Actually, the degree of interstitial injury might become a better renal predictor than glomerular damages in chronic progressive glomerular diseases. Early interstitial change is included infiltration of inflammatory cells, but the finding can be reversible

by therapy. Thus, we evaluated the interstitial fibrosis as one of the indicators of renal prognosis in patients with LN. Methods: Forty-three patients who had been diagnosed as systemic lupus erythematosus Proteasome inhibitor (SLE) and performed renal biopsy in our department from 1987 to 2012 were enrolled. All patients were reviewed by means of ISN/RPS classification and were semiquantitatively evaluated interstitial fibrosis in the same way as described previously (no interstitial fibrosis:

0%, mild interstitial fibrosis: 0–25%, moderate interstitial fibrosis: 25–50%, severe interstitial fibrosis: >50%). Their blood and urinary examinations were evaluated at the time of renal biopsy and at the last follow up period. Results: According to ISN/RPS classification, renal function (SUN, sCre and eGFR) both at the time of biopsy and at the last Proteases inhibitor follow up period didn’t have statistical difference. When all patients were divided into semiquantitative interstitial fibrosis grade, there was no significant difference concerning about renal function at the time of biopsy. Renal symptoms of severe fibrosis grade presented significantly worse renal prognosis than other interstitial fibrosis grades

(no, mild and moderate interstitial fibrosis grade, respectively) at the last follow up period in the levels of SUN (p < 0.01), sCre (p < 0.05) and eGFR (p < 0.01, p < 0.05, p < 0.01, respectively). The serum SLE activity (C3, C4 and anti-DNA antibody) significantly ameliorated after appropriate treatments in spite of ISN/RPS classification or the interstitial fibrosis grade (data not shown). Conclusion: We should recognize the severe interstitial fibrosis as a eltoprazine predictor for worsening renal function and an independent factor from glomerular lesions or the serum SLE activity. ENDO NOBUHIDE, TSUBOI NAOTAKE, FURUHASHI KAZUHIRO, MATSUO SEIICHI, MARUYAMA SHOICHI Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan Introduction: In addition to the effector roles of classically activated macrophages for tissue injury, recent studies have shown that alternatively activated (M2) macrophages are involved in resolution of inflammation in animal models of kidney disease. But, clinical relevance of M2 macrophage in human disease is largely unknown.

Inclusion bodies were collected by centrifugation at 10,000 g for 10 min, and pellets FK866 were washed twice with TE buffer, twice with 0.5 m

NaCl, once with 0.5 m NaCl–1% Triton X-100, once with 0.5 m NaCl and once with cold distilled water and finally solubilized in CBP buffer (0.1 m Na2CO3 1% 2-mercaptoethanol [pH 9.6]). Particulate material was discarded by centrifugation at 10,000 g for 10 min, and the purified solubilized protoxin was stored at 4 °C and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein concentration was determined by the Bradford method [16], and purity was examined by SDS-PAGE. Endotoxin contamination in Cry1Ac protoxin preparations was tested using the E-toxate Part

1 kit (Sigma-Aldrich, St Louis, MO, USA ) with a limit of sensitivity of 0.05–0.1 endotoxin units (EU)/ml following manufacturer’s instructions. Endotoxin levels in the purified Cry1Ac protoxin preparations were below 0.1 EU/ml, but they were further treated with an excess of a polymixyn B resin (BioRad, Hercules, CA, USA) to remove any possible remnants of endotoxin BioRad. Immunization.  Nine groups of animals were i.n. immunized with Cry1Ac or administered with the vehicle to carry out three independent experiments for each assay type tested: (1) phenotypic and activation analysis, (2) cytokine assays and iii) Enzyme-linked immunospot (ELISPOT) assay. As a positive selleck screening library control for the ELISPOT assay was included a group of animals that were intranasally immunized with cholera Angiogenesis inhibitor toxin (CT; Sigma–Aldrich), which is considered the most potent mucosal immunogen. Each group (control and experimental) contained seven animals. For i.n. immunization, mice were lightly anesthetized with ethyl ether, and the antigen (in 30 μl of PBS) was delivered into the nostrils. For experimental group, 50-μg Cry1Ac doses were applied on days 1, 7, 14 and 21 by the i.n. route. For CT group, 10-μg doses were applied on same days. Control mice received 30 μl of PBS. Mice from each group were killed on day 28, and pooled lymphocyte suspensions from

