ANCA titres, even of IgG subclasses, and soluble CD14 fail to predict relapses in patients with ANCA-associated vasculitis.

BACKGROUND: Antineutrophil cytoplasmic autoantibodies (ANCA) are presumed to reflect disease-activity and to be useful for guidance of immunosuppressive therapy of ANCA-associated systemic vasculitis (AASV), but with respect to conventional ANCA assays this is controversial. ANCA titres, measured in the IgG3 subclass and modern capture ELISAs, have been said to be superior predictors of relapses of AASV. METHODS: In this retrospective study serial measurements of ANCA parameters and soluble CD14 (sCD14) were performed in 169 consecutive sera over a median of 21 months in 18 patients with AASV and related to disease activity, assessed by Birmingham Vasculitis Activity Score (BVAS) for new or deteriorated (BVAS1), and for chronic disease activity (BVAS2). Fourteen patients had Wegener's granulomatosis (WG) and were C-ANCA positive with Pr 3-antibodies and four patients had microscopic polyangiitis (MPA) with P-ANCA and MPO-antibodies. In WG patients ANCA by IIF, Pr 3-ELISA for IgG, IgG1, IgG3, IgG4 and sCD14 were measured, as well as capture ELISA for Pr 3, and in MPA patients ANCA by IIF, MPO-ELISA for IgG and IgG1, IgG3, IgG4, and sCD14 respectively. In eight patients, data collection started at diagnosis, in 10 patients at remission. RESULTS: The parameters predicted neither the nine major relapses (increase of immunosuppression necessary), nor the 26 minor relapses (increase of BVAS1>2) with sufficient sensitivity (>80%) or specificity (> 90%90%), and they also failed to predict relapses within the following 2 months. ANCA-IgG3 and capture ELISA for Pr 3 were not advantageous for prediction of relapses (sensitivity 0.45 and 0.19 respectively), and sCD14 remained elevated in all samples irrespective of disease activity. CONCLUSIONS: There is no rationale for serial measurements of ANCA in AASV. For changes of therapy, the ANCA parameters should only be used in conjunction with clinical information.     

Outcome analysis of patients with vasculitis associated with antineutrophil cytoplasmic antibodies

BACKGROUND: Objective scoring systems of disease activity and disease-associated damage have proven useful in the management of patients with systemic vasculitis. PATIENTS AND METHODS: We used the recently designed Birmingham vasculitis activity score (BVAS; maximum score 63) and vasculitis damage index (VDI; maximum score 59) to assess initial activity and long-term damage, respectively, in ANCA positive patients from one center over a 3-year period. Thirty-two patients with ANCA vasculitis were identified and analyzed as an historic cohort. The median BVAS for all vasculitis patients at first presentation was 19 (range 6 - 36). Patients with Wegener's granulomatosis had a significantly higher total score and respiratory BVAS score compared to the 15 with microscopic polyangiitis. The majority of patients received standard cyclophosphamide/steroid treatment. RESULTS: At the end of follow-up (mean 24.9 months), 4 patients had died; all patients had evidence of permanent organ damage. The median total VDI score at last follow-up was 4.0 (range 0-11), with no differences between patients with Wegener's granulomatosis and microscopic polyangiitis. The VDI was not associated with the number of relapses. A high initial BVAS was found to correlate with a later high vasculitis damage index (r = 0.56). Initial renal or respiratory involvement was also associated with longterm damage in the same organ system. CONCLUSION: Although mortality from ANCA-associated vasculitis has decreased, morbidity remains a common problem. High early-disease activity may identify patients at high risk of long-term organ damage, allowing more effective individualized therapy. This hypothesis requires validation in a prospective, controlled study.     

Rituximab as rescue therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-centre experience with 15 patients

