and adult PV patients, isolating clinical outcomes in pediatric PF is not always possible. Therefore, the authors of this review analyzed clinical outcomes following therapy in pediatric PF patients only. A search of databases resulted in 33 pediatric patients with PF. In total, 19 (57.6%) patients were treated with conventional immunosuppressive therapies (CISTs), which consisted of systemic corticosteroids and multiple immunosuppressive agents (ISAs). Further, 14 (42.4%) patients were treated with biologic agents, predominantly rituximab (RTX). The mean age of those treated with biologics was 12.8 years (range = 0.88-18 years) compared to 8.9 years (range = 0.92-15 years) of those treated with CIST (p = 0.01). Treatment with biologics was initiated significantly longer after the diagnosis of PF when compared to patients treated with CIST (p = 0.003). RTX was used in all patients who received biologic therapy. Two (6%) patients also received intravenous immunoglobulin. When clinical outcomes were compared between CIST and biologic therapy, rates of clinical remission, partial remission, and relapse, were not statistically significantly different between groups. When RTX was used, rates of relapse and adverse events were higher in those treated with the lymphoma protocol (375 mg/m2once weekly for four weeks) compared to those treated with the rheumatoid arthritis protocol (two doses of 1,000 mg two weeks apart) (p < 0.0001). The incidence of adverse events was statistically significantly higher in patients treated with CIST when compared to RTX (p = 0.003). These included both physical and psychological changes. The infection rate after treatment with RTX was 7.1%. These outcomes occurred during a follow-up of 12.5 months (range = 1-36 months) in the CIST group and 20.5 months (range = 6-67 months) in the biologic therapy group. The difference in the follow-up period was not statistically significant. The literature suggests that biologics are superior to CIST in treating pemphigus patients.The results of this review suggest similar responses to therapy in pediatric PF patients treated with biologics compared to CIST. This may have been due to a limited duration of follow-up and a lack of detailed treatment outcomes in pediatric PF patients. The data in this review strongly suggests that specific treatment protocols need to be developed and implemented for pediatric PF patients. These patients are at a critical phase in life where PF therapy can influence or affect physical growth, hormonal changes, psychosocial development, and essential education.

New Therapeutic Approaches to Large-Vessel Vasculitis.

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are large-vessel vasculitides affecting the aorta and its branches. Arterial damage from these diseases may result in ischemic complications, aneurysms, and dissections. Despite their similarities, the management of GCA and TAK differs. Glucocorticoids are used frequently but relapses are common, and glucocorticoid toxicity contributes to significant morbidity. Conventional immunosuppressive therapies can be beneficial in TAK, though their role in the management of GCA remains unclear. Tumor necrosis factor inhibitors improve remission rates and appear to limit vascular damage in TAK; these agents are not beneficial in GCA. Tocilizumab is the first biologic glucocorticoid-sparing agent approved for use in GCA and also appears to be effective in TAK. A better understanding of the pathogenesis of both conditions and the availability of targeted therapies hold much promise for future management.

Clinical outcomes following cessation of parenteral immunoglobulin therapy following lung transplantation

Broad use of parenteral immunoglobulin (IgG) therapy in lung transplant (LTx) patients occurs without robust clinical evidence or guidelines. Main indications include secondary hypogammaglobulinemia, antibody-mediated rejection (AMR), and treatment or prevention of graft rejection where the use of conventional immunosuppressive therapies is contraindicated. As part of routine auditing of IgG use in our LTx service, we assessed for adverse clinical outcomes related to IgG therapy cessation between November 2017 and February 2022. Of 220 LTx recipients receiving IgG therapy at our center during this period (approximately 20% of our total LTx cohort), 48 patients ceased therapy. No adverse outcomes were experienced in 83.3% patients. About 10.4% recommenced therapy for the same indication within 6months with no longer term sequelae. One AMR patient developed progressive Chronic lung allograft dysfunction and died within 12months, where therapy cessation was patient-initiated and associated with general noncompliance. These data provide reassurance that physician-directed cessation of IgG therapy is safe when based on sound clinical information and part of a robust clinical auditing process.