the NALT and NP were obtained as described previously [8]. ELISPOT.  Specific anti-Cry1Ac or anti-CT Ab-secreting cells were enumerated by ELISPOT assay. Briefly, a 24-well plate with a nitrocellulose base (Millipore Corp., Bedford, MA, USA) was coated overnight at 4 °C with 10 μg of Cry1Ac or 10 μg of CT in PBS (500 μl per well). All wells were then blocked with 1% BSA in PBS for 120 min at room temperature. Lymphocytes (1 × 106 cells) were suspended in RPMI-1640 medium containing 5% FCS and added to each well (500 μl per well) and incubated for 4 h at 37 °C in 5% CO2 in air. The plates were thoroughly washed with PBS ± Tween and then incubated for 2 h at room temperature with 500-μl goat anti-mouse IgA α chain specific, peroxidase conjugated (Zymed Laboratories, Inc.

A variation in reactivity levels was found, with the same effector cells (effector A) showing higher

reactivity, as in the previous experiment. The results given are for the ADCC activity with NK values (reactivity without antibodies) subtracted. CD8+ Ganetespib cells were also tested as effector cells and, as expected, the activity without antibodies was overall at a negligible level, although with low, yet detectable ADCC activity for effector A cells and anti-HERV-H/F Gag antibodies. The results for both types of effector cells are shown in Fig. 5 both as increments where results with preimmune sera are subtracted from the results with immune sera and also as the value in folds (immune sera/preimmune sera). We find that increments are the most accurate and instructive values, as artificially increased values may result from calculating folds, when the denominator is below 1·0. The causative agent(s) initiating MS continues to evade exposure of their nature. The processes leading to cell death are also incompletely understood, although parts of the process are known, thus offering possibilities for different types of intervention in the course or the symptoms of the disease. Cytotoxicity reactions are not investigated greatly, either for the types of possible effector cells or for the antibodies/epitopes involved, although these reactions

may play a significant role in MS pathogenesis by killing CNS cells expressing the epitopes. The type of effector cells gaining most attention recently have been CD8+ T cells Palbociclib in vivo rather than CD4+ T cells [14, 15], which for several years were regarded as the main participants

in the disease processes [16], due in part to extensive investigations based on the animal model of brain inflammation, experimental autoimmune encephalomyelitis (EAE). This model has some similarities but also significant differences from MS, illustrated markedly by the lack of efficacy of clinical MS trials targeting CD4+ T cells [17]. Different types of cytotoxic activities of possible significance are due to NK [18] or ADCC, both executed mainly by CD56+ cells. In particular, the latter type of mafosfamide cytotoxicity may be worthwhile studying, as increased production of oligoclonal antibodies against both known and unknown epitopes (including HERV and herpesvirus epitopes) is one of the characteristic and puzzling findings in MS [19-21]. For several years we have grown blood lymphocytes from MS patients in our laboratory [9]. Some of these lymphocytes, particularly when sourced from MS patients in relapse, have changed the growth pattern into continuously growing B lymphoblastoid cell cultures expressing and producing endogenous retroviruses, predominantly HERV-H/F, and also HERV-W, together with low amounts of Epstein–Barr virus proteins.

NK cells are relatively easy to select from apheresis donations, but although typically approximately 5 × 108

cells can be obtained relatively pure, this may not represent a sufficient number for clinical efficacy [94]. Miller and colleagues therefore sought to expand transfused NK cells in vivo. Selected NK cells from HLA identical donors were transfused into 19 patients with high-risk AML after conditioning with low-dose total body irradiation or a combination of fludarabine and cyclophosphamide. The conditioning induced a rise of IL-15 and circulating NK cell numbers which showed enhanced cytotoxicity to leukaemia lasting more than 3 weeks. Five patients Everolimus achieved complete remission [95]. Other investigators have developed clinical-grade strategies to expand NK cells ex-vivo using B cell lines [96] or modified K562 cells [97]. Such techniques can yield 20–200-fold expansion of pure but activated NK cells over several weeks. Expanded cells are fully functional and kill leukaemia and tumour targets. Clinical trials using expanded NK cells have not yet been reported. Future developments may include combined

ex-vivo and in vivo expansion approaches. Allogeneic T cells selleck inhibitor can be raised against mHag by peptide-pulsed DC or AML cells and are being used in treatment of relapsed leukaemia after stem cell transplantation. Outside the context of SCT, the occurrence in patients of CTL specific for AML supports the possibility

