Advancing autoimmune Rheumatic disease treatment: CAR-T Cell Therapies - Evidence, Safety, and future directions.

INTRODUCTION: Despite advancements in managing autoimmune rheumatic diseases (ARDs) with existing treatments, many patients still encounter challenges such as inadequate responses, difficulty in maintaining remission, and side effects. Chimeric Antigen Receptor (CAR) T-cell therapy, originally developed for cancer, has now emerged as a promising option for cases of refractory ARDs. METHODS: A search of the literature was conducted to compose a narrative review exploring the current evidence, potential safety, limitations, potential modifications, and future directions of CAR-T cells in ARDs. RESULTS: CAR-T cell therapy has been administered to patients with refractory ARDs, including systemic lupus erythematosus, antisynthetase syndrome, and systemic sclerosis, demonstrating significant improvement. Notable responses include enhanced clinical symptoms, reduced serum autoantibody titers, and sustained remissions in disease activity. Preclinical and in vitro studies using both animal and human samples also support the efficacy and elaborate on potential mechanisms of CAR-T cells against antineutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis. While cautious monitoring of adverse events, such as cytokine release syndrome, is crucial, the therapy appears to be highly tolerable. Nevertheless, challenges persist, including cost, durability due to potential CAR-T cell exhaustion, and manufacturing complexities, urging the development of innovative solutions to further enhance CAR-T cell therapy accessibility in ARDs. CONCLUSIONS: CAR-T cell therapy for refractory ARDs has demonstrated high effectiveness. While no significant warning signs are currently reported, achieving a balance between therapeutic efficacy and safety is vital in adapting CAR-T cell therapy for ARDs. Moreover, there is significant potential for technological advancements to enhance the delivery of this treatment to patients, thereby ensuring safer and more effective disease control for patients.

High-resolution epitope mapping of commercial antibodies to ANCA antigens by yeast surface display.

Epitope mapping provides critical insight into antibody-antigen interactions. Epitope mapping of autoantibodies from patients with autoimmune diseases can help elucidate disease immunogenesis and guide the development of antigen-specific therapies. Similarly, epitope mapping of commercial antibodies targeting known autoantigens enables the use of those antibodies to test specific hypotheses. Anti-Neutrophil Cytoplasmic Autoantibody (ANCA) vasculitis results from the formation of autoantibodies to multiple autoantigens, including myeloperoxidase (MPO), proteinase-3 (PR3), plasminogen (PLG), and peroxidasin (PXDN). To perform high-resolution epitope mapping of commercial antibodies to these autoantigens, we developed a novel yeast surface display library based on a series of >5000 overlapping peptides derived from their protein sequences. Using both FACS and magnetic bead isolation of reactive yeast, we screened 19 commercially available antibodies to the ANCA autoantigens. This approach to epitope mapping resulted in highly specific, fine epitope mapping, down to single amino acid resolution in many cases. Our study also identified cross-reactivity between some commercial antibodies to MPO and PXDN, which suggests that patients with apparent autoantibodies to both proteins may be the result of cross-reactivity. Together, our data validate yeast surface display using maximally overlapping peptides as an excellent approach to linear epitope mapping.

Venovenous Extracorporeal Membrane Oxygenation in Diffuse Alveolar Hemorrhage Secondary to Anti-neutrophil Cytoplasmic Autoantibody-associated Vasculitis: Starting without Systemic Anticoagulation.

Regarding extracorporeal membrane oxygenation (ECMO) support against hemorrhagic conditions, there seems to be a dilemma when deciding between maintaining the circuit patency by systemic anticoagulation and increasing the risk of bleeding. We herein report two cases of diffuse alveolar hemorrhage (DAH) caused by myeloperoxidase (MPO) anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) successfully treated with venovenous (VV)-ECMO support, both initially started without systemic anticoagulation. Under anticoagulation-free ECMO management, we should consider the shortcomings of frequent circuit exchange and hemorrhagic diathesis related to circuit-induced disseminated intravascular coagulation (DIC).

