[98] This might be of relevance to recent studies that have found

[98] This might be of relevance to recent studies that have found increased glycoprotein B7-1 to nephrin mRNA ratios PI3K Inhibitor Library high throughput in urinary sediments from patients with minimal change disease compared with FSGS[99] and to the finding that urinary granzyme A mRNA levels can potentially distinguish patients with cellular rejection from those with AKI.[100] Harnessing

exosomal delivery mechanisms to therapeutic ends could have far-reaching consequences. The exploitation of ‘custom-made’ exosomes as a delivery tool for pharmacological agents could allow the precise targeting of those molecules to certain cell types. Exosomes are potentially ideal gene delivery vectors. Their small size and flexibility enables them to cross biological membranes, while their bi-lipid structure protects the mRNA, miRNA and protein cargo from degradation, facilitating delivery to its target. A proof of concept study has used modified

murine exosomes to successfully deliver siRNA resulting in gene-specific silencing in the brain.[101] For many kidney-related diseases a prime target for potential exosome-based therapy could be endothelial cells, which have essential roles in regulation of blood pressure, Opaganib clinical trial local regulation of blood flow, regulation of thrombosis and clearance of plasma lipids and are easily accessible to exosomes from the circulation. The artificial engineering of exosomes is a natural extension of the success of some liposomal therapies and can be used for delivery of specific RNAi molecules.[101] Furthermore, the purification and use of exosomes from particular cells or generated under certain stresses may be useful therapeutically. An example of this has developed from the interest in the mechanism underlying the potential of mesenchymal stem cells to promote tissue

repair and mediate check regeneration. Several studies have demonstrated that mesenchymal stem cells have the capacity to reverse acute and chronic kidney injury in different experimental models. These effects appear to be at least in part paracrine and can be largely mediated by the RNA cargo of exosomes and/or microvesicles.[102, 103] A potential approach to cancer immunotherapy based on exosomes has arisen from initial studies showing that dendritic cell-derived exosomes loaded with tumour peptides are capable of priming cytotoxic T cells. This can then mediate the rejection of tumours expressing the relevant antigens in mice.[104] These exosomes also promote natural killer (NK) cell activation in immunocompetent mice and NK cell-dependent anti-tumour effects. Based on these results, clinical trials are in progress. Vaccination strategies could also be envisioned using exosomes from tumour cells that carry tumour antigens.

We found that CXCL2 effectively restored neutrophil infiltration

We found that CXCL2 effectively restored neutrophil infiltration into the inoculated corneas and caused typical CaK in nude mice (Fig. 7). In fact, coadministration

of CXCL2 with blastospores exacerbated the severity of CaK and neutrophil infiltration in the corneas of BALB/c mice (Fig. 7). We compared the effect of IL-17 neutralization in mice concurrently inoculated with Candida in ear skin and the cornea. Contrary to its effect in cornea, IL-17 neutralization worsened the infection in skin (Fig. 8A). Histological analysis revealed www.selleckchem.com/products/ensartinib-x-396.html that while IL-17 neutralization inhibited leukocytes infiltration at both sites, it led to fungal expansion in the skin (Fig. 8B and C). These results suggest that IL-17 inhibition elicits protective

and destructive responses in corneas and skin, respectively. The pathogenic role of lymphocytes in infectious keratitis has been previously reported in experimental models of other pathogens. Over three decades ago, it was noted that nude mice did not develop viral keratitis when challenged with the herpes INCB024360 simplex virus [23]. Pearlman et al. showed that immunocompetent mice no longer developed Onchocerca volvulus keratitis when depleted of CD4+ cells [24]. By studying related mechanisms, Rouse and colleagues identified bystander activation of lymphocytes in the pathogenesis of herpes simplex keratitis [25, 26]. We report, for the first time, that CaK cannot be induced in either nude mice or CD4+ T-cell-depleted BALB/c mice, and that IL-17 is a critical factor in CaK initiation. We further showed that neutrophils and CD4+ T cells (supposed Th17 cells) are the main producers of IL-17

