Combined Immunosuppressive Therapy Research Articles

Comment on: Combination of immunosuppressive therapy and nintedanib improves capillaroscopic changes in systemic sclerosis-interstitial lung disease: a case report.

Comment on: Combination of immunosuppressive therapy and nintedanib improves capillaroscopic changes in systemic sclerosis-interstitial lung disease: a case report.

Comment on: Combination of immunosuppressive therapy and nintedanib improves capillaroscopic changes in systemic sclerosis-interstitial lung disease: a case report. Reply

Comment on: Combination of immunosuppressive therapy and nintedanib improves capillaroscopic changes in systemic sclerosis-interstitial lung disease: a case report. Reply

Combination of immunosuppressive therapy and nintedanib improves capillaroscopic changes in systemic sclerosis-interstitial lung disease: a case report.

Combination of immunosuppressive therapy and nintedanib improves capillaroscopic changes in systemic sclerosis-interstitial lung disease: a case report.

Development of severe aplastic anemia during steroid therapy for autoimmune hemolytic anemia

A 50-year-old male patient was admitted for close monitoring of anemia (hemoglobin level, 5.0 g/dl). Autoimmune hemolytic anemia (AIHA) of warm type was diagnosed based on the elevated reticulocyte and bone marrow erythroblast counts, elevated indirect bilirubin level, serum haptoglobin level below the detection limit, and positive direct Coombs test result. The patient responded to prednisolone 60 mg/day (1.0 mg/kg); however, pancytopenia was observed during gradual dose tapering and maintenance therapy. The bone marrow showed remarkable hypoplastic findings, and magnetic resonance imaging scans of the thoracolumbar spinal cord showed an overgrowth of the adipose tissue. Thus, the patient was diagnosed with aplastic anemia (AA) stage 4. He was successfully treated with a combination of immunosuppressive therapy (anti-thymocyte globulin +cyclosporine), which allowed him to reduce his dependence on transfusions. However, the direct Coombs test result remained positive even after hematopoietic recovery. Aplastic anemia following AIHA treatment is extremely rare and has not been reported previously.

COVID-19 in pediatric nephrology centers in Turkey.

There is limited data on COVID-19 disease in children with kidney disease. We aimed to investigate the characteristics and prognosis of COVID-19 in pediatric nephrology patients in Turkey. This was a national, multicenter, retrospective cohort study based on an online survey evaluating the data between 11th March 2020 and 11th March 2021 as an initial step of a detailed pediatric nephrology COVID-19 registry. Two hundred and three patients (89 girls and 114 boys) were diagnosed with COVID-19. One-third of these patients (36.9%) were between 10-15 years old. Half of the patients were on kidney replacement therapy: kidney transplant (KTx) recipients (n = 56, 27.5%), patients receiving chronic hemodialysis (n = 33, 16.3%) and those on peritoneal dialysis (PD) (n = 18, 8.9%). Fifty-four (26.6%) children were asymptomatic. Eighty-two (40.3%) patients were hospitalized and 23 (28%) needed intensive care unit admission. Fifty-five percent of the patients were not treated, while the remaining was given favipiravir (20.7%), steroid (16.3%), and hydroxychloroquine (11.3%). Acute kidney injury developed in 19.5% of hospitalized patients. Five (2.4%) had MIS-C. Eighty-three percent of the patients were discharged without any apparent sequelae, while 7 (3.4%) died. One hundred and eight health care staff were infected during the study period. COVID-19 was most commonly seen in patients who underwent KTx and received HD. The combined immunosuppressive therapy and frequent exposure to the hospital setting may increase these patients' susceptibility. Staff infections before vaccination era were alarming, various precautions should be taken for infection control, particularly optimal vaccination coverage.