Systemic sclerosis associated myopathy: how to treat.

Systemic sclerosis (SSc) and myositis are two different entities that may coexist as an overlap syndrome. Immunological biomarkers such as anti-PM/Scl or anti-Ku reinforce the syndrome. This review is focused on the treatment of different and characteristic manifestations of this syndrome. Among the different phenotypes of muscle involvement in patients with SSc, the fibrotic pattern and the sporadic inclusion body myositis must be identified early to avoid a futile immunosuppressive treatment. Other forms such as dermatomyositis, non-specific myositis and immune-mediated necrotizing myopathy need to receive conventional immunosuppressive therapy considering that high dose of glucocorticoids may induce a scleroderma renal crisis in patients with SSc. Physicians must be aware of the existence of a "double trouble" association of hereditary myopathy with an autoimmune phenomenon. Several autoantibodies, mainly anti-PM/Scl and anti-Ku may help to define specific phenotypes with characteristic clinical manifestations that need a more specific therapy. Vasculopathy is one of the underlying mechanisms that link SSc and myositis. Recent advances in this topic are reviewed. Current treatment of SSc associated myopathy must be tailored to specific organs involved. Identifying the specific clinical, pathological, and immunological phenotypes may help to take the correct therapeutic decisions.

Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE), the prototype of systemic autoimmune diseases is characterized by extreme heterogeneity with a variable clinical course. Renal involvement may be observed and affects the outcome. Hydroxychloroquine should be administered to every lupus patient irrespective of organ involvement. Conventional immunosuppressive therapy includes corticosteroids, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine, cyclosporine and tacrolimus. However, despite conventional immunosuppressive treatment, flares occur and broad immunosuppression is accompanied by multiple side effects. Flare occurrence, target organ involvement, side effects of broad immunosuppression and increased knowledge of the pathogenetic mechanisms involved in SLE pathogenesis as well as the availability of biologic agents has led to the application of biologic agents in SLE management. Biologic agents targeting various pathogenetic paths have been applied. B cell targeting agents have been used successfully. Belimumab, a B cell targeting agent, has been approved for the treatment of SLE. Rituximab, an anti-CD20 targeting agent is also used in SLE. Anifrolumab, an interferon I receptor-targeting agent has beneficial effects on SLE. In conclusion, biologic treatment is applied in SLE and should be further evaluated with the aim of a good treatment response and a significant improvement in quality of life.

A new approach to immunosuppressive therapy in patients with glomerulonephritis with nephrotic syndrome