during CaK initiation (Fig. 4 and 5). On the other hand, Treg cells PJ34 HCl and γδ T cells, which are key players in other systems [27, 28], were not involved in CaK formation in cornea (Supporting Information Fig. 2). Though the differential roles of these cell types in CaK and herpes simplex keratitis could be explained by the significant difference in the properties of the two pathogens, more extensive studies are needed to investigate why Treg cells and γδ T cells are not seemingly involved in pathogenesis of FK. Lastly, the differential effects of IL-17 neutralization on CaK and fungal dermatitis in the same mouse (Fig. 8) underscore the duality of IL-17 activity and the importance of cellular context in the pathogenesis of keratitis [29-33]. Thus, the effects of C. albicans may not be recapitulated by other fungal genera. While highlighting a critical role for IL-17 in CaK initiation, our results also bring to light several intriguing questions concerning corneal infections. The first involves the mechanism of efficient fungal clearance in corneas of nude mice. It has been proposed that structural features, as well as some innate factors, afford corneas the ability to hinder pathogens [34] or blastospore-pseudohypha transformation [35].

This could be due to the binding

This could be due to the binding PLX-4720 cell line of NKp46 mAbs used for sorting and which increased the degranulation of NK cells compared with negatively sorted NK-cell subsets (data not shown). However, we did not detect “all-or-none” responses in the two murine NK-cell subsets.

NK cells from all subsets have overlapping functional characteristics, and it was reported in humans and mice that, e.g. IFN-γ production can change over a short period of time 29, 30. This demonstrates the variability of NK-cell functions. In conclusion, our data suggest the applicability of the surface marker CXCR3 for a better discrimination of murine NK-cell subsets resembling those in humans. Characteristics of the discussed NK-cell subsets are summarized in Fig. 7. This will form the basis for in vivo analyses of defined NK-cell subsets in animal models. The differential coexpression patterns of markers such as CXCR3 and CD27 on NK cells enables a more detailed characterization of NK-cell populations and indicates that the entire NK-cell compartment is composed of more than just the two subsets, which have been the focus of recent NK-cell research. For all experiments, 8–16 wk-old female C57BL/6 mice

(Charles River Laboratories, Wilmongton, BIBW2992 MA, USA and animal facility Hannover Medical School, Hannover, Germany) were used. Mice were bred under specific pathogen-free conditions and maintained in filter-topped cages under conventional conditions. Experiments involving animals were performed in compliance with federal and institutional guidelines (according to FELASA). Peripheral blood was taken from the retro orbital plexus and collected into heparinized tubes. White blood cells were prepared by hypotonic lysis of red blood cells (RBC lysis buffer, containing

NH4Cl) and washed in PBS containing 3% FCS (PAA Lab, Cölbe, Germany). Mice were selleck chemical euthanized by CO2 asphyxiation or cervical dislocation. Organs (LN, spleen, uterus, thymus, liver and lung) were extracted, sliced and homogenized with a 40 μm nylon (BD Pharmingen, Heidelberg, Germany) or steel mesh. For isolation of BM cells, femurs and tibiae were flushed with PBS using a 27G syringe. When necessary, cell suspensions were enriched for lymphocytes via density gradient (Lympholyte M, Cedarlane, ON, Canada) or treated with red blood cell lysis buffer (0.146 M NH4Cl, 0.1 mM EDTA-Na2, 1g NaHCO3, pH 7.3). The mouse-specific mAb Ly49D (4E5, FITC), Ly49G2 (4D11, FITC), Ly49C/I (5E6, FITC), NK1.1 (PK136, FITC, PE, APC), CD3 (145-2C11, FITC, PE, PerCP), CD16 (2.4G2, PE), CD27 (LG.3A10, PE), CD45 (30-F11, FITC, PerCP), CD107a (1D4B, FITC), CD122 (TM-β1, PE) and IFN-γ (XMG1.2, PE) were purchased from BD Biosciences (Heidelberg, Germany). In addition, the following mAb were used: CD3 (145-2C11, AlexaFluor® 647), CD27 (LG.3A10, PerCP/Cy5.5, Biolegend, San Diego, CA, USA), CD11b (M1/70.