БОЛЕЗНЬ МИНИМАЛЬНЫХ ИЗМЕНЕНИЙ В ТЕРАПЕВТИЧЕСКОЙ ПРАКТИКЕ

The disease of minimal changes occurs in 10–15% of adult patients with idiopathic nephrotic syndrome, it often has a relapsing course. Glucocorticoids are effective in achieving remission, but in some patients steroid resistance and progressive course of the disease are observed. Recent studies have investigated the mechanismsof minimal change disease development for the purpose of estimating the prognosis of the disease and the efficacy of immunosuppressive therapy. Aim. The aim of the present study was to review current data on the diagnosis, pathogenetic therapy of minimal change disease, and to demonstrate the clinical case of a relapsed disease in steroid resistant patient. Material and methods. A review of original research in the foreign and domestic literature on the subject over the past 5 years was conducted. Results and discussion. Minimal change disease is clinically manifested by rapid, almost sudden development of nephrotic syndrome (proteinuria, hypoalbuminemia, marked hypercholesterolemia, and massive generalized edema). Arterial hypertension and microhematuria occur occasionally. Glucocorticoids are being prescribed to achieve early remission even before morphological verification of the diagnosis. The course of the disease is mostly benign. The majority of patients with steroid sensitivity have long-term preserved renal function, while steroid resistance is associated with a progressive course leading to terminal renal failure. The presented clinical case is interesting because the unfolded picture of the disease of minimal changes including severe nephrotic syndrome and steroid-resistance, appeared in the patient a year after the disease debut. After receiving combined immunosuppressive therapy for 16 weeks incomplete remission was achieved. Conclusion. Unfortunately, at present, there are no available reliable methods to predict the development of steroid resistance and there are no effective therapies guaranteeing the achievement of remission in such cases.

Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.

Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients.

This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological transformation in Chinese patients. 104 SLE patients with biopsy-proven LN class II were included and divided into proteinuria group (proteinuria ≥ 0.4g/24h, with or without microscopic hematuria) and hematuria group (microscopic hematuria with proteinuria < 0.4g/24h).Patients were treated with glucocorticoid alone (GC monotherapy) or GC in combination with other immunosuppressant (combination therapy). The rates of remission, relapse, histological transformation, end-stage renal disease (ESRD), adverse events, and risk factors related to the outcomes were analyzed. During the median follow-up of 77.5 (IQR 58-116.5) months, all the 104 patients achieved remission. Relapse occurred in 69 cases (66.3%), of which 37 were of renal relapse (35.6%). Histological transformation was found in 14 of the 16 (87.5%) cases who received repeated renal biopsy after renal relapse. At the end of follow-up, 3 (2.9%) patients developed ESRD. There were no significant differences in the rates of relapse, histological transformation, adverse events and in the time from remission to relapse between the proteinuria group and the hematuria group. In contrast, the cumulative relapse rate in the GC monotherapy group was much higher than that in the combination group (P < 0.01). Adverse events occurred in 55 (57.3%) patients during follow-up. Patients with LN class II have high rates of relapse and renal histological transformation and need optimal maintenance therapy. • The rates of relapse and histological transformation are high in patients with LN class II. • Patients with LN class II are suggested to receive combination therapy and consider repeat renal biopsy after renal relapse.

Effectiveness of immunosuppressive therapy for lymphocytic myocarditis according: data from actual clinical practice

Aim. To compare the effectiveness of standard heart failure therapy with and without combined immunosuppressive therapy in patients with documented lymphocytic myocarditis (LM) based on data from actual clinical practice.Material and methods. This observational study included 70 patients with documented LM, 40% (n=28) of whom received immunosuppressive therapy. All patients underwent standard echocardiographic and laboratory investigations, endomyocardial biopsy with histological, immunohistochemical and molecular genetic analysis. Contrast-enhanced cardiac magnetic resonance imaging was performed in 74% of patients. All patients received standard therapy for heart failure at baseline.Results. The groups did not differ in demographic and echocardiographic characteristics. The appointment of immunosuppressive therapy was accompanied by an increase in ejection fraction by 12,2% compared to 6,4% (p=0,02). There were no significant differences in combined endpoints (survival and the need for heart transplantation) depending on therapy regimen (log-rank p=0,97).Conclusion. The prognosis of patients with chronic LM depends on the process activity, the severity of impaired hemodynamics and ventricular arrhythmias, as well as on the presence of persistent viral infection. Compliance with patient selection algorithm before prescribing immunosuppressive therapy is associated with the improvement in myocardial global contractility.