Glomerulonephritis (GN) is a group of immuno-inflammatory kidney diseases with predominant glomerular lesions that are difficult to treat. The greatest problems are caused by the treatment of GN with nephrotic syndrome, which often has a recurrent course. The aim of the research was to study the effectiveness of recombinant interleukin-2 (rIL-2) therapy in the GN patients with nephrotic syndrome. 62 patients with a nephrotic form of primary GN with frequent relapses admitted to the Nephrology Department have been recruited into the study. The age of patients was from 18 to 65 years. The patients underwent standard examinations, as well as immunological studies, before administration of the anti-relapse treatment, and 12 months after the treatment was started. Immunological testing included immunophenotyping of lymphocytes with counting of T and B lymphocytes, immunoregulatory and activated subpopulations of T lymphocytes, determination of urinary immunoglobulins (IgM, IgG, IgA) by immunoturbidimetric assays, proinflammatory cytokines – IL-1β, IL-8, IL-17A and anti-inflammatory cytokine IL-10 by ELISA tests. As a result of studies, the examined patients showed an increased contents of T helper cells, activated T lymphocytes (CD8+HLA-DR+CD45+, CD3+CD8brightCD38+) along with decreased numbers of Treg cells and an increased contents of proinflammatory cytokines IL-1β, IL-8, IL-17A and immunoglobulins of all three classes in urinary samples.The cohort of patients with GN selected for the study was divided in two groups (the main group and the comparison group). In addition to nephroprotective and steroid therapy, the treatment regimen of patients included rIL-2 in the main group, or cyclophosphamide in the comparison group. Regardless of the method used, the levels of protein, IgG and IL-17A in the urine proved to be decreased relative to the initial values; the contents of B cells and HLA-DR+ cytotoxic T lymphocytes in peripheral blood were found to be decreased. The revealed changes were more pronounced in the main group of patients. By 12 months after starting the treatment, the mentioned indexes began to differ significantly in the main group from those in the comparison group. Serum creatinine levels, numbers of T helper cells and Treg cells, IL-1β levels in urine did not undergo significant changes in the comparison group, whereas a decrease in serum creatinine and urinary IL-1β was registered in the main group of patients, along with decreased number of T helpers and increased numbers of Treg cells. In the main group of patients treated with rIL-2, the average number of relapses per year decreased by 4 times, showing only a 1.2-fold decrease in the comparison group. Hence, the low-dose therapy with rIL-2 may be considered an effective and safe alternative to conventional immunosuppressive therapy and a new option of the targeted treatment of glomerulonephritis with frequent recurrence of nephrotic syndrome.

Predictive Factors of a New Episode of Suppuration after Remission of Fistulizing Ano Perineal Crohn's Disease: A Moroccan Series

Fistulizing ano-perineal lesions occur in more than 20% of patients with Crohn's disease (CD). Although many medical and surgical treatments are now available, the relapse rate of such lesions remains high at nearly 30%. The objective of this study was to identify factors predictive of a new episode of anal suppuration in patients with fistulizing ano-perineal CD initially put into remission. This was a retrospective single-center study that included between 2018 and 2022 all patients with CD complicated by ano-perineal fistula put into remission. Achievement of remission was defined by the absence of new suppuration within 3 months of the last drainage surgery. Fifty-seven patients (57% female; median age at drainage 31 years) with multiple episodes of suppuration were included consecutively during the period. The rate of new ano-perineal suppuration was 22%, which occurred within a median of 1.8 years. Actuarially, survival without new suppuration was 96.7% at 1 year, 78.4% at 3 years, and 74.4% at 5 years. In the 38 (66.6%) patients receiving anti-TNF therapy after drainage, colonic (OR 1.25, p = 0.015) or ileocolic (OR 5.16, p = 0.015) location of CD, stenosing luminal phenotype (OR 5. 32, p = 0.013) and discontinuation of anti-TNF therapy during follow-up (OR 3.37, p = 0.049) were associated with an increased risk of a new suppurative episode in multivariate analysis. Conversely, discontinuation of conventional immunosuppressive therapy was associated with a reduced risk of a new episode of suppuration (OR 0.22, p = 0.29).

Efficacy and safety of rituximab for primary membranous nephropathy with different clinical presentations: a retrospective study.

