[9] A necrotic eschar in maxillary, facial, or sino-orbital mucosal surfaces in an immunocompromised host may be an early this website sentinel marker of invasive

mucormycosis. Pleuritic pain in a neutropenic host also may signify an angioinvasive filamentous fungus. Pleuritic pain in a neutropenic or HSCT patient receiving voriconazole prophylaxis has a high probability of being invasive mucormycosis instead of aspergillosis. Diplopia is an early manifestation of sino-orbital mucormycosis in a diabetic patient that usually signifies involvement of the extraocular muscles or their innervating nerves.[10] Hyperglycaemia in diabetic patients may produce blurring of vision, but does not produce diplopia. During sino-orbital mucormycosis, hyphae involving the ethmoid sinus breach the lamina papyracea to invade the medial rectus muscle creating dysconjugate vision. The organism may extend along the emissary veins to the ethmoid sinus to the cavernous sinus and encroach upon the critical cranial nerves involve III, IV, V (1, 2) and VI. Diplopia in a diabetic patient or other compromised host with ethmoidal sinusitis should be assessed aggressively for sino-orbital mucormycosis. Necrotic cutaneous lesions in immunocompromised

patients may also be caused by mucormycosis. The differential diagnosis includes Enzalutamide clinical trial other angioinvasive pathogens including Aspergillus, Fusarium, Pseudallescheria, Scedosporium species. Pseudomonas aeruginosa and occasionally members of Enterobacteriaceae in the same host also cause ecthyma gangrenosum. The preponderance

of cases of cutaneous mucormycosis is associated with direct inoculation rather than haematogenous dissemination.[1] Characteristic hyphal structures are seen on biopsy MTMR9 and wet mount of tissue. Earlier recognition of sinus and pulmonary lesions by CT scanning is an important advance over conventional sinus and chest radiographs. Early CT findings may reveal pulmonary or sinus lesions before localising symptoms in immunocompromised patients who are at high risk for invasive sino-pulmonary mucormycosis. Among the lesions associated with angioinvasive filamentous fungi are nodules, halo signs, reverse halo signs, cavities, wedge-shaped infiltrates and pleural effusions associated with pleuritic pain.[11] Among these lesions, the reverse halo sign in the neutropenic patient has high predictive value for mucormycosis.[12] Early recognition of risk factors, clinical manifestations and diagnostic imaging findings may increase the probability of an early recognition and lead logically to a definitive diagnosis by culture and biopsy of tissue or the use of novel molecular and antigenic assays.

For example, activation of iNKT cells by administration of α-GalCer has been shown to protect against autoimmune diseases in IL-4- or IL-10-deficient mice.106,107 It has also been demonstrated that iNKT cells can prevent type I diabetes without driving a

Th2 shift in autopathogenic T cells.108 Thus, attention has focused on the role of iNKT cells in the induction of tolerizing or non-inflammatory NVP-BGJ398 DCs. At least three different pathways have been identified by which iNKT cells may promote the generation of regulatory DCs. These are illustrated in Fig. 2, and described in detail below. Repeated administration of cognate antigens can lead to an ‘exhaustion’ phenotype in MHC-restricted T cells, and a similar Ku-0059436 in vivo effect appears to occur for iNKT cells with α-GalCer (Fig. 2a): after multiple exposures to α-GalCer in vivo, iNKT cells develop a functionally anergic phenotype that is associated with expression of the inhibitory receptor programmed death (PD)-1.109 When iNKT cells become exhausted in this way, their interactions with DCs change and instead of promoting the maturation of pro-inflammatory