Background. B-cell depletion with rituximab, a chimeric anti-CD20antibody, is a novel treatment for refractory and relapsingANCA-associated small-vessel vasculitis. Data are limited andmost reports describe single patients or small numbers of patientsfollowed prospectively. Methods. We report a single-centre experience with 15 patientswho received rituximab for refractory or relapsing ANCA-associatedvasculitis. All patients had been treated with corticosteroidsand cyclophosphamide and a variety of other second-line immunosuppressiveagents. None of the patients had evidence of infection and receivedfour infusions of 375 mg/m² of rituximab. Disease activity wasassessed in accordance with the Birmingham Vasculitis ActivityScore (BVAS). BVAS, C-reactive protein and ANCA titres wererecorded at baseline and during follow-up. Results. B-cell depletion was achieved in all patients. Partialor complete remission was seen in 14 of 15 patients with a significantdecline in BVAS compared to baseline (P < 0.007). One patientwith granulomatous ANCA-associated vasculitis did not respondto rituximab. There were no side effects during rituximab infusion.Transient leucopenia was observed in two patients. One patientwith bronchial stenosis died of pneumonia 5.5 months after theinitiation of rituximab treatment. One initially anti-HBc-positive/HBsAg-negativepatient experienced a reactivation of hepatitis B, developedend-stage renal failure and died after refusal of dialysis. Conclusions. We report the largest case series of rituximabuse for ANCA-associated vasculitis so far. Our data supportthat the drug is capable of inducing partial or complete remissionin refractory or relapsing patients. Leucopenia and infectiouscomplications remain a matter of concern.     

The level and clinical significance of serum anti-lysosomal associated membrane protein-2 antibody in patients with ANCA-associated glomerulonephritis

Objective To investigate the relationship of the serum anti-lysosome associated membrane protein 2 (LAMP-2) antibody levels and anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis. Methods Thirty-three patients with new onset ANCA-associated glomerulonephritis and thirty healthy controls were enrolled. ANCA detection was performed using indirect immunofluorescence (IIF). Enzyme-linked immunosorbent assay (ELISA) was used to detect myeloperoxidase (MPO), proteinase-3 (PR3) and other ANCA-associated antibodies including LAMP-2. The cut-off value of the serum anti-LAMP-2 antibody was determined by a receiver operating characteristic (ROC) curve. Results The serum levels of anti-LAMP-2 antibody in new onset ANCA-associated glomerulonephritis patients were significantly higher than remission stage ANCA-associated glomerulonephritis patients and healthy controls (P＜0.05). The serum levels of anti-LAMP-2 antibody showed no visible difference between the remissionANCA-associated glomerulonephritis patients and healthy controls (P＞0.05). The levels of anti-LAMP-2 antibody showed a strong positive correlation with ESR, Scr, BUN, proteinuria, crescent proportion and Birmingham vasculitis activity score (BVAS) and a negative correlation with Ccr, Hb and Alb. Conclusions Anti-LAMP-2 antibody is correlated with the activity of ANCA-associated glomerulonephritis and the severity of renal damage. It may be a useful indicator on the activity ofANCA-associated glomerulonephritis.     

Rituximab Versus Cyclophosphamide for ANCA-Associated Vasculitis with Renal Involvement

Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the urine, and/or a rise in serum creatinine concentration attributed to vasculitis). Remission-induction regimens were RTX at 375 mg/m² × 4 or CYC at 2 mg/kg/d. CYC was replaced by AZA (2 mg/kg/d) after 3–6 months. Both groups received glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis Activity Score/Wegener''s Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two percent (102 of 197) of the patients had renal involvement at entry. Of these patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in the RTX group (41 versus 50 ml/min per 1.73 m²; P=0.05); 61% and 75% of patients treated with RTX and 63% and 76% of patients treated with CYC/AZA achieved CR by 6 and 18 months, respectively. No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were no differences between treatment groups in relapses at 6, 12, or 18 months. No differences in adverse events were observed. In conclusion, patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids.     

The clinical features of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis in Chinese children

Anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis is reported mainly in adults. Studies in children are limited. The current study retrospectively analyzed the clinical characteristics and pathology of ANCA-associated systemic vasculitis in children in our hospital during the past 7 years. Twenty-four pediatric patients were diagnosed as having ANCA-associated systemic vasculitis, including 19 patients with microscopic polyangiitis (MPA), one with Wegener’s granulomatosis (WG), three with propylthiouracil (PTU)-induced ANCA-positive vasculitis and one with anti-glomerular basement membrane (GBM) disease. Of patients with primary ANCA-associated systemic vasculitis (MPA and WG), with an average age of 10.8±2.8 (6–14) years, 18 patients (90%) were female and two (10%) were male. Nineteen patients (95%) were p-ANCA/MPO-ANCA positive and one (5%) was c-ANCA/PR3-ANCA positive. The interval between onset and diagnosis was 8.5±24.3 (0.2–108) months. The majority of the patients (85%) had multi-organ involvement. All patients had clinical evidence of renal involvement and presented with hematuria and proteinuria. Of 20 patients, 16 (80%) also had acute renal failure, and five patients were dialysis dependent. Nine patients underwent renal biopsy and were diagnosed with necrotizing and crescentic glomerulonephritis. However, six biopsies showed immune complex deposition. All patients received immunosuppressive therapy including prednisone and cyclophosphamide, and ten patients also received intravenous administration of methylprednisone pulse therapy according to their clinical situation and renal pathology. Sixteen patients achieved clinical remission, and four patients presented as treatment failure. Patients were followed up for 12.3±5.1 months (median 12 months; range 1 to 91 months). Ten patients maintained their clinical remission, and ten progressed to renal failure requiring dialysis. Our study showed that the clinical features and pathology of primary ANCA-associated systemic vasculitis in children were similar to those of adults, but there were a predominance of female patients and late diagnoses. We suggest that early recognition and prompt aggressive treatment might improve outcome.     

