Anti-glomerular basement membrane disease with rupture of the newly formed bilateral corpus luteum cysts: A case report.

RATIONALE: Anti-glomerular basement membrane (anti-GBM) disease during gestation is sparse and even rarer when combined with bilateral large corpus luteum cysts. In this case, we report a case of anti-GBM disease in the early stage of pregnancy with ruptured newly formed bilateral large corpus luteum cysts. PATIENT CONCERNS: A 24-year-old female was initially diagnosed with anti-GBM disease. During treatment, abdominal distention and vaginal bleeding successively staged. The results of the first gynecological ultrasound and abdominal CT were negative. DIAGNOSIS: Based on the dynamic imaging change of the ovaries, the elevated human chorionic gonadotropin (hCG) and sex hormones, and the pathological findings, a diagnosis of anti-GBM disease with rupture of the newly formed bilateral corpus luteum cysts during early pregnancy was considered. INTERVENTIONS: The patient was treated with corticosteroids, plasma-exchange along with intensive hemodialysis. Then, to confirm the diagnosis, laparoscopic debulking of bilateral ovarian cysts and curettage were performed. OUTCOMES: After treatment, the anti-GBM antibody titer declined and the condition of the patient was still stable 2 months following discharge. LESSONS: As clinicians, we should be aware that even if the first imaging tests are negative, the relevant indicators should be reviewed dynamically based on the condition of the patients. Additionally, this case raised the question of whether anti-GBM disease was associated with pregnancy and giant corpus luteum cysts, which needs further investigations.

Understanding the Gut-Kidney Axis in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: An Analysis of Gut Microbiota Composition.

Increasing evidence suggested that gut microbiota played critical roles in developing autoimmune diseases. This study investigated the correlation between gut microbiota and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with kidney injury. We analyzed the fecal samples of 23 AAV patients with kidney injury using a 16s RNA microbial profiling approach. The alpha-diversity indexes were significantly lower in AAV patients with kidney injury than healthy controls (Sobs P < 0.001, Shannon P < 0.001, Chao P < 0.001). The beta-diversity difference demonstrated a significant difference among AAV patients with kidney injury, patients with lupus nephritis (LN), and health controls (ANOSIM, p = 0.001). Among these AAV patients, the Deltaproteobacteria, unclassified_o_Bacteroidales, Prevotellaceae, Desulfovibrionaceae Paraprevotella, and Lachnospiraceae_NK4A136_group were correlated negatively with serum creatinine, and the proportion of Deltaproteobacteria, unclassified_o_Bacteroidales, Desulfovibrionaceae, Paraprevotella, and Lachnospiraceae_NK4A136_group had a positive correlation with eGFR. In conclusion, the richness and diversity of gut microbiota were reduced in AAV patients with kidney injury, and the alteration of gut microbiota might be related with the severity of kidney injury of AAV patients. Targeted regulation of gut microbiota disorder might be a potential treatment for AAV patients with kidney injury.

Double Filtration Plasmapheresis in the Treatment of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis with Severe Kidney Dysfunction.

BACKGROUND: Therapeutic plasma exchange (TPE) has been recommended by guidelines for the treatment of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) with severe kidney dysfunction. In recent years, some researchers have proposed that double-filtration plasmapheresis (DFPP) can also be used effectively in the treatment of these patients, but the difference between the 2 modalities of plasmapheresis is not clear. METHODS: In this retrospective cohort study of AAV patients with serum creatinine ≥500 µmol/L from March 2013 to July 2018 who received TPE or DFPP treatment, we compared TPE and DFPP in terms of the changes of clinical parameters before and after plasmapheresis, the rates of adverse events during plasmapheresis, and kidney and patient survival during follow-up. RESULTS: Forty-two AAV patients with kidney injury were included in this study. Twenty patients were treated with TPE and 22 patients were treated with DFPP. All patients were followed up for a median of 22 months. In each group, there were 10 deaths, and 6 patients developed end-stage kidney disease (ESKD). There were no significant differences between TPE and DFPP in terms of the changes of renal function or other laboratory results after treatment. During the plasmapheresis treatment, there was no significant difference in the rate of adverse events (p = 0.67). During the follow-up, there was no difference between the groups regarding the level of serum creatinine for patients with kidney recovery. The hazard ratio (HR) for TPE compared to DFPP for the outcome of ESKD was 0.92 (95% CI 0.45-1.9; p = 0.79) and the HR for death was 1.11 (95% CI 0.45-2.76; p = 0.82). CONCLUSION: There were no differences in short-term effectiveness, safety, or long-term outcomes between the 2 modalities of plasmapheresis. Our study suggests that DFPP may be a choice of plasmapheresis for AAV patients with severe kidney injury especially in countries and regions with limited blood resources.