DCs, they induce a regulatory DC phenotype that is characterized by lower expression levels of CD80, CD86 and CD40, with reduced IL-12 and increased IL-10 secretion.110,111 In autoimmune disease models, regulatory DCs that are generated through this pathway prevent the onset of autoimmunity and silence autopathogenic T cells.91,111 It is difficult to fully gauge the effects of self antigen-activated iNKT cells on DC phenotype in vivo; however, in vitro studies have suggested that this pathway can provide a maturation stimulus to immature DCs, but that the resulting DC phenotype is a comparatively non-inflammatory one (Fig. 2b). Vincent et al.65 showed that, in contrast to DCs that matured in response to α-GalCer-stimulated iNKT cells, those that matured in response to self antigen-activated iNKT cells showed up-regulation

of costimulatory Idoxuridine molecules such as CD86 but produced more IL-10 than IL-12. These DCs efficiently promoted T-cell proliferation, but did not stimulate marked T-cell IFN-γ production.65 DCs are known to develop from haematopoietic stem cells via multiple distinct differentiation pathways. Some develop directly into precursor DCs in the bone marrow, which then enter the bloodstream and continuously renew immature DC populations within the tissues.112 Other myeloid DCs arise from progenitors that reside in the periphery. Monocytes constitute one such precursor population. Every day about one-third of the blood monocytes are estimated to leave the bloodstream and enter the tissues.113,114 There, they can remain monocytic, become macrophages, or become DCs. Thus, understanding the types of signals that determine their choice of fate is an area of great interest.

“
“Lipoastrocytoma is an extremely selleck chemicals llc rare tumor, with only six cases described. We report the case of an astrocytoma involving the upper part of the cerebellar-pontine angle and the right portion of the clivus starting from the brainstem with a diffuse lipomatous component in a 39 year-old man. The patient was admitted with headache of 1 year’s duration and diplopia over the previous 3 months. MRI revealed a ponto-cerebellar lesion that showed irregular enhancement

after contrast administration. Subtotal excision of the tumor was accomplished. Adjuvant chemotherapy and radiation therapy were not administered. Histologically the tumor showed the classical histology of low-grade astrocytoma and a portion of the lesion was composed of lipid-laden cells. Immunohistochemistry for glial fibrillary acid and S-100 proteins clearly demonstrated the glial nature of these cells. Ki-67/Mib-1 labeling index was low (2%). The patient ALK inhibitor cancer remains in good neurological conditions after 10 months. Our case has a benign postoperative behavior, also after subtotal excision, with restrictions due to the short follow-up. It is important

to record each new case of this rare tumor to produce a better characterization of this lesion. “
“I. Bodi, R. Selway, P. Bannister, L. Doey, N. Mullatti, R. Elwes and M. Honavar (2012) Neuropathology and Applied Neurobiology38, 411–425 Diffuse form of dysembryoplastic neuroepithelial tumour: the histological and immunohistochemical features of a distinct entity showing transition to dysembryoplastic neuroepithelial tumour and ganglioglioma Aims: A diffuse variant of dysembryoplastic neuroepithelial tumour (dDNT) has previously been described, which although composed of oligodendroglia-like cells (OLC), astrocytes and mature neurones, lacks the multinodularity and ‘specific component’ of typical DNT. The

dDNT poses a significant challenge to the neuropathologist. This study Amrubicin was undertaken to further characterize the histological and immunohistochemical features of dDNT. Materials and methods: Review of our archived material from epilepsy surgery identified 16 cases, in which features of dDNT predominated. Their histological and immunohistochemical features, including CD34 and nestin immunohistochemistry, were analysed. Results: Seven cases had the characteristics of pure dDNT. A further two cases of dDNT showed extension into the white matter with occasional dysplastic neurones. Two additional cases had similar features but with the presence of either single, or multiple small nodular clusters of OLC, in keeping with transition to classical DNT. Five cases showed ganglioglioma-like areas, of which three cases had micronodule formation but with predominant dDNT pattern.

Candida albicans was the predominant yeast isolated [30 patients (62.5%)], followed by C. parapsilosis [6 (12.5%)] and C. dubliniensis 5 (10.4%). Aspergillus fumigatus was the most common filamentous fungus [5 (10.4%)] and non-fumigatus Aspergillus species were isolated from four (8.3%) patients. Staphylococcus aureus was the most frequently detected bacterium in C. click here albicans