Elevated soluble Flt1 inhibits endothelial repair in PR3-ANCA-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-associated vasculitis compared with patients during remission and other controls. Serum levels of sFlt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-associated vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti-proteinase-3 (PR3) mAb and serum containing PR3-ANCA from patients with active vasculitis both induced a significant and sustained release of sFlt1 from monocytes, whereas anti-myeloperoxidase (MPO) mAb or polyclonal antibodies did not. However, the serum containing polyclonal PR3-ANCA did not induce release of sFlt1 from cultured human umbilical vein endothelial cells. In summary, these data suggest that anti-PR3 antibodies, and to a much lesser extent anti-MPO antibodies, increase sFlt1 during acute ANCA-associated vasculitis, leading to an antiangiogenic state that hinders endothelial repair.     

Vasculitis working group: Selected unanswered questions related to giant cell arteritis and anti-neutrophil cytoplasmic antibody-associated vasculitis

Evidence to guide assessment and management of patients with vasculitis is lacking for many important clinical questions. The evidence surrounding several common questions about management of vasculitis was reviewed. Patients with giant cell arteritis (GCA) are at risk for developing extra-cranial large vessel inflammation. Clinicians should be aware of this complication and search for large vessel involvement in patients with GCA who have ischemic symptoms. Research is needed to define optimal strategies to identify patients with such complications. Because of the hazards of chronic corticosteroid use, alternative therapies for patients with GCA have been sought but thus far no clear alternatives have been identified. Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with small-vessel vasculitis, including Wegener's granulomatosis and microscopic polyangiitis, but changes in ANCA titers should not be used as a surrogate biomarker for disease activity. Several immunosuppressive agents can be used for maintenance therapy after induction of remission in patients with ANCA-associated vasculitis, with no firm evidence that one agent is superior to others. Collectively, this review shows that more research is needed to provide a firmer body of evidence to support clinical decision-making for patients with vasculitis.     

Clinicopathological features of antineutrophil cytoplasmic antibodies-associated vasculitis in Japanese patients with IgA nephropathy

Antineutrophil cytoplasmic antibodies (ANCA) have been reported to be associated with systemic vasculitis. However, the roles of ANCA subtypes in patients with IgA nephropathy remain to be fully investigated. We describe three Japanese patients with IgA nephropathy complicated by ANCA-associated vasculitis. Two patients with IgG class ANCA developed rapidly progressive renal failure and demonstrated mesangial proliferation with extensive extracapillary proliferation and segmental glomerular necrosis. One patient with IgM class ANCA showed severe extrarenal symptoms, such as lung fibrosis and neuritis, in addition to glomerular crescent formation. All three patients received immunosuppressive therapies, including corticosteroids and cyclophosphamide. The two patients who received these treatments early showed improvement in urinary protein excretion and renal function, in accordance with a decrease in the serum titer of ANCA. However, one patient in whom serum creatinine was already elevated showed a poor response to the treatment. These results suggest that ANCA subtypes may participate in the pathogenesis of crescent formation in patients with IgA nephropathy, and that early treatment with a combination of methylprednisolone pulse therapy, oral prednisolone, and cyclophosphamide pulse therapy may be beneficial in these patients. Received: November 2, 1999 / Accepted: February 8, 2000     

Cyclosporin for the prevention of disease reactivation in relapsing ANCA-associated vasculitis