Toll-like Receptors as Potential Therapeutic Targets in Kidney Diseases.

Toll-like Receptors (TLRs) are members of pattern recognition receptors and serve a pivotal role in host immunity. TLRs response to pathogen-associated molecular patterns encoded by pathogens or damage-associated molecular patterns released by dying cells, initiating an inflammatory cascade, where both beneficial and detrimental effects can be exerted. Accumulated evidence has revealed that TLRs are closely associated with various kidney diseases but their roles are still not well understood. This review updated evidence on the roles of TLRs in the pathogenesis of kidney diseases including urinary tract infection, glomerulonephritis, acute kidney injury, transplant allograft dysfunction and chronic kidney diseases.

Kinin B1 Receptor Is Important in the Pathogenesis of Myeloperoxidase-Specific ANCA GN.

BACKGROUND: Myeloperoxidase-specific ANCA (MPO-ANCA) are implicated in the pathogenesis of vasculitis and GN. Kinins play a major role during acute inflammation by regulating vasodilatation and vascular permeability and by modulating adhesion and migration of leukocytes. Kinin system activation occurs in patients with ANCA vasculitis. Previous studies in animal models of GN and sclerosing kidney diseases have demonstrated protective effects of bradykinin receptor 1 (B1R) blockade via interference with myeloid cell trafficking. METHODS: To investigate the role of B1R in a murine model of MPO-ANCA GN, we evaluated effects of B1R genetic ablation and pharmacologic blockade. We used bone marrow chimeric mice to determine the role of B1R in bone marrow-derived cells (leukocytes) versus nonbone marrow-derived cells. We elucidated mechanisms of B1R effects using in vitro assays for MPO-ANCA-induced neutrophil activation, endothelial adherence, endothelial transmigration, and neutrophil adhesion molecule surface display. RESULTS: B1R deficiency or blockade prevented or markedly reduced ANCA-induced glomerular crescents, necrosis, and leukocyte influx in mice. B1R was not required for in vitro MPO-ANCA-induced neutrophil activation. Leukocyte B1R deficiency, but not endothelial B1R deficiency, decreased glomerular neutrophil infiltration induced by MPO-ANCA in vivo. B1R enhanced ANCA-induced neutrophil endothelial adhesion and transmigration in vitro. ANCA-activated neutrophils exhibited changes in Mac-1 and LFA-1, important regulators of neutrophil endothelial adhesion and transmigration: ANCA-activated neutrophils increased surface expression of Mac-1 and increased shedding of LFA-1, whereas B1R blockade reduced these effects. CONCLUSIONS: The leukocyte B1R plays a critical role in the pathogenesis of MPO-ANCA-induced GN in a mouse model by modulating neutrophil-endothelial interaction. B1R blockade may have potential as a therapy for ANCA GN and vasculitis.

The relationship between thyroid dysfunction and nephrotic syndrome: a clinicopathological study.

Abnormalities of thyroid function are common in patients with nephrotic syndrome (NS). However, a limited number of studies have reported on the association between clinicopathologic features and thyroid dysfunction in patients with NS. We retrospectively studied 317 patients who had been definitively diagnosed with NS. The NS patients with thyroid dysfunction showed higher urine protein, creatinine and lipid levels and lower albumin and hemoglobin than those with normal thyroid function, with no significant differences of pathological types. After dividing thyroid dysfunction groups into five subgroups, interestingly, membranous nephropathy was the most common pathologic type, both in normal thyroid group and in subclinical hypothyroidism group (40.4% and 46.7%, respectively), followed by minimal change disease (28.1% and 21.7%, respectively); while in the hypothyroid, low T3, and low T3T4 groups minimal change disease is now the leading type (48.8%, 33.3% and 38.6%, respectively). High levels of urinary protein, creatinine, cholesterol, and platelets were independent risk factors predicting thyroid dysfunction, while higher albumin and hemoglobin were protective factors. We demonstrated that the type of renal pathology was different among NS patients in different thyroid dysfunction subgroups. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with NS.