of using expanded autologous antigen-specific CTL to attack AML [3,86]. Adoptive transfer of leukaemia-specific T cells presents different challenges according to whether the transfused T cells are autologous or allogeneic in origin. Treatment with allogeneic T cells requires immunosuppression of the recipient to permit at least the short-term survival of the transfused cells. Two studies of allogeneic T cell transfer in non-transplant recipients have been reported [98,99]. Haploidentical donor lymphocyte transfusions were given to patients with diverse malignancies, including 13 patients with high-risk AML. Transfusion was followed by a cytokine storm without any from sustained cellular engraftment, but there were tumour responses including five complete remissions in the AML patients [99]. Future developments will need to focus upon ways to achieve a short controlled engraftment sufficient to confer an anti-leukaemia effect perhaps by engineering T cells to escape immune attack, which may in turn require the co-insertion of a suicide gene as a safety precaution to prevent sustained persistence and expansion of the foreign T cell clone. Autologous T cell infusions can avoid the problems of alloreactivity of patient to donor or donor to patient. Here the problem is to generate sufficient numbers of T cells with powerful anti-leukaemia activity.

3–5 Once initiated the process of DCs maturation, the expression of CD80, CD86 and MHC class II molecules increases.1–4 The DCs migrate to the draining lymph nodes, as a result of the up-regulation of CCR7, which renders them responsive to CCL19 and CCL21 chemokines that direct their migration to the T-cell areas of lymph nodes.6 this website Finally, the mature DCs present the antigen to naive CD4+ and CD8+ T lymphocytes. The maturational

status can be modulated by different stimuli.5 The impact of microbial products through Toll-like receptor leads to DCs that produce interleukin-12 (IL-12)/IL-23 and prime T helper type 1 (Th1)/Th17 responses.7,8 In contrast, in the absence of inflammatory signals, ‘semi-mature’ DCs produce IL-10, which primes a regulatory T-cell response.9 However, mediators other than cytokines and pathogens have a great impact on the physiology of DCs. Prostaglandin E2 acting on mature DCs induces the differentiation of CD4+ T cells in a Th2 profile.10,11 Also, histamine activates murine DCs through the increase of endocytosis and cross-presentation of

extracellular antigens.12 Leukotriene C4 (LTC4), a member of the cysteinyl leukotriene family (CysLT), is a potent pro-inflammatory lipid mediator, produced by inflammatory cells such as mast cells, eosinophils, basophils and macrophages.13,14 It is a potent spasmogen and vasoconstrictor, promotes mucus secretion, and together with histamine is a known immunomodulatory agent of allergic and inflammatory reactions.15–17 The pharmacological effects of CysLT are conducted AZD2014 ic50 through two types of membrane receptors – CysLTR1 and CysLTR2 – which are coupled to protein-G.18 Remarkably, these receptors were primarily described at the level of lung mucosa and intestinal mucosa at the ileum and colon.19 In many diseases affecting lung and intestinal mucosa, such as asthma and interstitial cystitis, the use of montelukast, a selective antagonist of CysLTR1, minimizes the effects of these pathologies, probably through the

inhibition of cytosolic Ca2+.20–22 It is known that LTC4 induces the chemotaxis of DCs from the skin.23 Zymosan, a Toll-like receptor 2 agonist, but not lipopolysaccharide (LPS), a classic Toll-like Decitabine supplier receptor 4 agonist, stimulates the production of CysLT by DCs.24,25 Despite these observations, their impact on cytokine production by DCs is unclear. In spite of the close relationship between mast cells and DCs in mucosal epithelium and skin, little progress has been made regarding the impact of CysLT on the genesis of DCs. In the present study, we analysed the effects of LTC4 on the phenotype and function of murine inflammatory DCs.26 In particular, we studied the differential expression of CysLT1 and CysLT2 receptors in immature and LPS-activated DCs.