Thus, the removal of monoubiquitinated Hrs from endosomal membran

Thus, the removal of monoubiquitinated Hrs from endosomal membrane could facilitate the clearance of the nonfunctional adapter and its replacement with nonubiquitinated and sorting-competent Hrs, as recently proposed in the case of growth factor receptors [28]. However, while in the same system Hrs is subjected to ubiquitin-dependent degradation, upon FcεRI engagement we have not detected any significant reduction in Hrs protein level consistent with the absence of polyubiquitinated Hrs species. Thus,

in our system Hrs ubiquitination would mainly serve to relocate buy Z-VAD-FMK Hrs from endosomes to the cytosol. All together our findings are compatible with the following scenario: upon antigen stimulation

ubiquitinated selleck chemicals FcεRI complexes are recognized by Hrs that becomes a substrate for Syk and Cbl enzymatic activities. We did not address the order in which Hrs phosphorylation and ubiquitination occur; however it is likely that Syk-induced Hrs phosphorylation occurs at the endosomal membrane and precedes Hrs ubiquitination. Monoubiquitinated Hrs is then removed from endosomal sorting sites allowing its replacement with non-ubiquitinated Hrs that may need to be tyrosine phosphorylated to interact with other endocytic adapters in order to ensure an efficient transport of ubiquitinated cargos. In this scenario, Hrs monoubiquitination would serve to relocate Hrs from endosomes to the cytosol, without promoting degradative events. Although additional experiments are required to Selleck Hydroxychloroquine validate our model, we demonstrate for the first time that engagement of an IR, namely FcεRI, has the potential to trigger Hrs phosphorylation and monoubiquitination, and that both inducible modifications require Syk kinase activity. From a broader cell biological perspective, this finding could be extended to include other IRs, such as the TCR and BCR, providing a novel regulatory mechanism used by the Syk family kinases to attenuate immune responses in mammalian

cells. The anti-FcεRI β subunit mAb (JRK) was kindly provided by Dr. J.-P. Kinet (Beth Israel Deaconess Medical Center, Boston, MA, USA). The anti-FcεRI γ subunit polyclonal Ab and the anti-pTyr 4G10 mAb were from UBI (Lake Placid, NY). Rabbit anti-Syk (N-19 and C-20), anti-Hrs (M-79), anti-Cbl (C-15) Abs, and anti-Hrs (D-3 and C-7) mAbs were from Santa Cruz Biotechnology (Santa Cruz, CA). Anti-phospho 334 Hrs Ab was from Assay Biotech (San Francisco, CA). Anti-DNP-specific mouse IgE (clone SPE-7), anti-actin (AC-15), and anti-β tubulin (Tub2.1) mAbs and all chemicals were from Sigma-Aldrich (Milan, Italy). The anti-Ub FK2 and FK1 mAbs were from Enzo Life Sciences (Exeter, United Kingdom). Lyso-Tracker Red was from Molecular Probes (Eugene, OR, USA). Purified and FITC-conjugated rat anti-IgE mAbs were from BD Biosciences (San Jose, CA, USA).

As shown in Figure 2B for three representative donors, binding of

As shown in Figure 2B for three representative donors, binding of the anti-NeuGcGM3 positive responders was not affected after trypsin treatment of L1210 cell surfaces. In contrast, binding was diminished in contrast to L1210 cell binding when the sera were incubated with L1210 cmah-kd cells. However, there is some degree of recognition of the L1210 cmah-kd cell line, presumably due to binding of the serum polyclonal antibodies to non-NeuGc-related antigens. No binding was detected against normal human PBMCs. Moreover, pretreatment of the positive sera with NeuGcGM3

but not with NeuAcGM3 strongly affected the percentage of L1210 stained cells (Fig. 2C). JQ1 purchase In concordance with the results obtained by ELISA, the percentage of tumor cells recognized by the healthy donors’ sera significantly decreased with increasing donor age (Fig. 2D). Also, the number of the healthy donors with serum containing antibodies able to recognize L1210 cell line decreased with age (Fig. 2E). Next, we tested whether the anti-NeuGcGM3 antibodies present in healthy human sera CT99021 research buy were able not only to recognize but also to induce the death of L1210 cells. Forty healthy donors’ samples, with positive binding to NeuGcGM3 by ELISA and to L1210 by flow cytometry, were incubated for 4 h at 37°C with L1210 cells,

and cell death was detected by PI incorporation. Thirty-five of the sera tested induced complement-mediated cell death of L1210 cells (Supporting Information Fig. 4). The anti-NeuGcGM3 mAb 14F7 and antibodies against Celastrol this antigen induced in NSCLC patients treated with the 1E10 anti-idiotypic vaccine are able to kill tumor cells by a complement-independent