Simultaneous occurrence of IgG4-related Tubulointerstitial nephritis and colon adenocarcinoma with hepatic metastasis: a case report and literature review.

BACKGROUND: Understanding the uncommon association of IgG4-related disease with other disorders is essential for the accurate diagnosis and effective treatment of patients. To the best of our knowledge, there have been only few reports of patients with IgG4-related kidney disease coexisting with metastasis of malignancy. Here, we report a rare case of simultaneous occurring IgG4-related tubulointerstitial nephritis and colon adenocarcinoma with hepatic metastasis. CASE PRESENTATION: A 71-year-old Chinese man presented with dysuria and was initially diagnosed as benign prostatic hyperplasia for one year. He was admitted to the hospital for surgery. After admission, the renal function tests revealed a rapid increase of serum creatinine from 291.0 µmol/L to 415 µmol/L. The hemoglobin level was 89 g/L. Fecal occult blood testing was positive. Urinalysis revealed mild proteinuria. The serum IgG4 level was 13.9 g/L. The abdominal imaging examination revealed multiple solid nodules in the liver. The gastrointestinal endoscopy combined with the biopsy revealed colon adenocarcinoma. Kidney biopsy showed massive IgG4-positive plasma cells and storiform fibrosis infiltration in the tubulointerstitial area, thus establishing the diagnosis of IgG4-related tubulointerstitial nephritis. Corticosteroid therapy was initiated, and subsequently, the renal function dramatically improved without the diminution of the liver nodules. The liver biopsy was performed and a diagnosis of metastatic colon adenocarcinoma was confirmed. CONCLUSIONS: We here reported a rare case of simultaneous occurring of IgG4-related tubulointerstitial nephritis, colon adenocarcinoma with hepatic metastasis. The case highlights the importance of screening for malignancy in patients with IgG4-related disease, and the nature of the mass in other organs of patients with coexisting IgG4-related disease and malignancy should be carefully checked.

Immunoglobulin G4-related Kidney Disease Associated With Autoimmune Hemolytic Anemia.

Awareness of the uncommon associated clinical manifestations of immunoglobulin G4 (IgG4)-related kidney disease is essential for the early diagnosis and effective treatment of patients. To the best of our knowledge, there have been few reports of patients with IgG4-related kidney disease associated with autoimmune hemolytic anemia. We here report a rare case of IgG4-related kidney disease associated with autoimmune hemolytic anemia. A 70-year-old man with kidney dysfunction and severe anemia had been diagnosed with chronic kidney disease and treated without any improvement. On admission, he had a high serum creatinine level, low hemoglobin level, positive direct Coombs test, and mild proteinuria. Serum IgG and IgG4 were elevated. Kidney biopsy showed marked infiltration of IgG4-positive plasma cells and storiform fibrosis in the interstitial compartment, which confirmed the diagnosis of IgG4-related kidney disease. Corticosteroid therapy was initiated, and subsequently, the kidney dysfunction and anemia dramatically improved.

Pharmacological Inhibition of Macrophage Toll-like Receptor 4/Nuclear Factor-kappa B Alleviates Rhabdomyolysis-induced Acute Kidney Injury.

