Deficiencies of the enzymes catalysing the former two products

are responsible for the primary GSK126 order hyperoxalurias. Erythrocyte metabolism and ascorbic acid catabolism can also contribute to the oxalate load. Only free oxalate can be absorbed by the intestinal epithelium. The amount of free oxalate is dependent on the concentration of other ions in the intestine, mainly calcium, and the bioavailability in the food consumed. Normally calcium will bind oxalate preventing its absorption. In patients with cystic fibrosis, lipid malabsorption, associated with pancreatic insufficiency and prior intestinal surgery, would result in undigested lipids preferentially binding calcium, leaving unbound oxalate free to be absorbed in large quantities. Lipid malabsorption increases the exposure of the colonic mucosa to bile and free fatty acids, increasing mucosal permeability for oxalate. Oxalobacter formigenes, a gut anaerobe capable of metabolizing oxalate, can be eradicated by multiple antibiotics,

further increasing oxalate absorption. Cystic fibrosis is now one of the commonest reasons for lung transplantation and postoperative renal failure is common. In a case series published by Lefaucheur et al.,1 in 2008, 77 patients with cystic fibrosis were followed up post https://www.selleckchem.com/products/BAY-73-4506.html lung transplant. Twenty-five patients developed accelerated renal function loss, 15 of whom underwent a renal biopsy. Oxalate crystals were present in the tubular epithelium of nine of these patients. Three of these patients progressed to end-stage renal disease. Oxalate is freely filtered by the glomerulus and secreted by the proximal tubules and is minimally protein bound. The diagnosis of hyperoxaluria can be made by demonstrating an elevated 24 h urine oxalate excretion (normal <550 µmol/day). However, levels >2000 µmol/L are often noted in the primary hyperoxalurias together with elevated levels of glycolate and glyoxylate. In our patient, tubular epithelium damage, because of various drug and haemodynamic Megestrol Acetate insults, would have provided the perfect nidus for oxalate deposition.

Oxalate crystals can aggregate and obstruct the tubular lumen or be internalized into the tubular cells where they can lead to further tubular injury. The rationale for the use of calcium carbonate and addition of Sevelamer to the diet was to bind intestinal oxalate directly and to also bind intestinal phosphate thus freeing up intestinal calcium to then bind oxalate. Systemic oxalate deposition can result in retinopathy, arthropathy, conduction defects and peripheral neuropathy. Cases have also been reported of patients with an occult diagnosis of primary hyperoxaluria who received a renal transplant with prompt graft failure because of severe renal oxalate deposition. Therefore in addition to enzyme replacement and dietary supplementation, intensive dialysis was initiated to prevent systemic complications of oxalosis.

Atherosclerotic renovascular disease (ARVD), long recognized as an important cause of secondary hypertension, is increasingly identified

as a cause of chronic kidney disease (CKD) in our aging population. Despite an extensive literature, decisions regarding its investigation and treatment are challenging, with a paucity of firm evidence for even the most established indications to intervene. Frequently, ARVD is a silent condition intertwined with other atheromatous disease as part of a systemic vascular equivalent of the metabolic syndrome. A complex dynamic exists between intrinsic renal damage from microvascular disease and microemboli, hypertension, and resulting cardiac abnormalities. Atherosclerotic renal artery stenosis (RAS) describes the physical narrowing within the renal artery and is often an incidental finding. As will be discussed, the optimal treatment for YAP-TEAD Inhibitor 1 most such lesions is uncertain.1,2 As some patients present with renal artery occlusion it is more

accurate to use the term ARVD to describe overall patient populations with renal atheroma. Prior to the publication of Angioplasty and Stenting for Renal Artery Lesions (ASTRAL),3 the largest trial in ARVD to date, there had only been five small randomized control trials (RCT)4–8 assessing the value of revascularization therapy in ARVD. Despite the findings of ASTRAL and the other RCT, some questions are still unanswered with conclusions and debate drawn from subgroup analyses. Given many

cases are incidental findings or remain asymptomatic, PD-0332991 cost the true prevalence of ARVD is almost certainly underestimated. In the UK, ARVD is defined as the primary disease in 10.8% of incident dialysis patients aged over 65 years.2 In the general population, Mirabegron a community based study using Doppler ultrasound found nearly 7% prevalence of significant AVRD in elderly subjects.9 Recent data in which patients presenting to the emergency room who were found to be hypertensive were screened for RAS found significant disease in over 8%.10 Claims data from a random sample of Medicare patients aged >65 years in the USA found the incidence of ARVD to be 3.7 per 1000 patient-years or 0.5% in the general adult population.11 Unsurprisingly given the systemic nature of vascular disease, patients already being investigated for disparate arterial disease have a higher incidence of incidental disease. Significant RAS is found in almost 40% of patients investigated for lower limb vascular disease or aortic disease and between 15% and 29% of patients undergoing diagnostic coronary angiography.12,13 The RAS is often bilateral. In 2439 patients undergoing coronary angiography, 19% were found to have evidence of RAS, in which 26% (5% overall) had bilateral disease.