Precipitating CD177 from the neutrophil Selleckchem Bortezomib membrane and performing mass spectrometry, we found that several molecules co-precipitated with CD177. Among those proteins were the FcγIIIR as well as Mac-1 [55]. CD177 and Mac-1 co-localized, co-precipitated and showed direct protein interactions by plasmon-resonance analysis and when Mac-1 transfected cells interacted with immobilized NB1. We subsequently established that Mac-1 was a functionally important transmembrane component of the PR3 membrane complex, allowing subsequent PR3–ANCA-induced activation predominantly of mPR3high/NB1positive neutrophils (Fig. 2). However, we observed that degranulation and

extracellular superoxide generation, but not intracellular hydrogen peroxide formation depended on the mPR3 phenotype. Interestingly, PR3–ANCA were equally potent in inducing DHR oxidation selleck compound in mPR3high/NB1positive and mPR3low/NB1negative cells an observation also made by Hu et al. [27]. The underlying mechanism for this finding still needs to be elucidated. As mentioned, MPO membrane expression by neutrophils is somewhat scarce and much less is known as to how signalling is initiated after MPO–ANCA bind their target. Hess et al. found that large amounts of MPO can

be acquired by resting neutrophils from supernatants of activated neutrophils. This acquired surface MPO allowed MPO–ANCA binding and neutrophil activation [56]. Others showed that MPO is presented by CD11b promoting neutrophil activation even in the absence and presence of anti-MPO antibodies [57,58]. Initial studies on ANCA-induced signalling events showed that distinct intracellular signalling events Dichloromethane dehalogenase mediated ANCA-induced neutrophil

activation. Tyrosine kinase and protein kinase C activation by ANCA, but not by control IgG, was observed by Radford et al. [59]. Blocking both kinases using pharmacological inhibitors abrogated ANCA-induced superoxide generation. These experiments encouraged further characterization of the signal transduction cascade involved in ANCA-induced neutrophil activation. The implication was to block important key elements specifically and thereby identify novel and more specific treatment targets. P38 mitogen-activated protein kinase (MAPK) and extracellular regulated kinase (ERK) are important during both priming and the ANCA-induced neutrophil activation. Priming increases the amount of membrane-expressed antigens, but also sparks signalling pathways that are needed for a subsequent ANCA-induced full-blown activation. Both p38 MAPK and ERK are initiated during TNF-α priming and their blockade abrogates subsequent ANCA-induced activation. However, both pathways show differential effects in that p38 MAPK, but not ERK, controls the ANCA-antigen translocation [60].

1F). To analyze the interaction of LPL and calmodulin in more detail, we first analyzed the subcellular localization of calmodulin in T cells. In unstimulated cells that did not form a contact with APC, calmodulin and LPL were both equally distributed throughout the cytoplasm (Fig. 3A). Upon T-cell stimulation via superantigen-loaded APC for 45 min, in 48.09±0.16% of the T-cell/APC couples calmodulin translocated to the contact zone between T cells and APC where it colocalized with LPL. We reinforced this quantification by calculating the area corrected calmodulin

content within the contact zone of T cells and APC and subtracted an area corrected protein content within T-cell/T-cell and APC/APC contact zones 26. This analysis confirmed Carfilzomib mw that calmodulin and LPL accumulated in the T-cell/APC contact zone (Supporting

Information Fig. 2). The interaction of calmodulin and LPL was shown by calmodulin pull-down experiments (Fig. 3B). A binding of LPL to calmodulin could only be seen in the presence of EGTA. Note that the calcium/calmodulin dependent PD-1 inhibitor kinase type IV (CamKIV) was efficiently precipitated with calmodulin in the presence of calcium, whereas EGTA inhibited this interaction (Fig. 3C). These experiments explain at the same time the interaction of LPL and calmodulin in unstimulated cells, in which no calcium signal was induced (Fig. 3B). Although binding of LPL to calmodulin in the absence of calcium was Org 27569 unexpected, such interactions to calcium-free calmodulin (Apocalmodulin/ApoCam) were described for several proteins (reviewed in 27). We next analyzed whether inhibition