Background. In patients with ANCA-associated vasculitis the frequent development of relapses after successful initial treatment remains a major therapeutic problem. Thus a long-term prophylactic therapy with low side-effect potential is needed. As recent data suggest an involvement of T cells in the pathogenesis of ANCA-associated vasculitis, the prophylactic value of therapy with low-dose cyclosporin was investigated in seven patients (three with Wegener's granulomatosis, four with microscopic polyangiitis, all with renal involvement) who had developed at least one relapse during cyclophosphamide (CP) treatment or in the first 4 months after the end of CP therapy. Methods. After remission had been achieved for 6 months using CP and prednisolone, the CP dose was reduced (3 months 75%, 3 months 50%) and cyclosporin was added concomitantly (dose adjusted to whole blood levels 60-90 ng/ml). Cyclosporin therapy was continued for 1 year after the end of CP treatment. Results. During a mean follow-up of 24 months no patient developed a relapse. Two patients developed a herpes zoster infection. No severe bacterial infection occurred. Conclusions. These preliminary results indicate that cyclosporin can be successfully used to sustain remission in patients with a relapsing course of ANCA-associated vasculitis and renal involvement.     

Recurrence of anti-neutrophil cytoplasmic antibody vasculitis in the kidney allograft

We report a case of recurrent anti-cytoplasmic neutrophil antibody (ANCA)-associated vasculitis post kidney transplantation. A 60-year-old woman underwent uncomplicated deceased-donor kidney transplantation for end-stage renal disease (ESRD) secondary to myeloperoxidase-specific ANCA-associated vasculitis, after six years of haemodialysis, and clinical remission. Immunosuppression was with tacrolimus/mycophenolate and prednisolone after basiliximab induction therapy. Five weeks post-transplantation, an allograft biopsy, done for a rising creatinine and glomerular haematuria, revealed pauci-immune crescentic glomerulonephritis. This was treated with pulse methylprednisolone, increase in maintenance prednisolone, 7 sessions of plasma exchange, and replacement of mycophenolate with cyclophosphamide. Tacrolimus was continued throughout. After 3 months of therapy a repeat allograft biopsy showed quiescent vasculitis. The cyclophosphamide was then ceased, and mycophenolate reinstituted. The patient has maintained clinical and histological stability. Reported rates of ANCA-associated vasculitis recurrence post-kidney transplantation have varied but are low compared with other types of glomerulonephritis and seemed to have further declined in the era of modern immunosuppression. Given the low recurrence rate and excellent outcomes in suitable patients, kidney transplantation remains the optimal form of renal replacement therapy for ESRD due to ANCA-associated vasculitis. Whilst re-introduction of cyclophosphamide has been the mainstay of therapy, additional reported successful therapeutic strategies have included pulse methylprednisolone, plasma exchange and rituximab. Further study on the most effective and safest treatment options would be of use given the current paucity of data in this area.     

Recurrence of ANCA-associated vasculitis following renal transplantation in the modern era of immunosupression

Progressive glomerulonephritis and attendant end-stage renal disease (ESRD) result from antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The optimum time of kidney transplantation in patients with ESRD due to ANCA-associated vasculitis (AAV) and the risk of renal or nonrenal recurrence of vasculitis after transplantation are unknown. To answer some of these questions, we followed 35 transplant recipients with diagnoses of microscopic polyangiitis (20 patients) and Wegener's granulomatosis (15 patients). The median time from diagnosis to transplantation was 25 months with all patients being in clinical remission. Fifteen patients were ANCA-positive at time of the transplant with 13 preemptive transplants. The most common immunosuppressive strategy included antibody induction, corticosteroid, mycophenolate mofetil, and tacrolimus with acute rejection occurring in eight cases. Overall and death-censored graft survivals were 94 and 100%, respectively, 5 years post-transplantation. Nonrenal relapse occurred in three patients with a satisfactory response to treatment. No clear risk factor to relapse emerged and no detrimental effect to renal function was found. We conclude that transplantation should be considered as the treatment of choice for ESRD due to AAV. Potent antirejection regimes are well tolerated in these patients, are associated with a low risk of recurrence and an absence of AAV-related graft dysfunction.     

Treatment of antineutrophil cytoplasmic autoantibody-positive systemic vasculitis and glomerulonephritis with pooled intravenous gammaglobulin.