mechanism [18, 20]. In order to test whether the anti-NeuGcGM3 antibodies present in healthy human sera share this property, the samples were heated at 56°C for 30 min to inactivate complement before evaluating their cytotoxic capacity. Interestingly, 11 out of 35 donors’ sera that induced complement-mediated cell death still showed cytotoxic capacity after complement inactivation (Fig. 3A). There was a positive correlation between the complement-independent cytotoxicity capacity and both the levels of anti-NeuGcGM3 antibodies measured by ELISA and tumor cell binding by flow cytometry (Supporting Information Fig. 5). Furthermore, ten of these 11 donors were less than 30 years of age. In order to define whether the anti-NeuGcGM3 anti-bodies present in normal human sera mediate this complement-independent cytotoxic effect, we evaluated cell death in tumor cell lines that express or do not express the NeuGcGM3 ganglioside. As shown in Figure 3B for three healthy donors, sera that induced the death of L1210 cells lacked this activity against malignant cells that do not express NeuGcGM3 ganglioside.

These data suggest that mediators synthesized by the pathogen dur

These data suggest that mediators synthesized by the pathogen during infection regulate both protective as well as detrimental responses

to the host. Thus, discovery and characterization of Mtb-secreted proteins could be an approach to identify novel therapeutic and diagnosis targets as well as biomarkers of disease. Lectins are classically defined as a family of proteins with the ability to specifically bind carbohydrate moieties. A number of pathogens have been demonstrated to express GPCR Compound Library manufacturer such molecules, which are involved in recognition and invasion processes 17, 18. For example, Pseudomonas aeruginosa produces several membrane-associated lectins that promote attachment to epithelial cells and contribute to its virulence 19. In addition, bacterial lectins could be released into the extracellular milieu and play an important role during infection as demonstrated by experiments using Bordetella18. These data suggest that both membrane-expressed and secreted lectins participate in host–microbial interactions. In the case of Mtb, the heparin-binding hemagglutinin adhesin (HBHA) is one of the most studied cell surface-expressed lectins

and it has been shown to be critical for bacterial dissemination in vivo20. Moreover, the existence of at least 11 hypothetical lectins from Mtb21 suggests that these molecules may be an important component of the host–mycobacteria interplay. Consistent with this, Trichostatin A nmr Sitaxentan active TB (ATB) patients have been found to display increased levels

of anti-HBHA Ab during active disease 22, 23, suggesting that mycobacterial lectins may elicit specific immune responses. We have utilized a previously generated non-redundant lectin data bank 24 in order to identify lectins from Mtb, a major human pathogen. In the present study, we have demonstrated a secreted 13 kDa ricin-like lectin from Mtb (sMTL-13). sMTL-13 was detected in pleural biopsies from ATB patients and led to an increased IFN-γ production by PBMC from patients during active disease. Importantly, ATB patients display high titers of serum IgG against sMTL-13, a response found to be rapidly decreased following successful treatment. These data report a secreted Mtb lectin with antigenic activity in human TB and suggest it may be useful as a biomarker of disease therapy. We have previously generated a non-redundant lectin database for searching lectin domains from Arabidopsis thaliana genome 24. To further evaluate the presence of such domains in an important human pathogen, Mtb, we have adapted this database and identified a single hypothetical lectin encoded by the Rv1419 gene. Figure 1A shows the bioinformatics characterization of the Rv1419 gene. Its open reading frame (ORF) contains 474 nucleotides and the aa sequence encodes a hypothetical protein of 157 residues containing a signal peptide and a predicted molecular mass of 16.8 kDa.

Protein modified diets of all types lasting a minimum of 4 months

Protein modified diets of all types lasting a minimum of 4 months were considered

with protein intake ranging from 0.3 to 0.8 g/kg per day. Overall protein restriction appeared to slow progression of CKD, but not by much on average. Individual variability suggests some may benefit more than others. Results of meta analysis imply that patients can delay dialysis by, on average around one or 2 months. Positive selleck chemical but non-significant correlation between improvement in GFR and level of protein restriction is evident. There were insufficient studies to recommend a level of protein intake. Furthermore, problems of non-compliance remain a significant issue. The review also considered different sources of protein (e.g. red meat, chicken, fish, vegetarian); however, relevant studies are of short duration only. The authors consider that the available information supports further research in this area. The number of studies that include people with type 2 diabetes are limited. The study by Dussol et al.121 was the only other RCT identified that was not reviewed by Robertson et al.120 This 2 year single centre RCT of type 1 and type