The Risk Factors of Exacerbation in Interstitial Pneumonia With Autoimmune Features: A Single-Center Observational Cohort Study.

ObjectivesTo investigate the long-term outcomes, including risk factors, for exacerbation between monotherapy and combination therapy in patients with interstitial pneumonia with autoimmune features (IPAF).MethodsWe assessed 672 patients between April 2009 and March 2019 who were evaluated using high-resolution computed tomography (HRCT) of the chest. We applied the IPAF criteria. Fifty-two patients who visited our department for at least 6 months were diagnosed with IPAF. Clinical, laboratory, and imaging data were collected from medical records and statistically analyzed.ResultsAmong the 52 cases of IPAF, we compared the characteristics at diagnosis between treated (n = 28) and untreated patients (n = 24). The exacerbation rates were 42.9% (n = 12) and 8.3% (n = 2) (P = 0.0051), respectively. Among the treated patients, smoking history, high titer of KL-6, and the duration from diagnosis to the start of treatment were significant risk factors for exacerbation (P = 0.0062, 0.011, and 0.019, respectively). The number of risk factors was significantly and positively associated with exacerbation rate (P = 0.0053). Among the treated patients, glucocorticoid (GC) monotherapy was used in 13 cases, and GC and immunosuppressant (IS) combination therapy was used in 14 patients. There was no significant difference in the treatment methods between patients with and without risk factors (P = 0.47). When comparing the long-term outcomes between the monotherapy and combination therapy groups, the 3-year non-exacerbation rates were 72.9 and 45.9% (P = 0.020), respectively.ConclusionsIPAF patients with risk factors had a high exacerbation rate, regardless of the type of treatment. New interventions aimed at preventing exacerbations in these patients are required.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00371-3.

Development of Exogenous Insulin Antibody Syndrome in a Patient with Newly Diagnosed Type1 Diabetes Successfully Treated with Oral Immunosuppressive Monotherapy.

Exogenous insulin antibody syndrome (EIAS), which rarely occurs in the patient with type 1 diabetes, results in antibody-induced insulin resistance, hyperglycemia, ketosis, ketoacidosis, and hypoglycemia when insulin is released from the saturated insulin antibodies. Recommended treatment regimens include glucocorticoids, immunosuppressants, and plasmapheresis. In the patient with type 1 diabetes, glucocorticoids may by inducing and/or worsening ketoacidosis be contraindicated. With immunosuppressants, various anecdotal treatment regimens have been reported. Currently the most commonly recommended regimen is intravenous immunosuppressive therapy in combination with oral immunosuppressants. Herein we describe a patient in whom oral immunosuppressant monotherapy with mycophenolate resulted in the cure of EIAS, thus avoiding the expense associated with intravenous immunosuppressant therapy and/or hospitalization for plasmapheresis.

Safety and efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with systemic lupus erythematosus