Clinicopathological Characteristics and Influencing Factors of Renal Vascular Lesions in Anti-neutrophil Cytoplasmic Autoantibody-Related Renal Vasculitis.

The purpose of this study was to evaluate the clinicopathological features of different degrees of extraglomerular renal vascular lesions (RVLs) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis and explore their clinical determinants. This is a retrospective study of 186 patients with ANCA-associated renal vasculitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019. The patients who met the inclusion criteria were divided into non-renal RVLs, mild RVLs, moderate RVLs, and severe RVLs. It was found that there were significant differences in serum creatinine (SCR), estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate (ESR), high-density lipoprotein (HDL), systolic blood pressure (SBP), the prevalence rate of hypertension, the proportion of normal glomeruli, and the proportion of sclerotic glomeruli and interstitial fibrosis integral. SCR and ESR are independent risk factors for RVLs. The participants were followed up for 1 year, and the progression to end-stage renal disease (ESRD) and death was defined as endpoint events. We found that the survival rate of patients without RVLs was significantly higher than that of patients with RVLs and that the RVLs were an independent risk factor for ESRD or death. Early intervention in the progression of RVLs can improve the prognosis.

New Insights Into Novel Therapeutic Targets in ANCA-Associated Vasculitis.

Biologics targeting inflammation-related molecules in the immune system have been developed to treat rheumatoid arthritis (RA), and these RA treatments have provided revolutionary advances. Biologics may also be an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, particularly in patients with resistance to standard treatments. Despite the accumulation of clinical experience and the increasing understanding of the pathogenesis of vasculitis, it is becoming more difficult to cure vasculitis. The treatment of vasculitis with biologics has been examined in clinical trials, and this has also enhanced our understanding of the pathogenesis of vasculitis. A humanized anti-interleukin-5 monoclonal antibody known as mepolizumab was recently demonstrated to provide clinical benefit in the management of eosinophilic granulomatosis with polyangiitis in refractory and relapsing disease, and additional new drugs for vasculitis are being tested in clinical trials, while others are in abeyance. This review presents the new findings regarding biologics in addition to the conventional immunosuppressive therapy for ANCA-associated vasculitis.

Clinical features and outcomes of anti-neutrophil cytoplasmic autoantibody-associated vasculitis in Chinese elderly and very elderly patients.

PURPOSE: Anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is predominantly a disease of the elderly, and the incidence increases with age. However, there are few data focusing on the clinical features in elderly onset AAV, especially in very elderly onset AAV in China. The aim of this study was to explore whether elderly onset AAV shows any specific clinical features and outcomes in Chinese patients. METHODS: We performed a retrospective study in Xiangya Hospital, a mixed tertiary medical center in south China. A total of 177 patients presenting with AAV were included between January 1, 2010 and December 31, 2017. Patients were divided into younger group (age < 65 years) and older group (age ≥ 65 years) which was sub-divided into elderly group (age 65-74 years) and very elderly group (age ≥ 75 years). And their medical records were analyzed by retrospective review. RESULTS: We found patients in the very elderly group had more chest and cardiovascular involvement (P = 0.033 and P = 0.017). Older AAV patients had less renal involvement and lower serum C4 level (P = 0.013 and P = 0.003). Very elderly AAV patients had lower platelet counts. Patients in the younger group had a higher level of BVAS among three groups (P < 0.05 younger group vs. very elderly group; P < 0.05 younger group vs. elderly group). There were no significant difference in the proportion of ESRD patients among the three groups (P = 0.473). Patients in the very elderly group had the poorest patient survival (P = 0.002). CONCLUSION: Older AAV patients had less renal involvement, lower serum C4 level and BVAS. The very elderly group got the most chest and cardiovascular involvement and had lower platelet counts. Older age is associated with higher mortality in AAV patients.