positive samples (53.57%). A. fumigatus and Pseudomonas aeruginosa or S. aureus were detected together in 75% of A. fumigatus positive samples each. No statistically significant relationship was detected between growth of yeast and moulds and age, gender, the use of inhaled corticosteroids or tobramycin. No significant correlation was found between the isolation of C. albicans, A. fumigatus and P. aeruginosa, Stenotrophomonas maltophilia Selleckchem Dasatinib or S. aureus, and the isolation of C. albicans and Haemophilus influenzae. Other factors which may be responsible for the increased isolation of fungi in CF need to be investigated. “
“Patients with acute myelogenous leukaemia (AML) and neutropenia after chemotherapy are at high risk for life-threatening invasive fungal disease (IFD), in particular, invasive aspergillosis (IA). The aim of the study was to evaluate data on characteristics, risk factors, complications and additional

antifungal treatment of patients with AML receiving posaconazole prophylaxis (PP) after chemotherapy in an actual clinical setting. A retrospective single-centre observational study on 40 patients with AML, median age 66 years, was conducted. PP 200 mg three times daily was given routinely. After 76 cycles of remission induction chemotherapy followed by PP, median duration of 31 days (range 6–61 days), no fatal case occurred. Metalloexopeptidase The majority of patients had at least one additional risk factor for IFD and during 32 cycles (42.1%), three risk factors were present. During 40 therapy cycles (52.6%), fever of unknown origin occurred. Pneumonia was diagnosed after 23 cycles

(30.3%), thereof one case of proven IA (1.3%). PP was interrupted in 25 cycles (32.9%) and was followed by systemic antifungal therapy with different agents, with a median duration 15 days (range: 6–32 days). PP appears to be an effective and well-tolerated protection against IFD for AML patients under natural clinical conditions. “
“Data on the epidemiology of invasive Candida infections in paediatric patients in Europe are still limited. The aim of this retrospective study was to analyse the epidemiology of candidaemia in a tertiary paediatric hospital in Poland from 2000 to 2010. Using microbiological records, a total of 118 episodes of candidaemia were identified in 114 children, with an annual incidence of 0.35 episodes/1000 discharges. The highest incidences were found in the medical intensive care unit (5.28), and in neonatal intensive care (1.47). The mortality rate was 8.5%. Candida albicans and C. parapsilosis were the most prevalent species (39.8% and 35.6% respectively).

CD137L/pSBSO and SB11 were co-transfected into K562 cells using Lipofectmin 2000 (Invitrogen, Carlsbad, CA, USA), according to the manufacturer’s instructions. The transfected K562 cells were cultured for 3

weeks, and then stained with FITC anti-human CD137L antibody. CD137L-positive K562 cells (CD137L-K562) were sorted by the fluorescence activated cell sorter (FACS)array II cytometer (BD Biosciences, San Jose, CA, USA) and continued to culture for another 2 weeks, then sorted again. After that, IL-21-Fc(CoOP)-pSBSO was transfected into CD137L-K562 cells together with SB11. Transfected CD137L-K562 cells were cultured for 3 weeks, and then stained with PE anti-human IL-21 antibody. IL-21-positive CD137L-K562 cells (mbIL-21-CD137L-K562) Selleckchem Lumacaftor HSP activation were sorted by the FACSarray II cytometer and continued to culture for another 2 weeks before sorted again. Human peripheral blood mononuclear cells (PBMC) were obtained from the Shanghai Blood Center

under a research protocol approved by the Department of Shanghai Blood Administration. PBMC were used either fresh or frozen in 10% dimethylsulphoxide (DMSO) containing fetal bovine serum (FBS). Frozen PBMC were thawed 1 day prior to the cultivation in RPMI-1640 medium supplemented with 10% fetal calf serum (FCS), 1% penicillin–streptomycin, 2 mM L-glutamine and 200 U/ml IL-2 in 5% CO2 at 37°C. MbIL-21-CD137L-K562 cells were pretreated with 15 μg/ml of mitomycin for 4 h and then washed twice with phosphate-buffered saline (PBS), mixed with PBMC at 2:1 and incubated in RPMI-1640 medium supplemented with 10% FCS, 1% penicillin–streptomycin, 2 mM L-glutamine and 100 U/ml IL-2 in 5% Sorafenib datasheet CO2 at 37°C. Repeated stimulation was performed weekly. For the STAT-3 inhibition experiment, JSI-124, a specific STAT-3 inhibitor, was added to a final concentration of 0·1 μM at the third stimulation, and DMSO was added as control. NK cell receptor expression, NK cell proliferation and cytotoxicity were analysed by flow cytometry, trypan blue staining and cytotoxicity assay at different time-points, respectively.