The HT-29/tslp-23 and the Caco-2/tslp-6 were selected for their response to 10 ng/mL

of IL-1β after 24 h stimulation. In transient transfections assays, 1.0 × 106 cells (HT-29 and Caco-2) were transfected with 1 μg of the selected plasmid using the AmaxaR Nucleofector kits (Lonza). After transfection, cells were seeded at 9 × 104 cells/well and cultured for 18 h before stimulation with IL-1β (10 ng/mL). The empty pcDNA-Luc plasmid was used as control. Co-transfection with a plasmid harboring the SEAP driven by CMV promoter (pCMV-SEAP) was used for normalization. Luciferase activity, quantified as relative luminescence units, was measured using the ONE-GloTM Luciferase Assay System learn more (Promega) according to the manufacturer’s instructions using a microplate reader (Infinite 200, Tecan). Caco-2 cells were grown for 1 week in 24-well plates (100 000 cells/well) and media was changed every day. Supernatants from 8-, 24-, and 48-h-stimulated Caco-2 cells were collected, centrifuged at 1200 rpm for 5 min at 4°C and analyzed using the “Human TSLP ELISA Development Kit” (PeproTech) following the manufacturer’s instructions. Nuclear extracts were prepared as described in [41].

In brief, five microgram of nuclear extracts were incubated at room temperature for 20 min with 0.07 pmol (50–200 000 cpm) of double stranded (32P)-labeled oligonucleotide probes containing consensus binding sequences for NF1 and NF2 sites, then separated by electrophoresis and visualized by autoradiography. EMSA supershifts Compound Library cell assay were performed using 1 μg of specific NF-κB antibodies against the p50 and p65 subunits Adenosine triphosphate (Santa Cruz Biotechnology). For competition assay, the reaction was pre-incubated with 1000-fold molar excess of unlabeled probe for 30 min at room temperature before the addition of labeled probe. The oligonucleotides used as probes were as follows: NF1 fw 5′-CTGCTAGGGAAACTCCATTATTAC-3′; NF2 fw 5′-AGGTGAGGGAAATTCCTGATGACT-3′;

NF1M fw 5′-CTGCTAaattAACTCCATTATTAC-3′; NF2M fw 5′-AGGTGAaattAATTCCTGATGACT-3′. Presented results were representative of at least three independent experiments. Results were expressed as mean ± SD of triplicate measurements of a representative experiment. Data were analyzed by Student’s t-test. This work was supported by grants from the European Community’s Seventh Framework Programme (FP7/2007–2013): MetaHIT, grant agreement HEALTH-F4-2007-201052. TdW, DK, JD, and HB are partners of the European Marie-Curie Initial Training Network Cross-Talk (grant agreement # 215553). TdW has been supported by the French National Research Agency (ANR) funded project, MicroObes. We thank Pierre Chambon for sharing unpublished results, Ronan Legoffic for helpful discussion and Karine Le Roux for technical assistance. The authors declare no commercial or industrial conflict of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors.

To our knowledge, this is the first case report of post-transplantation check details EPS that has been treated with everolimus. One previous case report suggested favourable use of everolimus for a non transplant, peritoneal dialysis patient who developed EPS.[4] Everolimus, in addition to its immunosuppressive effects through mammalian target of rapamycin (mTOR) inhibition, has well known antiproliferative

properties for which it has been used therapeutically. In rat models, it has been shown to have beneficial effects on reducing peritoneal fibrosis.[5] In this case a combination of treatment modalities, including everolimus, tamoxifen, corticosteroids, stopping CNI, intermittent total parenteral nutrition and surgery, were utilised to result in a successful outcome