of calmodulin through the calmodulin antagonist W7 would lead to reduced LPL accumulation in the IS. MIFC analysis demonstrates that LPL recruitment was indeed diminished in the presence of W7 (Fig. 4A and B). The degree of inhibition is reminiscence of that observed for ΔCBD-LPL. Importantly, W7 also inhibited recruitment of the pSMAC-marker LFA-1, but not of the cSMAC-marker CD3 in the contact zone. The selective effects of W7 on the accumulation of pSMAC-markers in the IS was independently confirmed using LSM and EGFP-tagged LPL, F-actin or PKCΘ and staining of endogenous LFA-1 (Supporting Information Fig. 3). Also in these experiments the enrichment of LPL and the pSMAC-markers actin and LFA–1 were inhibited by W7, whereas it had no effect on the accumulation of the cSMAC-marker PKCθ in the IS. The reduced accumulation of ΔCBD-LPL (Fig. 1F), or of wt-LPL in the presence of calmodulin antagonists (Supporting Information Fig. 3) may be explained either by a diminished initial relocalization or a reduced maintenance of LPL in the contact zone. To discriminate between the two possibilities, we analyzed the relocalization kinetics and mean duration of wt-LPL and ΔCBD-LPL in the contact zone using time-lapse video-microscopy (TLV).

, 2005). Nonetheless, the major agonists (i.e. lipoproteins, lipopolysaccharide, flagellin, CpGs) that activate signaling by TLR2, 4, 5, and 9 are present in or on formalin-inactivated V. vulnificus HIF inhibitor cells. Moreover, the role of TLR4 in the host response to V. vulnificus, as suggested by ex vivo assays, was corroborated by infection studies with TLR4 KO mice. Thus, the use of inactivated cells for ex vivo assays to identify TLRs that could play a role in the host response to V. vulnificus infection is warranted despite potential caveats. The incidence of V. vulnificus infection is increasing due to climate change that favors survival and replication

of the organism and due to greater contact of humans with water and/or seafood harboring V. vulnificus (CDC, 2005; Vinh et al., 2006; Paz et

al., 2007; Dechet et al., 2008; Jones & Oliver, 2009). The high mortality rate resulting from V. vulnificus-induced septic shock and the long-term morbidity observed in survivors underscore the need for novel adjunctive treatments to improve patient outcome. This study has provided new information concerning the role of TLR4 in the host response to V. vulnificus. Such information is essential for developing therapeutic strategies that selectively www.selleckchem.com/products/AZD6244.html target the harmful TLR-mediated inflammatory response in order to prevent V. vulnificus-induced septic shock. I thank B. Vilen, S. Clarke, and J. Ting for TLR4 KO, MyD88 KO, and TNFα KO breeder mice, respectively, and P. Stewart for advice on statistical analyses. This study was supported by the UNC-CH Department of Epidemiology Infectious Diseases Trust Fund. The UNC-CH Immunotechnologies Core is supported by NIH grant P30 DK34987. “
“Human cartilage

gp-39 (HC gp-39) is a well-known autoantigen in rheumatoid arthritis (RA). However, the exact localization, fluctuation and function of HC gp-39 in RA are unknown. Therefore, using a glucose-6-phosphate isomerase (GPI)-induced model of arthritis, we investigated these aspects of HC gp-39 Ergoloid in arthritis. The rise in serum HC gp-39 levels was detected on the early phase of GPI-induced arthritis (day 7) and the HC gp-39 mRNA was increased significantly on splenic CD4+T cells on day7, but not on CD11b+cells. Moreover, to identify the characterization of HC gp-39+CD4+T cells, we assessed the analysis of T helper (Th) subsets. As a result, HC gp-39 was expressed dominantly in CD4+CD25+ forkhead box protein 3 (FoxP3)+ refulatory T cells (Treg), but not in Th1, Th2 or Th17 cells. Furthermore, to investigate the effect of HC gp-39 to CD4+T cells, T cell proliferation assay and cytokine production from CD4+T cells using recombinant HC gp-39 was assessed. We found that GPI-specific T cell proliferation and interferon (IFN)-γ or interleukin (IL)-17 production were clearly suppressed by addition of recombinant HC gp-39.

However, influx of Th1 and innate immune cells was not compromised in the absence of IL-23. IL-22 and IL-23 play either redundant or minimal roles in the pathogenesis of Chlamydia infection in the mouse model. Induction of Th17-associated cytokines by a Chlamydia vaccine should be avoided as these responses are not central to resolution of infection and have pathologic potential. “
“There is limited

insight into the mechanisms involved in the counterregulation of TLR. Given the important role of TLR3/TIR domain-containing Trichostatin A mw adaptor-inducing IFN-β (TRIF)-dependent signalling in innate immunity, novel insights into its modulation is of significance in the context of many physiological and pathological processes. Herein, we sought to perform analysis to definitively assign a mechanistic role for MyD88 adaptor-like (Mal), an activator of TLR2/4 signalling, in the negative regulation of TLR3/TRIF signalling. Biochemical and functional analysis demonstrates that Mal negatively regulates TLR3, but not TLR4, mediated IFN-β