Rituximab (RTX) is gaining increasing clinical acceptance in the treatment of primary membranous nephropathy (PMN), with demonstrated efficacy and safety. However, there are few clinical studies on RTX for PMN in Asian populations, especially in China. To observe and analyse the efficacy and safety of RTX treatment, 81 patients with PMN suffering from nephrotic syndrome (NS) were enrolled and divided into an initial therapy group, a conventional immunosuppressive therapy relapse group, and a conventional immunosuppressive therapy ineffective group according to their pre-RTX treatment background. Patients in each group were followed up for 12 months. The primary outcome was clinical remission at 12 months, and the secondary outcomes were safety and the occurrence of adverse events. At 12 months, 65 of 81 (80.2%) patients achieved complete (n=21, 25.9%) or partial (n=44, 54.3%) remission after rituximab treatment. Thirty-two of 36 (88.9%) patients in the initial therapy group, 11 of 12 (91.7%) patients in the relapse group and 22 of 33 (66.7%) patients in the ineffective group achieved clinical remission. All 59 patients with positive anti-PLA2R antibodies showed a decreasing trend in antibody levels after RTX treatment, and 55 (93.2%) of them achieved antibody clearance (<20 U/mL). Logistic regression analysis showed that a high anti-PLA2R antibody titer (OR=0.993, P=0.032) was an independent risk factor for nonremission. Adverse events occurred in 18 (22.2%) patients, of which 5 (6.2%) were serious adverse events, and none were malignant or otherwise fatal. RTX alone can effectively induce remission PMN and maintain stable renal function. It is recommended as the first choice of treatment and is also effective in patients who relapse and have poor responses to conventional immunosuppressive therapy. Anti-PLA2R antibodies can be used as a marker for RTX treatment monitoring, and antibody clearance is necessary to achieve and improve the rates of clinical remission.

The Clinical Outcome in AChR-Positive Generalized Myasthenia Gravis: A Retrospective Observational Study.

Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, and in over 80% of cases, antibodies are identified against the nicotinic type of acetylcholine receptor (AChR) on the muscle endplate. Despite the availability of various treatment options, patients with MG experience relapses and remission during the course of the disease. Aims and Objective: To understand the clinical profile, predictors of outcomes in acetyl choline receptor (AChR) antibody positive generalized MG. This is a retrospective, single-centre, observational study of 108 patients with AChR positive generalized MG. We collected data on clinical and demographical profiles, treatments received, and treatment responses from those who fulfilled inclusion criteria over a mean follow up period of 33.75 ±7.30 months. Clinical outcomes were studied in terms of the type of remission and crisis or disease exacerbations patients had, considering different variables and treatment received. We found the commonest initial symptoms were ocular or oculo-bulbar, which progressed to generalized MG in the first year of disease onset. 36 (33.3%) patients experienced a crisis requiring mechanical ventilation within a mean period of 9.4 ±4.77 months from the disease onset. Multivariate regression analysis showed late-onset MG (age of onset between 50-70 years) and treatment with rituximab were better correlated with remission, (odd ratio of 4.7; 95 % CI ,1.12 -12.6; P value < 0.05 and odd ratio of 4.56; 95 % CI ,1.2 -10.04; P value < 0.05) respectively. While treatment with Mycofenolate Mofetile (MMF) was associated with a higher number of relapses (odd ratio of 1.8; 95 % CI ,0.08 -0.96; P value < 0.05). Treatment with Rituximab showed a higher rate of remission as compared to treatment refractory (TR) on conventional immunosuppressant therapy (IST). Out of 35(32 %) thymoma patients, 21 patients underwent thymectomy and these patients showed significantly greater rate of remission as compared both thymoma patients who denied thymectomy as a treatment option (N = 10 ;55.60 % vs N = 4; 23.50%). In this study of AChR antibody positive generalized MG patients, we found that nearly one-third of them experienced myasthenic crisis despite receiving the best medical care. Rituximab appeared to be effective in the treatment of refractory MG and those who failed thymectomy. Thymectomy was associated with better outcomes in patients, both with or without a thymoma.

Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review

Systemic sclerosis (SSc) is an autoimmune, multi-organ, connective tissue disease associated with significant morbidity and mortality. Conventional immunosuppressive therapies demonstrate limited efficacy. Autologous hematopoietic stem cell transplantation (HCT) is more efficacious but carries associated risks, including treatment-related mortality. Here, we review HCT as a treatment for SSc, its efficacy and toxicity in comparison to conventional therapies, and the proposed mechanisms of action. Furthermore, we discuss the importance of and recent developments in patient selection. Finally, we highlight the knowledge gaps and future work required to further improve patient outcomes.