for the patient. Surgery was essential in gaining immediate control over life threatening symptoms. However, it is not possible to determine MK0683 cost which of these treatments has had the greatest benefit, as no uniformly successful therapy for EPS exists at present. Tamoxifen is the most studied medical treatment, but to our knowledge, its use has only been reported in small case series of non-transplant patients, and only in case studies of EPS post renal transplantation.[6] Surgical treatments for EPS are reported in larger case series, but recurrence rates are high.[6] The immunosuppressive and antiproliferative properties of everolimus give it a theoretical role for use in the disease. With no effective management for EPS, prospective randomised controlled trials of this rare disease are required. To further investigate the role for everolimus in EPS, one approach would be to randomise patients at high risk of EPS post renal transplantation to standard CNI based immunosuppression versus switch to an everolimus based maintenance immunosuppression. “
“Introduction:  Peritoneal dialysis MycoClean Mycoplasma Removal Kit (PD)-related infections due to rapidly growing nontuberculous mycobacterium (RGNTM) are rare in Asians and have variable clinical outcomes. Methods:  We analysed retrospectively a series of RGNTM

infections in a single-centre multi-ethnic Asian population over a 5-year period. Clinical features, treatment, risk factors and outcomes are discussed. Results:  Ten infections are described. They constituted 3% of all culture-positive exit site infection (ESI) and PD peritonitis. Seventy percent were due to Mycobacterium abscessus (three ESI and four peritonitis). There were two Mycobacterim fortuitum and one Mycobacterium chelonei peritonitis. No specific findings differentiated RGNTM infections from those caused by traditional organisms. Six cases had received prior antibiotics, two being topical gentamicin. Initial routine culture and alcohol acid fast bacillus were negative except for one case of M. abscessus. A confirmatory diagnosis was made a median 9 days post culture. No infection responded to routine antibiotics.

The cska-TCRs, in conjunction with surrounding adhesion molecules as LFA1 and CD2 [34, 35], and additional bundling proteins, maintain the specific polar orientation of cytoskeleton structures and a sustained T-cell–APC interaction. These are necessary for optimal cytokine synthesis and polar secretion toward the T-cell–APC interface, events critical for the activation of the T cells and the corresponding www.selleckchem.com/products/abt-199.html APCs, as indicated by expression of CD25 and CD69 on both cell types. The presented model demonstrates the pivotal role of the cska-TCRs in resting T cells and in both early and late processes of T-cell activation. Moreover, our novel results fill the

missing gap that was puzzled by numerous studies, aiming at understanding the mechanism underlying IS formation and maintenance, by showing that the TCR is directly connected to the cytoskeleton and that the cska ζ “guide” the initial activation signal via the TCR toward a subsequent actin-dependent receptor cluster formation. Female BALB/c mice were bred in the Hebrew University SPF facility. ζ KO and transgenic ζ DISTAL and TAIL-LESS mice were kind gift of Dr. buy Ganetespib W.E. Shores from the NIH [13]. Splenocytes were isolated

from 6- to 12-week-old mice. 2B4 T-cell hybridoma and its ζ-deficient variant (MA5.8) expressing full length (FL) and truncated (CT-150 and CT-108) ζ were used. The Abs used are: A2B4 clonotypic Abs, anti-CD3ε, and anti-ζ, as previously described [8], anti-ZAP70 was a gift from L.E. Samelson (NIH), anti-CD3δ, anti-GST-LAT, Niclosamide and anti-GST were generated in rabbits, anti-Thy1.2 Abs (Serotek), anti-CD3ε, anti-CD28, anti-CD25, anti-CD69, and anti-IL-2 (BD Pharmingen), anti-CD16/32 and H57 (Biolegend),

anti-phosphotyrosine (4G10) (UBI), anti-actin, and anti-pLAT (Abcam), Streptavidin-Cy5 or-allophycocyanin (Jackson Immunoresearch). Polyclonal Abs, “b”, “c”, and “d”, directed against different epitopes within ζ, were generated in rabbits, and H-l46 anti-ζ (Ab “a”) Abs were generously provided by Ralph Kubo, USA. dscf and dicf were separated from tested cells and when indicated, proteins were immunoprecipitated. Samples were separated on 1D or 2D nonreducing/reducing SDS-PAGE and subjected to Western blot analysis. The above-mentioned procedures and those for biotinylation and activation of splenocytes were previously described [10]. Ezrin and IκB were used in all experiments as control proteins to verify efficacy of detergent-insoluble and -soluble fractionation, respectively, and the ratio between dscf and dicf proteins were determined by densitometry analysis. Site-directed mutagenesis of murine ζ was performed using Pfu DNA polymerase (Stratagene) according to the manufacture’s protocol. Double mutated (MUT) cDNA was sequenced and cloned into pcDNA3 (Invitrogen) for transfection or into pGEX6p2 to generate GST recombinant proteins.