Association between statin use and incidence of relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-center retrospective cohort study.

Several studies have shown the efficacy of statins for some autoimmune disorders caused by anti-inflammatory and immunomodulatory reactions. However, little information is available about the impact of statins on relapse in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). We performed the first investigation examining whether statin use has an effect on suppressing the first relapse of AAV in Japanese patients with AAV. This single-center retrospective cohort study included 98 consecutive patients with newly diagnosed AAV from Aichi Medical University Hospital, Japan between March 2009 and December 2017. Time to first relapse from the first remission was compared between 36 patients in the statin group and 62 patients in the non-statin group using multivariate Cox proportional hazard models, which were adjusted for clinically relevant factors. During the follow-up period (median, 24 months; interquartile range, 9-50 months), 35 (97.2%) patients in the statin group achieved remission, whereas 56 (90.3%) patients achieved remission in the non-statin group (P = 0.201). After achieving the first remission, 9 (25.7%) patients in the statin group and 29 (51.8%) patients in the non-statin group had at least one relapse. Multivariate Cox proportional hazard models revealed that statin use was significantly associated with a lower incidence of relapse compared with non-statin use (multivariate-adjusted hazard ratio = 0.41, 95% confidence interval: 0.18-0.92; P = 0.031). Patients with statin use were associated with a lower incidence of relapse in AAV. Our results should be assessed in well-designed randomized controlled trials.

Treatment Outcomes of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Patients Over Age 75 Years: A Meta-Analysis.

BACKGROUND: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. METHODS: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. RESULTS: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25-36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09-0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16-0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15-3.35]). CONCLUSION: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

Neutrophil myeloperoxidase harbors distinct site-specific peculiarities in its glycosylation.

Anti-neutrophil cytoplasmic autoantibodies (ANCAs) are directed against lysosomal components of neutrophils. ANCAs directed to proteinase 3 and myeloperoxidase (MPO) in particular are associated with distinct forms of small vessel vasculitides. MPO is an abundant neutrophil-derived heme protein that is part of the antimicrobial defense system. The protein is typically present in the azurophilic granules of neutrophils, but a large portion may also enter the extracellular space. It remains unclear why MPO is frequently the target of antibody-mediated autoimmune responses. MPO is a homodimeric glycoprotein, posttranslationally modified with complex sugars at specific sites. Glycosylation can strongly influence protein function, affecting its folding, receptor interaction, and backbone accessibility. MPO potentially can be heavily modified as it harbors 5 putative N-glycosylation sites (10 in the mature dimer). Although considered important for MPO structure and function, the full scope and relative abundance of the glycans attached to MPO is unknown. Here, combining bottom-up glycoproteomics and native MS approaches, we structurally characterized MPO from neutrophils of healthy human donors. We quantified the relative occupancy levels of the glycans at each of the five sites and observed complex heterogeneity and site-specific glycosylation. In particular, we detected glycosylation phenotypes uncommon for glycoproteins in the extracellular space, such as a high abundance of phosphorylated high-mannose species and severely truncated small glycans having the size of paucimannose or smaller. We hypothesize that the atypical glycosylation pattern found on MPO might contribute to its specific processing and presentation as a self-antigen by antigen-presenting cells.

Improvement of Alveolar Hemorrhaging in an Elderly and Renally Impaired Patient with Relapsing Anti-neutrophil Cytoplasmic Autoantibody-associated Vasculitis by Single Infusion of Rituximab.

Rituximab (RTX) has become a therapeutic option for inducing remission of anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV). However, the optimum dosage of RTX to induce remission of AAV and reduce adverse events, such as infection, remains unclear. We herein report an elderly and renally impaired patient with alveolar hemorrhaging due to refractory AAV who was successfully treated with single infusion of RTX. Single infusion of RTX may be a therapeutic option in refractory AAV patients who are vulnerable to infections.

Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils.