Objective: to study the safety and efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).Patients and methods. The study included 75 patients with definite diagnosis of SLE at the age of 19–68 years, 10 (13%) of them had high SLE activity, 18 (24%) – moderate, 42 (56%) – low, in 5 (7%) patients the disease was in remission. PPV-23 was injected subcutaneously in a single dose of 0.5 ml. In 60 patients the follow-up period was ≥12 months, in 15 – from 2 to 6 months. Patients were examined before and 1, 3 and 12 months after immunization.Results and discussion. In 38 (50.7%) patients, standard local vaccination reactions of mild and moderate severity were noted, in 1 (1.3%) – a general reaction of mild severity, in 2 (2.7%) – mild diarrhea during 1 day, in 1 (1.3%) – a hyperergic reaction of the Artyus phenomenon type, the symptoms were relieved within 7 days. During 12 months of follow-up, neither exacerbations of SLE, reliably associated with vaccination, nor new autoimmune phenomena, were detected. After 1 year of observation, the number of responders to vaccination was 58%, non-responders – 42%. The duration and activity of the disease, age over 50 years, glucocorticoid therapy &gt; 10 mg per day, did not significantly affect the vaccine response. There was a decrease in the immune response in patients on biologic DMARDs (bDMARDs) therapy compared to patients without such treatment (43 and 68% of cases, respectively), p=0.058. There was no difference between rituximab and belimumab treated subjects. There was a tendency for the prevalence of vaccination responses among patients, who received bDMARDs &lt;1 year before immunization, as well as among patients in whom this therapy was initiated after the administration of PPV-23. There was a positive trend in decrease of pneumonia, acute and exacerbations of chronic bronchitis episodes and sinusitis.Conclusion. Sufficient immunogenicity, good tolerability and clinical efficacy of PPV-23 in patients with SLE, including those who received combined immunosuppressive therapy, have been shown. The use of bDMARDs reduces the number of patients with a vaccine response. The number of responders to vaccination increases when immunization is carried out before the initiation of therapy with bDMARDs or when this therapy is initiated &lt;1 year before immunization. Further long-term prospective studies in large patient cohorts are required.

P297 HLA-DQA1*05 allele and its association with the secondary loss of response to infliximab in patients with Inflammatory Bowel Disease

Abstract Background It is estimated that around 40-50% of patients with Inflamatory Bowel Disease (IBD) will experience a secondary loss of response (SLR) to infliximab, being the immunogenicity a fundamental mechanism. The HLA class II allele, DQA1*05, that codifies the adaptative immune response, is present in approximately 40% of patients treated with anti-TNF, and has been recently associated with a higher probability of immunogenicity, secondary loss of response and discontinuation of anti-TNF therapy. The aim of this study was to evaluate if the presence of one o more copies of this allele is associated with a higher chance of SLR in patients with IBD treated with infliximab in our project study area. Methods Retrospective observational cohort study. We conducted a review of our unit’s database, including in the study patients with IDB treated with infliximab that responded to the induction, in which the presence of HLA-DQA1*05 had been tested. SLR was defined as the recurrence or worsening of symptoms that entailed a treatment change or intensification, hospitalization or surgery. The predictive factors for SLR were identified through a uni and multivariate Cox regression analysis. Results 88 patients with IDB were included (63 with Crohn’s Disease and 25 with Ulcerative Colitis), followed up to the SLR (52,3%) or a median of 35 months (IQR=58). 42% of these patients were carriers of the HLA-DQA1*05 allele. Patients’ clinical features are gathered in table 1. In the univariate analysis the disease duration in years (HR=0,9, IC 95% 0,85-0,97, p=0,008) and the presence of HLA-DQA1*05 (HR=2,27, IC 95% 1,07-4.83, P=0,03) were associated with the SLR. In the multivariate analysis, adjusted for smoking, previous restrictive surgery, years of evolution of the disease and the presence of combined immunosuppressive therapy, only the presence of HLA-DQA1*05 remained associated to the SLR (HR=2,32, IC 95% 1,07-5,02, p=0,03). Figure 1. Conclusion The presence of the HLA-DQA1*05 allele is frequent in patients with IBD, and it is associated with a secondary loss of response to infliximab. If confirmed with prospectively designed studies, the determination of this allele could guide physicians on the therapeutic decision making, advancing towards a more accurate medicine.

Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD.

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.