2 diabetes indicated that the low-protein diet did not alter the course of GFR or of AER in people with diabetes with incipient or overt nephropathy. Table A6 includes a summary of studies identified by the search strategy. The studies are characterized

by being small and of short duration. Relevant details are provided selleck below; however, as for dietary fat, there are insufficient reliable studies that provide evidence to support a recommendation in relation protein restriction in the prevention and management 3-oxoacyl-(acyl-carrier-protein) reductase of CKD in people with type 2 diabetes. When considering the evidence related to salt intake and CKD in people with type 2 diabetes, the following points made based on a literature review for preparation of a Cochrane Protocol are noteworthy:122 Dietary salt is important in BP control in both hypertensives and normotensives (supported by meta-analyses) and therefore expect that this could be protective in the development and progression of CKD. Table A7 presents a summary of studies identified by the search strategy in relation to the assessment of the role of restricted salt intake. As for protein restriction the studies are small and of short duration. Details of the studies are included in Table A7; however, it is concluded that there are insufficient reliable studies that provide evidence to support a recommendation in relation to restriction of dietary salt and the prevention and management of CKD in people with type 2 diabetes. Smoking increases the risk of the development and progression of CKD in people with type 2 diabetes (Evidence Level II – Aetiology).

pylori detected in the stomach

The challenge procedure i

pylori detected in the stomach.

The challenge procedure is relatively well established in the literature, but its efficiency varies at different institutions and is mainly dependent on the infecting strain utilized. In our laboratory, the H. pylori challenge has been effective in inducing infection in ∼80% of mice. Infected mice tended to have either a high number (∼1 × 104) of H. pylori copies μg−1 DNA – which likely indicates no protection as that was the level shown by unvaccinated mice – or a low number (∼1 × 102.5× 104) selleckchem of H. pylori copies μg−1 DNA – which likely indicates partial protection. The challenge method utilizes a high dose (1 × 109) of H. pylori organisms over a brief period, which is unlike natural human infection that occurs through exposure to low levels of H. pylori over a prolonged period. This artificial way of Panobinostat manufacturer infection may partially explain why some properly immunized mice missed protection. We could not find a good serological correlate of protection. Even though as a group, those with the highest serum IgG and IgA had the lowest geometric mean H. pylori copies μg−1 DNA, the correlation

was very poor at the individual level (r2=0.3037 and 0.0577 for IgG and IgA, respectively). This finding suggests that serum antibodies are markers of immune response but, by themselves, play a limited role in protection, and that other arms of the immune system (innate, cellular, mucosal) are more important. Unfortunately, in this set of experiments, we could not detect any stool antibodies. We expressed the level of infection as the number of H. pylori copies μg−1 purified DNA. This is unconventional as most studies express the level of infection as H. pylori copies mg−1 Nintedanib (BIBF 1120) of stomach. We decided to use DNA as the denominator because our detection method was based on PCR

of purified DNA and the purification efficiency may have varied for each specimen. Indeed, even though there was a good correlation between the weight of the stomach and the amount of DNA purified, it was less than perfect (r2=0.59). So that our results can be compared with the ones reported in other studies, in our experiments, on average, 3.4 H. pylori copies μg−1 DNA corresponded to 1 copy mg−1 stomach. In conclusion, our study adds to the evidence that rUreB is a promising H. pylori vaccine candidate, that aluminum hydroxide has a significant but modest adjuvant effect and that better adjuvants must be pursued. This work was partially funded by NIH grant R03CA128048. The authors have no competing interests. “
“Mammalian TLRs in adult animals serve indispensable functions in establishing innate and adaptive immunity and contributing to the homeostasis of surrounding tissues. However, the expression and function of TLRs during mammalian embryonic development has not been studied so far. Here, we show that CD45+ CD11b+ F4/80+ macrophages from 10.5-day embryo (E10.5) co-express TLRs and CD14.

In A  fumigatus, DNA smearing was found after treatment with H2O2

In A. fumigatus, DNA smearing was found after treatment with H2O2 and AmB as well as in A. nidulans after treatment with phytosphingosine.[22, Ruxolitinib order 23] DNA smearing rather than a ladder was demonstrated by agarose electrophoresis in R. arrhizus after treatment with H2O2 and AmB. The apoptotic-like phenotype of R. arrhizus was also indentified using the TUNEL assay, which is more sensitive than DNA agarose electrophoresis for analysing apoptotic DNA fragmentation. Microscopic images revealed the presence of significant green fluorescence in the cells treated by high but non-fungicidal concentrations of the two triggers,