Our previous study demonstrated that plasma levels of complement factor H (FH) were inversely associated with the disease activity of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In addition to serving as an inhibitor of the alternative complement pathway, there is increasing evidence demonstrating direct regulatory roles of FH on several cell types. Here, we investigated the role of FH in the process of ANCA-mediated activation of neutrophils and neutrophil-endothelium interaction. We demonstrated that FH bound to neutrophils by immunostaining and flow cytometry. Interestingly, ANCA-induced activation of neutrophils, including respiratory burst and degranulation, was inhibited by FH. Although FH enhanced neutrophils adhesion and migration toward human glomerular endothelial cells (hGEnCs), it inhibited ANCA-induced activation of neutrophils in the coculture system of hGEnCs and neutrophils. Moreover, the activation and injury of hGEnCs, reflected by the level of endothelin-1 in the supernatant of cocultures, was markedly reduced by FH. However, we found that FH from patients with active AAV exhibited a deficient ability in binding neutrophils and inhibiting ANCA-induced neutrophil activation in fluid phase and on endothelial cells, as compared with that from healthy controls. Therefore, our findings indicate a novel role of FH in inhibiting ANCA-induced neutrophil activation and protecting against glomerular endothelial injury. However, FH from patients with active AAV are deficient in their ability to bind neutrophils and inhibit neutrophil activation by ANCA. It further extends the current understanding of the pathogenesis of AAV, thus providing potential clues for intervention strategies.

Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.

The impact of intravenous methylprednisolone pulses on renal survival in anti-neutrophil cytoplasmic antibody associated vasculitis with severe renal injury patients: a retrospective study.

BACKGROUND: High-dose methylprednisolone pulses were one of the main treatments for anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitides (AAV) but had obvious side effects. We aimed to know the impact on renal survival and identify the prognostic factors of this treatment in Chinese AAV patients with severe renal involvement. METHODS: One hundred and eleven AAV patients with an estimated glomerular filtration rate (eGFR) of 10ml/min/1.73 m2 or less at admission were included. The MP group (n = 57) received intravenous methylprednisolone 500 mg/d for 3 days, while the control group (n = 54) had not. The outcomes and adverse events between two groups were compared. Besides, predictors for dialysis independence and good response of intravenous methylprednisolone were analyzed using Cox regression analysis and ROC curves respectively. RESULTS: Their median duration of follow-up was 31 (range 3 to 134) months. Eleven patients in MP group and 20 patients in control group were died (P = 0.056). Twenty-one patients (36.8%) in MP group and 29 patients (53.7%) in control group were on maintaining dialysis (P = 0.088). Twenty-one patients in MP group remained dialysis independent, more than those in control group (4 patients, P <0.01). Urine protein creatinine ratio (hazard ratio 1.730, 95% confidence interval 1.029 to 2.909, P = 0.039) and the treatment of intravenous methylprednisolone pulses (hazard ratio 0.362, 95% confidence interval 0.190 to 0.690, P = 0.002) were the independent risk factors for dialysis independence. Those patients with serum creatinine≥855µmol/L and urine protein ≥3.7g/24h at admission may have worse responses to intravenous methylprednisolone pulses (sensibility 56.7%, specificity 85.0%, PPV 100.0% and NPV57.1%). CONCLUSIONS: Intravenous methylprednisolone pulses could improve the long-term outcome in term of dialysis independence and tend to decrease mortality for Chinese AAV patients with severe renal involvement.

Microscopic polyangiitis: Atypical presentation with extensive small bowel necrosis, diffuse alveolar hemorrhage, and renal failure.