OP0286 CHARACTERISTICS ASSOCIATED WITH SEVERE COVID-19 OUTCOMES IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): RESULTS FROM THE COVID-19 GLOBAL RHEUMATOLOGY ALLIANCE (COVID-19 GRA)

OP0286 CHARACTERISTICS ASSOCIATED WITH SEVERE COVID-19 OUTCOMES IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): RESULTS FROM THE COVID-19 GLOBAL RHEUMATOLOGY ALLIANCE (COVID-19 GRA)

AB0411 CHALLENGES IN THE MANAGEMENT OF MIXED CONNECTIVE TISSUE DISEASE: A RETROSPECTIVE ANALYSIS OF THE MCTD COHORT IN A TERTIARY REFERRAL CENTRE

Background:As a rare, complex, and heterogeneous disease, mixed connective tissue disease (MCTD) represents a challenge for clinical practice.Objectives:We aimed to unravel potential pitfalls including correct referral diagnosis, fulfilment of diagnostic criteria, distinction from other CTDs, disease course and activity, and treatment modalities.Methods:We analysed the prospectively collected MCTD cohort at our tertiary referral centre. The patients’ medical histories were investigated for fulfilment of Sharp’s (1), Kasukawa’s (2), and Alarcón-Segovia’s (3) diagnostic MCTD criteria. We defined overlap syndromes as simultaneous fulfilment of clinical as well as immunological criteria of two defined rheumatic diseases. Disease conversion was defined as emergence of new symptoms and autoantibodies consistent with another rheumatic disease. Remission was defined by simultaneous systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trial and research (EUSTAR) activity index &lt;2.5. Disease phenotype and disease activity were monitored over time and all patients were evaluated for fulfilment of classification criteria of various connective tissue diseases.Results:Out of 85 patients initially referred as MCTD, only one third fulfilled the diagnostic MCTD criteria. Most of the remaining patients had undifferentiated CTD (29%) or overlap syndromes (20%). In our final cohort of 33 MCTD patients, 6 (48%) also met the classification criteria of systemic sclerosis, 13 (39%) those of systemic lupus erythematosus (SLE), 6 (18%) those of rheumatoid arthritis, and 3 (9%) those of primary myositis. Over the median observation period of 4.6 (1.6, 9.9) years, only two patients (6%) underwent disease conversion from MCTD to SLE and no patient converted towards other diseases. The number of patients in remission increased from 6 (18%) to 15 (45%) due to introduction of immune modulatory treatment. Combination therapy was favoured in most cases (17 patients, 52%), whereas monotherapy was less frequent (12 patients, 36%), and only 4 (12%) patients remained without immune modulators until the end of the follow-up period. Hydroxychloroquine, prednisone, and methotrexate were the most frequently used medications in our cohort.Conclusion:Our study showed a high risk for misdiagnosis for patients with MCTD. Phenotype conversion was a very rare event. As a multi-organ disease, MCTD required prolonged (combined) immunosuppressive therapy to achieve remission. The establishment of an international registry with longitudinal data from observational multi-centre cohorts might represent a first step to address the many unmet needs of MCTD.

Management of Myositis-Associated Interstitial Lung Disease.

Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies’ status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.