but minimal fluorescence was seen under low concentrations. These phenomena were also reported in many other fungi, such as S. cerevisiae treated with H2O2 and acetic acid, C. albicans treated with farnesol, A. fumigatus treated with H2O2 and AmB and A. fumigatus in the stationary phase.[7, 9, 23, 24] DHR123/PI double-staining by flow cytometry can better explain the change of apoptotic or dead cells. In our study, an apoptotic phenotype can be induced by low but toxic concentrations of both triggers through ROS accumulation

within cells, whereas dead cells stained with PI increased after treatment with high concentrations of the triggers. These findings indicate that treatment with low concentrations of both triggers can induce an apoptotic-like phenotype through ROS accumulation and ultimately cause death under

continued accumulation with increased PI-positive staining. It is well known that ROS plays a major role in signalling Selleckchem IDH inhibitor and/or effector functions in apoptosis.[25] The production of ROS in apoptotic cells has been examined in other fungal cells, including C. albicans, S. cerevisiae and A. nidulans.[18, 26, 27] ROS accumulation has also been demonstrated in many fungal and mammalian cells and played a central role in the induction of apoptosis.[6, 7, 28] This study indicated that both H2O2 and AMB could induce the apoptotic-like phenotype in R. arrhizus, which might be usefully exploited in the search for and design of novel therapies in the future. This work was supported by National Natural Science Foundation (81371783) from the National Natural Science Foundation of China. The authors report no conflicts of interest. The authors alone are responsible for Ketotifen the content and writing of the paper. “
“The combination of amphotericin B and sodium deoxycholate is the formulation most used in clinical practice. The development of new agents such as amphotericin with lipid formulations, caspofungin, voriconazole and other azolic derivatives, promoted alternatives to amphotericin B deoxycholate. However, because of the high cost of these new drugs, their use is difficult in a scenario of limited resources. A few strategies have been devised to make the use of amphotericin B deoxycholate less toxic.

Fourteen patients (64%) with kidney involvement achieved remissio

Fourteen patients (64%) with kidney involvement achieved remission, and in seven patients (50%), no flare was seen during the follow-up period. Three patients had renal flare and were successfully re-treated with RTX. Seventeen patients had disease symptoms from airways and eyes at RTX initiation, whereas only 29% displayed ≥50% treatment response. Limited clinical improvement was seen in patients with endobronchial lesions and trachea-subglottic granulomatous disease. RTX is a potent therapeutic

option for ANCA-associated vasculitis refractory to conventional treatment. Best response may be expected in patients with vasculitic manifestations. Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis,

is a life-threatening systemic autoimmune vasculitis PD0325901 cell line characterized by a necrotizing, granulomatous inflammation that predominantly involves upper airways, lungs and kidneys. The disease involves see more small and medium-sized vessels and is frequently associated with antineutrophil cytoplasmic antibodies (ANCA) recognizing proteinase-3 (PR3). The presence of cytoplasmic ANCA is observed in the majority of patients with active disease, and ANCA titre correlates often with the severity of the disease and response to treatment [1]. In vitro, ANCA causes neutrophil activation, resulting in a respiratory burst and the release of inflammatory cytokines. In a mouse model, the transfer of ANCA specific for MPO causes crescentic glomerulonephritis and small-vessel vasculitis [2], suggesting that ANCA-producing B cells may be directly involved in the disease pathogenesis as precursors of plasma cells producing ANCA [1, 3, 4]. Untreated, the disease usually progresses from a limited necrotizing granulomatous process Paclitaxel to a generalized vasculitis and leads

to fatal outcome in >90% of patients in 2 years with mean survival time of 5 months [5]. The advent of cyclophosphamide (CYC) therapy together with corticosteroids for the induction of remission has reduced the mortality greatly and has become a conventional treatment option of GPA. Although this therapy remains the most effective initial treatment for the active disease, this regimen is associated with toxicity, increased rate of severe infections and dose-related increases in rates of haematological and solid organ malignancies [6]. For this reason, several other immunosuppressive agents, including methotrexate, azathioprine, mycophenolate mofetil, have been used to maintain remission. Unfortunately, in up to 10% of patients, disease is refractory to conventional therapy [7]. Rituximab (RTX) is a chimeric monoclonal antibody directed against the CD20 antigen found on the surface of B lymphocytes. It induces 98% depletion of peripheral blood B cells, but only 40–70% of lymph node B cells are depleted [3].