Microscopic polyangiitis is an uncommon systemic vasculitis of varying severity that is associated with myeloperoxidase (MPO) and perinuclear antineutrophil cytoplasmic (p-ANCA) antibodies. The most commonly affected organs are the lungs and kidneys. We report on a very unusual case of microscopic polyangiitis presenting with severe mesenteric ischemia in addition to diffuse alveolar hemorrhage and acute renal failure. The patient was initially diagnosed with acute pancreatitis at an outside facility given his severe abdominal pain and elevated pancreatic enzymes. Further investigations after transfer to our facility determined that the patient was actually suffering from a severe exacerbation of previously diagnosed microscopic polyangiitis. He quickly developed diffuse alveolar hemorrhage (DAH) necessitating intubation and acute kidney injury (AKI) requiring dialysis. He subsequently developed mesenteric ischemia and bowel necrosis resulting in emergent laparotomy and extensive small bowel resection. Physicians need to be aware that microscopic polyangiitis can very rarely present with severe involvement of the abdominal viscera and mesenteric vessels. Severe disease necessitates the use of high dose IV steroids, rituximab or cyclophosphamide, and plasma exchange (PLEX).

Neutrophil anti-neutrophil cytoplasmic autoantibody proteins: bactericidal increasing protein, lactoferrin, cathepsin, and elastase as serological markers of inflammatory bowel and other diseases.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract comprising Crohn's disease and ulcerative colitis. Although the pathogenesis of the disease is not clearly defined yet, environmental, genetic and other factors contribute to the onset of the disease. Apart from the clinical and histopathological findings, several serological biomarkers are also employed to detect IBD. One of the most thoroughly studied biomarker is anti-neutrophil cytoplasmic autoantibody (ANCA). We herein provide an overview of the current knowledge on the use of ANCA and certain ANCA proteins, such as bactericidal increasing protein, lactoferrin, cathepsin G and elastase, as serological markers for IBD and other diseases.

Hemorrhagic complications associated with PR3-ANCA crescentic glomerulonephritis.

Hemorrhagic complications of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis are life-threatening conditions. Of these, alveolar hemorrhage is the most common and well-described hemorrhagic complication and is a prominent component of the pulmonary-renal syndrome. The clinical presentation of alveolar hemorrhage is highly variable ranging from mild to serious disease that may require respiratory support. Less attention has been directed at hemorrhagic complications that have been reported in other organs and which may be as severe or more severe with regard to morbidity and mortality. For example, among the most serious non-pulmonary complications are those related to cerebral and gastrointestinal hemorrhage. Cerebral hemorrhage is the clearly the most critical issue with a persistent high mortality rate. The prognosis of gastrointestinal hemorrhage, once an ominous complication has improved with medical and surgical intervention. Not to be dismissed are the consequences of hemorrhagic issues related to skin, soft tissue or muscle involvement. Muscle hematomas, while rare, also accompanied by significant morbidity.

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model.

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis.

Anti-complement therapy for glomerular diseases.

A major shift in our understanding of glomerular diseases is the focus on which components of the complement pathway are involved in mediating kidney injury. For example, the membranoproliferative glomerulonephritis lesion is no longer classified solely by ultrastructural findings on biopsy and is now divided into immune-complex-mediated lesions vs complement-mediated lesions. In turn, this emphasis on complement leads to interest in therapies that target complement as potential disease-modifying agents. Eculizumab, the first available anti-complement therapy, blocks at the level of C5 and has revolutionized the treatment of atypical hemolytic uremic syndrome. Whether this agent will work equally well for the far more heterogeneous entities of C3 glomerulonephritis and dense deposit disease remains unclear. Instead, newer agents that target C3 may turn out to be the most effective and specific therapy for these C3 glomerulopathies.

Successful treatment for thrombotic thrombocytopenic purpura complicated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated vasculitis.

Thrombotic thrombocytopenic purpura (TTP) complicated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis is rare and generally has a serious prognosis. We report a case wherein TTP was successfully treated with repeated plasma exchange (PE) and MPO-ANCA-associated vasculitis with corticosteroids. The renal function consequently improved such that haemodialysis could be discontinued and the patient was discharged without any significant complications.