BACKGROUND:: Acute kidney injury (AKI) is the most common and life-threatening systemic complication of rhabdomyolysis. Inflammation plays an important role in the development of rhabdomyolysis-induced AKI. This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role of macrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. METHODS:: C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis, and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0.5 h before molding. Serum creatinine levels, creatine kinase, the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, and hematoxylin and eosin stainings of kidney tissues were tested. The infiltration of macrophage, mRNA levels, and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques, reverse transcriptase-quantitative polymerase chain reaction, and Western blotting, respectively. In vitro, macrophage RAW264.7 was stimulated by ferrous myoglobin; the cytokines, TLR4 and NF-κB expressions were also detected. RESULTS:: In an in vivo study, using CLI-095 or PDTC to block TLR4/NF-κB, functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages (P < 0.01). CLI-095 or PDTC administration suppressed proinflammatory cytokine (TNF-α, IL-6, and IL-1ß) production and macrophage infiltration into the kidney (P < 0.01). Moreover, in an in vitro study, CLI-095 or PDTC suppressed myoglobin-induced expression of TLR4, NF-κB, and proinflammatory cytokine levels in macrophage RAW264.7 cells (P < 0.01). CONCLUSION:: The pharmacological inhibition of TLR4/NF-κB exhibited protective effects on rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.

The association between anti-plasminogen antibodies and disease activity in ANCA-associated vasculitis.

OBJECTIVE: Previous studies have shown that in patients with ANCA-associated vasculitis (AAV), anti-plasminogen antibodies were associated with reduced renal function and the presence of fibrinoid necrosis and cellular crescents in renal histology. The purpose of the current study was to investigate whether anti-plasminogen antibodies are associated with the systemic disease activity of AAV. METHODS: One hundred and four Chinese patients with AAV were recruited. Anti-plasminogen antibodies were detected in sequential serum samples at initial onset and remission of the disease. Associations of anti-plasminogen antibodies with clinicopathological parameters were analysed. RESULTS: The prevalence of anti-plasminogen antibodies was significantly higher in AAV patients than in healthy controls (19/104 vs 0/50, χ(2) = 8.8, P = 0.003). The prevalence of anti-plasminogen antibodies was significantly higher in the active stage of AAV than in remission (19/104 vs 1/48, χ(2) = 7.5, P = 0.013). The level of anti-plasminogen antibodies (expressed as a percentage of the positive controls) correlated with the ESR (r = 0.207, P = 0.042), serum creatinine (r = 0.302, P = 0.002), d-dimer (r = 0.273, P = 0.009) and the percentage of glomeruli with crescents in renal specimens (r = 0.393, P = 0.004). The level of Birmingham vasculitis activity scores and the prevalence of arthralgia and gastrointestinal involvement in patients with anti-plasminogen antibodies were significantly higher than in patients without anti-plasminogen antibodies [22.5 (s.d. 5.63) vs. 19.4 (s.d. 4.66), P = 0.015; 63.2% vs. 25.8%, P = 0.002; 57.9% vs. 21.1%, P = 0.001, respectively]. CONCLUSION: Circulating anti-plasminogen antibodies were associated with systemic disease activity and renal disease activity of AAV.

Epitope analysis of anti-myeloperoxidase antibodies in propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitis.

INTRODUCTION: Increasing evidence has suggested that linear epitopes of antineutrophil cytoplasmic antibody (ANCA) directed to myeloperoxidase (MPO) might provide clues to the pathogenesis of propylthiouracil (PTU)-induced ANCA-associated vasculitis (AAV). This study mapped epitopes of MPO-ANCA in sera from patients with PTU-induced MPO-ANCA (with or without vasculitis) and primary AAV, aiming to analyze certain epitopes associated with the development of PTU-induced AAV. METHODS: Six recombinant linear fragments, covering the whole amino acid sequence of a single chain of MPO, were produced from Escherichia coli. Sera from 17 patients with PTU-induced AAV, 17 patients with PTU-induced MPO-ANCA but without clinical evidence of vasculitis, and 64 patients with primary AAV were collected at presentation. Of the 17 patients with PTU-induced AAV, 12 also had sera at remission. The epitope specificities were detected by enzyme-linked immunosorbent assay by using the recombinant fragments as solid-phase ligands. RESULTS: Compared with patients with PTU-induced MPO-ANCA but without clinical vasculitis, sera from PTU-induced AAV patients showed significantly higher reactivity against the H1 fragment of MPO (optical density values: 0.17 (0.10 to 0.35) versus 0.10 (0.04 to 0.21), P = 0.038) and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.026). Compared with sera from primary AAV patients, sera from PTU-induced AAV patients had significantly higher reactivity to the P fragment and the H4 fragment (47.1% versus 14.1% P < 0.001; 41.2% versus 14.1%, P = 0.034, respectively), and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.013]. Among the 12 PTU-induced AAV patients with sequential samples, the number of fragments recognized in remission was significantly less than that in initial onset (two (none to four) versus none (none to 0.75), P < 0.001]. CONCLUSIONS: Linear epitopes of MPO molecules might be associated closely with PTU-induced AAV. In particular, the P and H4 fragments may be important epitopes in PTU-induced AAV.