Cells were exposed to appropriate antibodies for 30 min at 4°C, washed and resuspended in PBS containing 1% FBS. Data were acquired using a FACSCalibur cytometer (BD Biosciences) and analysed using FlowJo software (Ashland, OR, USA). Human peripheral blood mononuclear cells and red blood cells (RBC) were obtained from Shanghai blood centre under a research protocol approved by the Department of Shanghai Blood Administration. NK cells were purified using the RosetteSep Human NK Cell Enrichment Cocktail (StemCell Technologies, Vancouver, BC, Canada), as described previously [7]. Briefly, 1 × 106 PBMC were mixed with 100 × 106 RBC before 1 μl RosetteSep reagent was added per 1 × 106 of PBMC.

Finally, FcR γ-chain-deficient mice are devoid of FcεRI and therefore any FcεRI-mediated effects of OVA-specific IgE during the sensitization or challenge phase, either due to mast-cell activation or altered DC function, is absent in these mice. Although the sensitization/challenge model that we used does not require B cells or antibodies, including

allergen-specific IgE, FcεRI, or mast cells 21, 22, it remains possible that in vivo FcεRI facilitated enhanced antigen-uptake or activation of pulmonary DC indirectly through mast-cell activation 23, 24. In contrast to previous studies 13, 14, 17 that employed BMDC and sensitization of FcγR-deficient mice, we aimed to specifically delineate the contribution Venetoclax of FcγR on lung DC during the challenge phase of the murine asthma model. We first confirmed the expression of FcγR expression on lung DC and compared their function to spleen-derived DC subpopulations, as the importance of considering the phenotypic, functional and anatomical differences of various DC subsets has been supported by several studies 25. Thus, our studies

focus on selleck chemicals llc DC populations obtained from lymphoid organs in addition to pulmonary DC to study the function of FcγR. This revealed that lung DC and splenic CD8− DC gave rise to increased CD4+ T lymphocyte stimulation when DC acquired antigen as immune complexes via FcγRI, FcγRIII or FcγRIV. This effect was absent when CD8+ DC or FcR γ-chain deficient DC were used. These observations would be consistent with the view that contamination Sucrase of OVA with endotoxins was not responsible for these alterations. Additional results support this interpretation. First, DC of TLR4-deficient mice led to increased T-cell proliferation after exposure to OVA-IC as compared to OVA alone. Second, serum of sensitized mice, which contained anti-OVA IgG, caused increased T-cell proliferation when given together with OVA to WT lung DC. This effect was antigen-specific, as serum of BSA-sensitized

mice did not cause this outcome, and FcγR-dependent, given that FcR γ-deficient DC did not result in increased T-cell proliferation. Several observations support the impact of FcγR on DC during the effector phase of pulmonary hypersensitivity. First, we adoptively transferred Th2-biased antigen-specific CD4+T lymphocytes 4 into antigen-naïve mice, thereby restricting the induction of pulmonary hypersensitivity mainly to the DC–T-cell interaction. Second, pulmonary exposure of mice to OVA-IC dramatically increased eosinophilia in the BALF and cellular infiltration in the lungs, an effect that was not observed in naive mice and thus not induced non-specifically. Third, the increased pulmonary immune reaction induced by OVA-IC was paralleled by a highly significant increase in proliferation of antigen-specific T cells, both in vitro as well as in vivo.