production. Co-immunoprecipitation experiments demonstrate that Mal associates with IRF7 (IRF, IFN regulatory factor), not IRF3, and Mal specifically blocks IRF7 activation. In doing so, Mal impedes TLR3 ligand-induced IFN-β induction. Interestingly, Mal does not affect the induction of IL-6 and TNF-α upon TLR3 ligand engagement. Together, these data show that the TLR adaptor Mal interacts with IRF7 and, in doing so, impairs Sitaxentan IFN-β induction through Trametinib the positive regulatory domains I-III enhancer element of the IFN-β gene following poly(I:C) stimulation. Our findings offer a new mechanistic insight into TLR3/TRIF signalling through a hitherto unknown mechanism whereby Mal inhibits poly(I:C)-induced IRF7 activation and concomitant IFN-β production. Thus, Mal is essential in restricting TLR3 signalling thereby protecting the host from unwanted immunopathologies associated with excessive IFN-β production. TLR are important

participants in the first line of defense against invading pathogens 1, 2. Upon ligand activation of the TLR, cytosolic Toll/IL-1 receptor (TIR) domain-containing adaptor proteins are recruited 1, of which, four activating adaptors have been identified, Myeloid differentiation factor 88 (MyD88), MyD88 adaptor-like (Mal)/Toll-IL-1 adaptor protein (TIRAP), TIR domain-containing adaptor-inducing IFN-β (TRIF) and TRIF-related adaptor molecule (TRAM). Despite the TLR having somewhat similar signal transduction pathways, there is specificity with regard to their adaptor usage 3. MyD88 is the common downstream adaptor that is recruited by all TLR except TLR3 4. Mal is required for signalling by TLR4 and TLR2 5, though it has recently been reported that Mal is not essential for TLR2 signalling 6.

If possible, these must be replaced with an alternative agent such as angiotensin receptor blocker. While there are some anecdotal reports [82] in the literature of severe anaphylaxis to VIT in patients on concurrent treatment Fostamatinib with ACE inhibitors, a recent retrospective study in a small cohort of patients did not confirm this observation [83]. There is some evidence in the literature from studies in a small group of subjects that premedication with antihistamine reduces severity

of histamine-mediated local reactions, including erythema and induration, and generalized cutaneous response such as urticaria and angioedema, but they do not prevent or abrogate anaphylaxis [65,84,85]. Some allergists express concern about antihistamines potentially masking early symptoms of an allergic reaction to injections, but this is not evidence-based. It is worth noting that recent large multi-centre SCIT hay fever trials included premedication with a short-acting antihistamine [11]. The purpose of allergen standardization is to enhance sensitivity and specificity of the extracts used for diagnosis of allergy as well as to

minimize the qualitative and quantitative variation in the composition of the vaccines in order to obtain higher safety standards, efficacy and accuracy. The first international initiative on allergen standardization was the establishment of the Nordic Guidelines, based on Danish Allergen Standardization in 1976 [86]. The World Health Organization (WHO) and European Pharmacopoeia have published guidelines on allergen standardization. Buparlisib concentration In Europe, current guidelines dictate the use of ‘in-house’ reference preparation (IHRP) by all manufacturers for monitoring ‘batch-to-batch’ control [87,88]. The source material for allergy vaccines should represent the allergen to which Baricitinib humans are exposed and should meet the specified criteria for limits on foreign substances and be free of microbial contamination [86]. The manufacturing process must not alter the immunogenicity of the vaccine. A major aspect of allergen standardization

is to control for total allergenic potency, which is achieved with international collaboration between manufacturers and control authorities using the same standards that are available from the National Institute of Biological Standards and Control, Herts, UK [86]. The ‘in-house’ reference preparation used by individual laboratories is compared with the international standard and ‘batch-to-batch’ control involves monitoring the quantity of major allergens [86]. Another approach has been to use chemically modified allergens (allergoids) treated with formaldehyde or glutaraldehyde, which reduce allergenicity (IgE binding) but retain immunogenicity, and so theoretically would reduce the incidence of systemic reactions [86]. These are available for a number of allergens on a named patient basis, including pollens, house dust mite, animal dander and fungal spores.