Alternative complement pathway activation products in urine and kidneys of patients with ANCA-associated GN.

BACKGROUND AND OBJECTIVES: Previous study revealed that complement activation products of the alternative pathway could be detected in renal specimens of human ANCA-associated vasculitis. The current study aimed to investigate the clinical and pathologic significance of complement activation products in the urine and kidneys of patients with ANCA-associated vasculitis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal biopsy specimens from 29 patients with ANCA-associated vasculitis diagnosed at Peking University First Hospital from January of 2008 to December of 2010 were randomly collected. Urine samples from 27 of 29 patients in active stage and 22 ANCA-associated vasculitis patients in complete remission who were independent of the above-mentioned 29 patients were collected. Urine samples from 28 patients with lupus nephritis and 25 healthy individuals were also collected. The renal deposition of Bb, C3d, and C5b-9 were detected by immunohistochemistry. The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were determined by ELISA. RESULTS: The deposition, measured by the mean optical density of Bb, which is an alternative complement pathway marker, in glomeruli correlated with the proportion of total crescents (r=0.50, P=0.006), the extent of interstitial infiltrate (r=0.59, P=0.001), interstitial fibrosis (r=0.45, P=0.01), and tubular atrophy (r=0.55, P=0.002), whereas it correlated inversely with the proportion of normal glomeruli (r=-0.49, P=0.008). The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were all significantly higher in active compared with remission stage. The urinary levels of Bb in patients with active ANCA-associated vasculitis correlated with the serum creatinine (r=0.56, P=0.002) and correlated inversely with the proportion of normal glomeruli in renal specimens (r=-0.49, P=0.009). CONCLUSIONS: The present study provides additional evidence that complement activation through the alternative pathway occurred in the development of ANCA-associated vasculitis. The renal deposition of Bb and urinary Bb levels were associated with the severity of renal injury.

Epitope analysis of anti-myeloperoxidase antibodies in patients with ANCA-associated vasculitis.

OBJECTIVE: Increasing evidences have suggested the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCA) directing myeloperoxidase (MPO) in ANCA-associated vasculitis (AAV). The current study aimed to analyze the association between the linear epitopes of MPO-ANCA and clinicopathological features of patients with AAV. METHODS: Six recombinant linear fragments, covering the whole length amino acid sequence of a single chain of MPO, were produced from E.coli. Sera from 77 patients with AAV were collected at presentation. 13 out of the 77 patients had co-existence of serum anti-GBM antibodies. Ten patients also had sequential sera during follow up. The epitope specificities were detected by enzyme-linked immunosorbent assay using the recombinant fragments as solid phase ligands. RESULTS: Sera from 45 of the 77 (58.4%) patients with AAV showed a positive reaction to one or more linear fragments of the MPO chain. The Birmingham Vasculitis Activity Scores and the sera creatinine were significantly higher in patients with positive binding to the light chain fragment than that in patients without the binding. The epitopes recognized by MPO-ANCA from patients with co-existence of serum anti-GBM antibodies were mainly located in the N-terminus of the heavy chain. In 5 out of the 6 patients, whose sera in relapse recognize linear fragments, the reactivity to linear fragments in relapse was similar to that of initial onset. CONCLUSION: The epitope specificities of MPO-ANCA were associated with disease activity and some clinicopathological features in patients with ANCA-associated vasculitis.

Predictors for outcomes in patients with severe ANCA-associated glomerulonephritis who were dialysis-dependent at presentation: a study of 89 cases in a single Chinese center.