This may possibly be due to a shortened G1 phase caused by DPP2 kd, an observation that we made in DPP2 kd fibroblasts, which proliferate faster than WT cells in the presence of serum (unpublished result). Similarly, it has been reported that T cells lacking transactivator of ErbB2 (TOB1) have a reduced threshold of activation 34. Furthermore,

loss of Lung-Kruppel-like PLX4032 molecular weight factor 2 (KLF2) leads to a loss of quiescence defined by proliferation, increased metabolism and altered expression of activation markers 35. Interestingly, we previously demonstrated that DPP2 is transcriptionally activated by KLF2 and TOB1, linking them in a program that maintains lymphocyte quiescence, which is regulated by quiescence-specific transcription 3. Collectively, these data support the role of DPP2 in preventing proliferation and promoting quiescence. selleck chemicals Of particular interest is the finding that naïve T cells from lck-DPP2 kd mice mainly produce IL-17, the signature cytokine of Th17 cells 36, upon TCR-mediated activation in vitro. In addition, these cells significantly upregulate rorγt mRNA, the master

regulator of Th17 differentiation 15. In agreement with this observation, we found that IL-2 and IFN-γ production was downregulated in the activated mutant T cells. CD4+ and CD8+ T cells respectively, produce these cytokines after TCR activation in the absence of exogenous

factors. Furthermore, IL-2 has been shown to induce Foxp3 expression and inhibit Th17-cell differentiation 37. Collectively, our data support the notion that loss of DPP2 causes T cells to differentiate into Th17 cells and IL-17 producing CD8+ T cells upon TCR stimulation. It can be surmised from these results that the out production of the inflammatory cytokine IL-17 is the default pathway in T-cell differentiation and is actively suppressed by DPP2. Such a control may be important to prevent expansion of autoreactive T cells. In agreement with this hypothesis, we observed increased levels of ANA in the lck-DPP2 kd mice, indicative of augmented autoantibody production in these mice. Th17 cells have been implicated in numerous human diseases, such as psoriasis, rheumatoid arthritis, multiple sclerosis, asthma and some bacterial and fungal infections 38. A recent report on the effects of the loss of early growth response gene-2 in T cells suggests that autoimmune disorders can result from a loss of effector T-cell expansion and inflammatory activation 39. This is consistent with the observations made in lck-DPP2 kd mice, where T cells are hyper-proliferative and differentiate into IL-17-producing cells. Several other reports have also shown examples of proteins that act to prevent abnormal T-cell proliferation and autoimmunity associated with the production of IL-17.

The consistent above average home dialysis rates witnessed in New South Wales appear to be the result of renal unit culture, education strategies and policies that support ‘home dialysis first’. “
“Aim:  Hyperphosphataemia is almost inevitable in end stage renal disease (ESRD) patients and is associated with increased morbidity

and mortality. In this study we examined whether oral activated charcoal (oAC) reduces serum phosphate level in haemodialysis patients. Methods:  This was an open-label, prospective, uncontrolled study. One hundred and thirty-five haemodialysis patients were included in this study, with cessation of treatment with any phosphate binders during a 2 week washout period. Patients with serum phosphate levels greater than 5.5 mg/dL during the washout period were included for Hydroxychloroquine treatment with oAC. oAC was started at a dose of 600 mg three times per day with meals and was administered for 24 weeks. oAC dose was titrated up during the 24 week period to achieve phosphate control (3.5–5.5 mg/dL). A second 2 week washout period followed the end of oAC treatment. Results:  In the 114 patients who successfully completed the trial, the mean dose of activated charcoal was Palbociclib ic50 3190 ± 806 mg/day. oAC reduced

mean phosphate levels to below 5.5 mg/dL, with mean decreases of 2.60 ± 0.11 mg/dL (P < 0.01) and 103 (90.4%) of the patients reached the phosphate target. After the second washout period the phosphate levels increased to 7.50 ± 1.03 mg/dL (P < 0.01). Serum intact parathyroid hormone (iPTH) levels declined from 338.75 ± 147.77 pg/mL to 276.51 ± 127.82 pg/mL (P < 0.05) during the study. oAC had Cediranib (AZD2171) no influence on