Antineutrophil cytoplasmic autoantibody (ANCA) is considered a serological marker for disease activity in patients with ANCA(+) systemic vasculitis. Recently, ANCA has been implicated as a pathogenic antibody that may be associated with neutrophil degranulation and release of lytic enzymes. Since intravenous gammaglobulin (IVIG) is known to contain antiidiotypic antibodies to ANCA, which could decrease the activity of the later, we chose to treat two patients with symptomatic ANCA(+) systemic vasculitis and glomerulonephritis with high-dose IVIG. The first patient, a 66-year-old man, developed rapidly progressive renal failure despite treatment with intravenous (IV) cyclophosphamide. The second patient, a 14-year-old boy, had relapsed 3 months after cessation of treatment with prednisone and cyclophosphamide. Both patients improved dramatically after treatment with IVIG, with the former recovering renal function within 11 days of therapy. In both patients, a concomitant reduction in serum ANCA titers was also observed. The second patient is currently in a sustained remission 14 months after his last IVIG dose on no other medication. These cases provide clinical evidence that IVIG has therapeutic benefit in modifying the immune-mediated injury associated with ANCA(+) systemic vasculitis and glomerulonephritis. In addition, IVIG may provide an additional safe therapeutic option to clinicians treating patient's with ANCA(+) vasculitis and glomerulonephritis who are not responsive to or are experiencing toxicity from conventional therapy.     

No association of G-463A myeloperoxidase gene polymorphism with MPO-ANCA-associated vasculitis.

BACKGROUND: The activation of neutrophils and monocytes by ANCA, resulting in the release of reactive oxygen species and proteases like myeloperoxidase (MPO), is essential to the pathogenesis of ANCA-associated vasculitis. As the A allele of the G-463A MPO gene polymorphism is associated with diminished activity of MPO, it is conceivable that the presence of this allele protects against MPO-ANCA-associated vasculitis. METHODS: Allelic frequencies of the G-463A polymorphism were studied in 119 ANCA-associated vasculitis patients, 48 with MPO-ANCA and 71 with proteinase 3 (PR3)-ANCA. RESULTS: Allelic frequencies of MPO G-463A promoter polymorphism did not differ between MPO-ANCA- and PR3-ANCA-associated vasculitis patients. Moreover, allelic distribution was similar to that of the normal population. CONCLUSIONS: The data suggest that G-463A polymorphism does not seem to contribute to either MPO-ANCA- or PR3-ANCA-associated vasculitis formation.     

Anti-neutrophil cytoplasmic antibody (ANCA)-associated microscopic polyangiitis following a suppurative wound infection.

Sir, There is strong circumstantial evidence for the role of infectionsin the development of anti-neutrophil cytoplasmic antibody (ANCA)and ANCA-associated vasculitis. We describe here, a 74-year-oldman who developed a wound infection after surgery for cancerand who was subsequently diagnosed with ANCA-associated microscopicpolyangiitis. The patient presented with 2 months of frequent bowel actions,bright     

CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

ANCA-associated vasculitis is the most frequent cause of crescentic GN. To define new molecular and/or cellular biomarkers of this disease in the kidney, we performed microarray analyses of renal biopsy samples from patients with ANCA-associated crescentic GN. Expression profiles were correlated with clinical data in a prospective study of patients with renal ANCA disease. CC chemokine ligand 18 (CCL18), acting through CC chemokine receptor 8 (CCR8) on mononuclear cells, was identified as the most upregulated chemotactic cytokine in patients with newly diagnosed ANCA-associated crescentic GN. Macrophages and myeloid dendritic cells in the kidney were detected as CCL18-producing cells. The density of CCL18⁺ cells correlated with crescent formation, interstitial inflammation, and impairment of renal function. CCL18 protein levels were higher in sera of patients with renal ANCA disease compared with those in sera of patients with other forms of crescentic GN. CCL18 serum levels were higher in patients who suffered from ANCA-associated renal relapses compared with those in patients who remained in remission. Using a murine model of crescentic GN, we explored the effects of the CCL18 murine functional analog CCL8 and its receptor CCR8 on kidney function and morphology. Compared with wild-type mice, Ccr8^−/− mice had significantly less infiltration of pathogenic mononuclear phagocytes. Furthermore, Ccr8^−/− mice maintained renal function better and had reduced renal tissue injury. In summary, our data indicate that CCL18 drives renal inflammation through CCR8-expressing cells and could serve as a biomarker for disease activity and renal relapse in ANCA-associated crescentic GN.     

Relationship between ANCA and disease activity in small vessel vasculitis patients with anti-MPO ANCA.