Monocytes isolated from PBMC of healthy donors (n=15) displayed similar expression

levels of CD300e (Fig. 1A) that were not modulated upon overnight activation with LPS (data not shown). The CD300e expression by peripheral HIF inhibitor blood mDC is shown in Fig. 1B. To characterize CD300e-mediated activation, we first investigated its ability to induce intracellular Ca2+ mobilization. Engagement of CD300e with a soluble anti-CD300e mAb (UP-H2) did not modify the [Ca2+]i in indo-1 AM-loaded monocytes within 5 min (data not shown). Yet, upon cross-linking with an F(ab′)2 anti-IgG Ab, a rapid and transient increase of intracellular [Ca2+]i was detected, when compared with the lack of response in cells stimulated under the same conditions with an isotype-matched control mAb (MOPC-21) (Fig. 2A). To further explore the functional consequences of CD300e-mediated signaling, we tested the production of ROS. Superoxide anion O production was detectable 30 min after CD300e ligation and increased along the following 2.5 (Fig. 2B). As shown in Fig. 2C, stimulation of monocytes for 3 h with plate-coated anti-CD300e mAb (UP-H2) promoted a significant increase of O (7.95±0.91 nmol/106 cells), when compared with cells treated with the isotype-matched control mAb

(1.92±0.68 nmol/106 cells) or incubated alone (1.57±0.57 nmol/106 cells); a specific Hydroxychloroquine mAb for triggering receptor expressed on myeloid cell 1 (TREM-1) was used as a positive control (19.51±0.01 nmol/106 cells). To further investigate the functional role of CD300e, monocytes were stimulated for 24 h with plate-coated mAb and analyzed for the Immune system expression of surface molecules known to be upregulated upon activation. Basal expression of these molecules in freshly isolated monocytes is shown in Fig. 3A. When compared with cells treated with an isotype-matched control mAb, the levels of CD25, CD83 and CD86 increased in samples stimulated with anti-CD300e mAb, whereas

CD40 and CD54 expression remained unaltered (Fig. 3B). Moreover, cross-linking of CD300e induced a significant production of pro-inflammatory chemokines and cytokines (i.e. IL-8/CXCL8 and TNF-α) (Fig. 3C) that was not further enhanced by LPS-mediated priming (data not shown). Similar studies were performed in freshly isolated mDC, stimulated for 24 h with LPS or plate-coated mAb (Fig. 4B). Compared with freshly isolated cells (Fig. 4A) and control treatments (Fig. 4B), both LPS and anti-CD300e induced mDC activation as revealed by the upregulation of CD40, CD83 and CD86 co-stimulatory molecules. Moreover, CD300e ligation also triggered TNF-α, IL-6, IL-8/CXCL8 and IL-10 production by mDC (Fig. 4C), whereas no IL-12p70 was detected (data not shown). Under these experimental conditions, the production of TNF-α by mDC in response to LPS stimulation was low, in line with a previous report 21.

The emergence of the epidemics in the East United States, the rapid evolution of host resistance and the persistence of immunologically naïve populations in the West can almost be considered as a natural experiment that might allow to test the following predictions: if the cost of infection is mostly due to the direct damage of the pathogen, then hosts from Arizona

(the nonexposed population) should suffer Selleck Idasanutlin the most; if immunological resistance incurs costs and these constitutes the bulk of the fitness reduction in infected birds, then exposed (Alabama) hosts should suffer the most. Bonneaud et al. [73] used the same populations of house finches to measure changes in body mass intervening during the first 14 days post-infection as a proxy of infection cost. Overall, birds from the coevolved population lost more body mass than birds from the naïve population, and interestingly, the relationship between bacterial load and loss in body mass was reversed in the two populations (Figure 5a). Whereas bacterial load was negatively correlated with body mass loss in Arizona birds, indicating that most heavily infected birds lost more mass, the sign of the correlation was reversed in Alabama birds. Birds with the lowest bacterial load suffered the most intense mass reduction in Alabama. One possible interpretation of these results LY2109761 in vivo is that body mass loss represents two different components of the cost of the infection

in the two populations: cost of immunological resistance in Alabama and cost of parasite damage in Arizona. In Branched chain aminotransferase agreement with this view, the pattern of immune gene expression (indicating a protective immunity) was associated with a higher body mass loss in Alabama than in Arizona (Figure 5b). These results therefore nicely confirm in a more natural setting the findings reported for malaria parasites. Immunological