serum prealbumin, total cholesterol, triglycerides, serum ferritin, haemoglobin or platelet levels and the levels of 1,25-dihydroxyvitamin D were stable during the study. Conclusion:  In this open-label uncontrolled study, oAC effectively controls hyperphosphataemia and hyperparathyroidism in haemodialysis patients. The safety and efficacy of oAC needs to be assessed in a randomized controlled trial. “
“Currently available calcium and aluminium based phosphate binders are dose limited because of potential toxicity, and newer proprietary phosphate binders are expensive. We examined phosphate-binding effects of the bile acid sequestrant colestipol, a non-proprietary drug that is in the same class as sevelamer. The trial was an 8-week prospective feasibility study in stable hemodialysis patients, using colestipol as the only phosphate binder, preceded and followed by a washout phase of all other phosphate binders. The primary study endpoint was weekly measurements of serum phosphate. Secondary endpoints were serum calcium, lipids, and coagulation status. Analyses used random effects mixed models. 30 patients were screened for participation of which 26 met criteria for treatment. At a mean dose of 8.8g/24h of colestipol by study end, serum phosphate dropped from 2.24mmol/L to 1.

Two ml 0·5% bovine serum albumin (Sigma, St Louis, MO, USA) in IsoFlow (Beckman

Coulter, Lane Cove, NSW, Australia) was then added and the tubes centrifuged at 300 g for 5 min. After decanting supernatant, Fc receptors were blocked with 10 μl human immunoglobulin (Intragam, CSL, Parkville, Australia) click here for 10 min at room temperature. Five μl of appropriately diluted anti-CD8 FITC (BD), anti-CD3 PerCP-Cy5·5 (BD), CD28 PE-Cy7 (BD) and PE-conjugated granzyme B (BD), 10 μl undiluted perforin (BD) or isotype control monoclonal antibody was added for 15 min in the dark at room temperature. Cells were analysed within 1 h. Samples were analysed by live gating using FL3 staining versus side-scatter (SSC). A minimum of 10 000 CD3-positive, low-SSC Selleck SB203580 events were acquired in list-mode format for analysis. Control staining of cells with anti-mouse immunoglobulin (Ig)G1-PE/IgG-PC5 was performed on each sample and background readings of < 2% were obtained as described previously

[8]. Significant co-stimulatory molecule expression on T cells other than CD28 requires T cell stimulation similar to that required for intracellular cytokine production [14]. For CD154, CD152, CD137 and CD134, 1-ml aliquots of blood (diluted 1:2 with RPMI-1640 medium) were placed into 10 ml sterile conical polyvinyl chloride (PVC) tubes (Johns Professional Products, Sydney, Australia). Phorbol myristate (25 ng/ml) and ionomycin (1 mg/ml) were added to stimulate the T cells.

Brefeldin A (10 mg/ml) was added to prevent shedding of Phosphatidylinositol diacylglycerol-lyase the co-stimulatory molecules from the T cell surface, as reported previously [15]. The tubes were incubated in a humidified 5%CO2/95% air atmosphere at 37°C. At 16 h 100 ml 20 mM ethylenediamine tetraacetic acid/phosphate-buffered saline (EDTA/PBS) was added to the culture tubes, which were vortexed vigorously for 20 s to remove adherent cells. Three hundred microlitre aliquots of cells were treated with 2 ml FACSLyse for 10 min. Cells were centrifuged, supernatant discarded and 500 ml FACSPerm added for 10 min. Two ml 0·5% bovine serum albumin (BSA) (Sigma) in IsoFlow (Beckman Coulter) was then added and the tubes centrifuged at 300 g for 5 min. After decanting supernatant, Fc receptors were blocked with 10 ml human immunoglobulin (Intragam, CSL, Parkville, Victoria, Australia) for 10 min at room temperature. Five μl of appropriately diluted CD8 FITC [allophycocyanin (APC)-Cy7], CD3 PerCP-Cy5·5 (BD), CD28 PE-Cy7 (BD), CD45 V450 (BD) and PE-conjugated monoclonal antibodies to CD40L, CD152, CD137, CD134 or isotype control (BD) were added for 15 min in the dark at room temperature. Cells were washed and events acquired and analysed as described above.

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 selleck characterized by a necrotizing, granulomatous inflammation that predominantly involves upper airways, lungs and kidneys. The disease involves CCI-779 nmr 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 C1GALT1 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].