BACKGROUND: We analysed the usefulness of antineutrophil cytoplasmic antibodies (ANCA) as a marker of clinical activity in patients with small vessel vasculitis associated with anti-myeloperoxidase (MPO) ANCA. METHODS: We studied a group of 25 patients, 15 with microscopic polyangitis and 10 with renal limited vasculitis, so-called rapidly progressive glomerulonephritis type III. The clinical and serological follow-up was accomplished quarterly over an average of 2.79 +/- 2.08 years (range 0.25-6 years). ANCA was analysed by indirect immunofluorescence and enzyme-linked immunosorbent assays (ELISAs). RESULTS: At the time of diagnosis, all patients were ANCA positive (P-ANCA and anti-MPO). Following a standardized treatment, all patients except one achieved complete remission of vasculitis in <3 months. One patient suddenly died during the active phase (1 month of follow-up) and with positive ANCA. Seroconversion from positive to negative occurred in 24/25 patients (96%). Eighteen of these 24 patients (75%) achieved the seroconversion within the first 6 months. During the follow-up, two patients had four major relapses, all of them associated with positive ANCA. ANCA seroconversion from negative to positive was observed in one patient with microscopic polyangitis without clinical relapse of vasculitis. CONCLUSION: ANCA should be used in conjunction with other markers of disease activity in the management of microscopic polyangitis and renal limited vasculitis patients with anti-MPO ANCA.     

血清抗中性粒细胞胞浆抗体滴度检测对移植肾急性血管排斥的诊断价值

动态观察了４例移植肾急性血管排斥患者经甲基泼尼松龙和环磷酰胺双冲击治疗前后血清抗中性粒细胞胞浆抗体（ＡＮＣＡ）滴度的动态变化，分析患者治疗前后临床实验室检查和肾组织病理变化。结果：（１）病情处于急性排斥期，血清ＡＮＣＡ滴度升高；（２）治疗后，临床症状减轻，肾功能改善，肾组织病理趋于正常时，ＡＮＣＡ滴度降低；（３）随访半年，移植肾排斥缓解，４例患者血清抗髓过氧化物酶抗体（ＭＰＯ－ＡＮＣＡ）均转为阴性，２例荧光法ＡＮＣＡ（ＩＦ－ＡＮＣＡ）转为阴性。结果表明，血清ＡＮＣＡ滴度的动态变化可以作为监测移植肾急性血管排斥的一项指标，对早期诊断和指导治疗有重要意义     

Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis.

BACKGROUND: Vaccination against influenza has been suggested to induce relapses of ANCA-associated vasculitis but evidence is lacking. In this study, we assessed whether vaccination against influenza increases the occurrence of relapses in patients with ANCA-associated vasculitis. METHODS: Two hundred and thirty consecutive patients with ANCA-associated vasculitis from our out-patient clinics of a tertiary referral center, with at least 1 year of follow-up, were included. Retrospectively, the relapse rate per 100 patients at risk in patients who had been vaccinated against influenza within the preceding year and in patients who not had been vaccinated within that time period were calculated. RESULTS: The relapse rate per 100 patients at risk was lower in patients who had been vaccinated against influenza (3.4) than in patients who had not been vaccinated (6.3), when analyzed for the entire year and for every quarter of the year. Also, the disease-free survival per separate year according to the vaccination status was lower in all 5 years in patients who had been vaccinated, being statistically significant in 2 years. CONCLUSION: Vaccination against influenza does not increase the relapse rate in patients with ANCA-associated vasculitis.     

ANCA-positive crescentic glomerulonephritis associated with minocycline therapy

Minocycline is an oral antibiotic widely used for the long-term treatment of acne and rheumatoid arthritis. A few patients develop antineutrophil cytoplasmic antibodies (ANCAs) during minocycline therapy. In this report, the authors describe a case of severe pauci-immune crescentic and necrotizing glomerulonephritis associated with positive cytoplasmic ANCA (C-ANCA) titers and proteinase 3 (PR3) levels after minocycline therapy. Discontinuation of minocycline and initiation of immunosuppressive treatment resulted in improvement of renal function and decline in C-ANCA titers and PR3 levels. A high degree of suspicion, testing for ANCA titers, prompt discontinuation of the drug, and initiation of immunosuppressive treatment are crucial to the diagnosis and treatment of drug-induced ANCA-associated glomerulonephritis.