OBJECTIVE: Anti-neutrophilcytoplasmic autoantibody (ANCA)-associated vasculitis may cause rapid deterioration of renal function, resulting in high prevalence of end-stage renal disease and mortality. The current study investigated factors associated with restoration of renal function and early mortality in patients with severe ANCA-associated glomerulonephritis, i.e. dialysis-dependent at presentation, in a single Chinese cohort. METHODS: Eighty-nine Chinese patients with ANCA-associated glomerulonephritis who were on dialysis at the time of diagnosis were included in this study. All these patients received immunosuppressive therapy plus intravenous methylprednisolone, plasma exchange, or both. The predictive value of the clinical and histological parameters for renal and patient outcome was analyzed. RESULT: On the sixth month, 25 (28.1%) patients achieved dialysis independence, 45 (50.6%) patients progressed to end stage renal disease, and 19 (21.3%) patients died. Nine out of the 19 deaths were therapy-related. Factors independently associated with renal function restoration were percentages of normal glomeruli (P<0.05), extent of tubular atrophy (P<0.05) and extent of interstitial fibrosis (P<0.05) in the renal specimens. Age and pulmonary hemorrhage were independently associated with all-cause death (P=0.003 and P=0.007, respectively) and therapy-related death (P=0.037 and P=0.043, respectively). CONCLUSIONS: Among patients with severe ANCA-associated glomerulonephritis who were dialysis-dependent at presentation, those with a higher percentage of normal glomeruli and less extent of tubular atrophy/interstitial fibrosis have more chance of restoration of renal function. Increased risk for all-cause death and therapy-related death appears to be older age and pulmonary hemorrhage.

Association of circulating level of high mobility group box 1 with disease activity in antineutrophil cytoplasmic autoantibody-associated vasculitis.

OBJECTIVE: High mobility group box 1 (HMGB-1), a kind of proinflammatory mediator, is associated with inflammatory conditions and tissue damage. Previous studies have reported that circulating HMGB-1 levels in patients with active antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) were associated with renal manifestations and burdens of granulomatous inflammation. The current study aimed to investigate whether circulating HMGB-1 levels were associated with disease activity in AAV. METHODS: Plasma samples from 74 patients with AAV in active stage and 65 patients with AAV in remission were collected. The plasma levels of HMGB-1 were determined by enzyme-linked immunosorbent assay. Associations between plasma levels of HMGB-1 with clinical and pathologic parameters were analyzed. RESULTS: Plasma levels of HMGB-1 in active AAV patients were significantly higher than those in normal controls and AAV patients in remission (median 6.11 [interquartile range (IQR) 3.25-12.79] ng/ml versus median 1.12 [IQR 0.53-1.39] ng/ml, P< 0.001; median 6.11 [IQR 3.25-12.79] ng/ml versus median 3.04 [IQR 1.97-4.63] ng/ml, P < 0.001, respectively). Correlation analysis showed that plasma levels of HMGB-1 correlated with initial serum creatinine (r = 0.275, P = 0.018), estimated glomerular filtration rate (r = -0.277, P = 0.017), the Birmingham Vasculitis Activity Score (r = 0.308, P = 0.008), and C-reactive protein level (r = 0.309, P = 0.008). Among the patients with myeloperoxidase (MPO)-ANCA, those within the first quartile of plasma HMGB-1 levels had a significantly lower level of MPO-ANCA than those within the other 3 quartiles. CONCLUSION: Circulating HMGB-1 levels might reflect the disease activity and renal involvement of AAV vasculitis.

Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Studies in animal models suggest that complement activation is crucial in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Here we investigate the circulating complement activation profile of 66 patients with active stage AAV compared to that of 54 patients with AAV in remission. Plasma levels of C3a, C5a, soluble C5b-9, and Bb, all determined by enzyme-linked immunosorbent assay, were significantly higher in active stage than in remission of AAV, while plasma levels of properdin were significantly lower in the former than the latter disease stage. There was no significant difference in the plasma levels of C4d between active stage and remission. The plasma level of Bb in patients with active AAV significantly correlated with the proportion of total and cellular crescents in the renal biopsy, the erythrocyte sedimentation rate, and the Birmingham Vasculitis Activity Scores. Thus, systemic activation of complement by the alternative pathway takes place in human AAV. Circulating Bb might be a useful biomarker in assessing disease activity of AAV.