Role of Memory B Cells in Antibody Mediated Rejection: A Proof of Concept

<h3>Introduction</h3> Antibody mediated rejection (AMR) diagnosis, monitoring and treatment is exclusively based on circulating donor specific antibodies (DSA). However, DSA often fails to predict and diagnose AMR, since it does not represent the whole HLA-specific memory B cell (mBc) repertoire. Central and peripheral donor (HLA)-sp B-cell responses may offer a new diagnostic and therapeutic target. <h3>Case Report</h3> 44 years old female affected from an advanced Chagasic cardiomyopathy refractory to therapy was listed for heart transplant with a PRA of 67% in 03/2019. She was transplanted in 11/2019, with a negative CDC-XM. Induction was based on basiliximab and tacrolimus-based triple therapy with Mycophenolate mofetil and steroids. Despite a negative CDC-XM, 5 C3q-fixing DSA were detected (A3, DR1, DR7, DPB1, DQ2 and DQ5). Post-op was uneventful and biventricular function was preserved at day 7. The 14-day endomyocardial biopsy showed acute cellular rejection G2R and p(AMR)1 i+ with persistent DSAs. High doses of esteroids, IVIG and plasmapheresis were started. The SAB assay on day 25 showed persistent detection of all DSA, although with lower MFI levels. To characterize B-cell immune response, we used a novel HLA-specific B-cell FluorSpot assay. Bone marrow aspirate and peripheral blood demonstrated high frequencies of donor(HLA)-sp IgG-producing plasma cells and circulating donor-specific mBc, respectively, against different donor(HLA)-Ag specificities <b>(figure 1)</b>. Given patient's favorable evolution, with two main immune compartments showing anti-donor B-cell activation requiring a combined immunosuppressive therapy, no additional treatment was started. At 12 months of follow-up the patient remains clinically stable with negative ACR/pAMR EMB. <h3>Summary</h3> Our data highlights the need of a more accurate evaluation of the anti-donor humoral immune response leading to DSA production in order to refine current immune-risk stratification and ultimately help decision-making regarding the type of rescue immunosuppressive therapy.

“Triple-positive” renal limited vasculitis presenting with rapidly progressive glomerulonephritis

Rationale: Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) in a case of glomerulonephritis is often identified as a “double-positive” disease. Interestingly, the majority of “double positive” ANCA is myeloperoxidase (MPO)-ANCA and some of the MPO-ANCA positive cases showed intrarenal arteritis, suggesting an ANCA-associated kidney lesion. Proteinase 3-ANCA positive diseases are also rarely reported. Patients positive for all three antibodies, i.e., triple-positive patients, are extremely rare. Patient's Concern: A 53 year-old female presented with anasarca and oliguria of 2 months’ duration. Diagnosis: Pauci-immune type renal limited crescentic glomerulonephritis positive for MPO-ANCA, proteinase 3-ANCA, and anti-GBM antibody (triple-positive). Interventions: Intravenous high dose cyclophosphamide, oral azathioprine, intravenous methylprednisolone, and plasma exchange as per British Health Professionals in Rheumatology Guidelines. Outcomes: After one-month follow-up, anasarca and proteinuria were lessened, serum creatinine was normalized, titers of MPO-ANCA levels were decreased, and anti-GBM antibody levels were normalized. Lessons: Triple-positive renal limited vasculitis is rare and response to combined immunosuppressive therapy and plasma exchange can contribute to successful remission.

Effect of immunosuppressive therapy in inflammatory cardiomyopathy: data from The Czech Inflammatory Cardiomyopathy Immunosuppressive Trial.

The indications for specific treatment in the cases of inflammatory cardiomyopathy are based on limited data from several small clinical trials. A comparison of the effect of two dose regimens of combined immunosuppressive therapy by adding them to conventional heart failure therapy and comparing them with conventional heart failure therapy alone in patients with inflammatory cardiomyopathy. We enrolled 20 patients; mean age 46.10±7.33 years, duration of symptoms <6 months, LVEF ≤40 %, NYHA class II-IV, with biopsy‑proven myocarditis. Patients were randomly separated into groups treated with immunosuppressive therapy in addition to conventional heart failure therapy or to a group treated with conventional heart failure therapy alone. Clinical and echocardiographic parameters were evaluated. The baseline values of LVEF in the group of immunosuppressive therapy (LVEF 22.3±4.7 %) were similar to those in the group treated with conventional heart failure therapy (LVEF 21.7±4.7 %; p=0.757). After twelve months there was no statistically significant difference in LVEF between the two studied groups (LVEF 33.7±9.5 % for the immunosuppressive therapy group and 41.3±13.0 % for the conventional therapy group; p=0.175). In our study population, we proved no positive effect of combined immunosuppressive therapy on the left ventricular function over 12 months. The main limitation of the study is the small number of enrolled patients (Tab. 4, Fig. 1, Ref. 35).