costs, whatever their nature (energetic or self-reactivity) and whatever the conferred protection (resistance or tolerance), substantially contribute to determine parasite virulence. More recently, Adelman et al. [74] explored explicitly the role played by inflammatory effectors in the resistance/tolerance of house finches experimentally infected with Mycoplasma gallisepticum. They used the same house finch populations (Alabama and Arizona) studied by Bonneaud et al. [71-73], but birds were infected with a strain of Mycoplasma isolated soon after the emergence of the epidemics. They also focused on pro- (IL-1β) and anti-inflammatory (IL-10) effectors as mediators of tolerance to infection. Interestingly, they showed that birds originating from Alabama were more tolerant to the infection (they had a better health for a given pathogen load), even though this depended on the method used to assess tolerance, than birds from Arizona. Birds from Alabama also had a lower expression of the pro-inflammatory cytokine IL-1β.

, 1994). Other species are more frequently associated with enteric disease, particularly travelers’ diarrhea (Yoh et al., 2005), although sporadic cases of meningitis (Sipahi et al., 2010) and ocular infections (Koreishi et al., 2006) also have been reported. The serological scheme of P. stuartii, P. rustigianii, and P. alcalifaciens used RGFP966 molecular weight in

serotyping of clinical isolates is based on O-antigens present on the cell surface and flagella H-antigens; it includes 63 O-serogroups and 30 H-serogroups (Ewing, 1986). Recently, it has been found that strains representing serotypes O58:H9 and O59:H18 must be reclassified from the genus Providencia to Morganella morganii (A. Rozalski, unpublished data). The O-antigen represents the O-polysaccharide chain of the lipopolysaccharide (LPS) built up of oligosaccharide repeats (O-units). Some Providencia O-antigens show a similarity to those of a closely related genus Proteus (Torzewska et al., 2004a, b) as well as taxonomically remote bacteria, such as Pseudoalteromonas flavipulchra (Kocharova et al., 2006) and Shewanella fidelis (Kocharova et al., 2011) from the family Alteromonadaceae. To create a molecular basis for the serological classification of

Providencia and to substantiate their antigenic relationships to other bacteria, the O-antigen structures have been elucidated in the majority of Providencia O-serogroups

(Knirel, 2011). Biosynthesis of the O-antigen by the FK506 solubility dmso next most common O-antigen polymerase (Wzy)-dependent pathway (Valvano, 2011) requires three major groups of enzymes: (i) sugar biosynthetic pathway enzymes that synthesize the nucleotide-activated form of each unique sugar present in the O-unit; (ii) glycosyltransferases that sequentially transfer the precursor sugars to assemble an O-unit on the undecaprenyl diphosphate lipid carrier anchored into the inner membrane facing the cytoplasmic side; and (iii) O-antigen processing proteins that are involved in translocation of the O-unit across the inner membrane to the periplasmic side (flippase Wzx) and polymerization (O-antigen polymerase Wzy and modal chain length regulator Wzz). Most of the genes encoding these enzymes are not scattered around the chromosome but are combined into a gene cluster that maps between two conserved genes. Recently, putative O-antigen gene clusters have been found between the cpxA and yibK genes and characterized in nine Providencia strains (Ovchinnikova et al., 2012). In this paper, we report on the O-antigen structure of P. alcalifaciens O40 and its serological relationships to the O-antigens of some other Providencia serogroups. In addition, the O40-antigen gene cluster was sequenced and analyzed and found to be in agreement with the O-polysaccharide structure established.

8% vs 9.8%).42 In another cross-sectional study of 80 CKD patients, FGF-23 levels were significantly associated with deteriorating renal function and decreased calcitriol levels.43 FGF-23 levels were elevated at an earlier stage of CKD compared with serum phosphate, which was more likely to be elevated in advanced CKD. An analysis of 792 patients with stable CVD demonstrated a continuous rise in FGF-23 levels at an eGFR < 90 mL/min.37 The recent Study for the Evaluation of Early Kidney Disease (SEEK), which involved 1814 Canadian participants,

demonstrated calcitriol deficiency in 12% of patients with an eGFR > 80 mL/min, higher than at previously reported eGFR. Available data supports a correlation between FGF-23, decreased eGFR and the biochemical changes of SHPT. However, prospective, longitudinal data and time-specific correlation between FGF-23 levels and biochemical Ibrutinib supplier parameters of SHPT are needed. The significance of the extremely elevated FGF-23 levels seen in CKD patients on dialysis remains poorly understood. It has been postulated that this process may be mediated by a change in Klotho expression resulting in relative resistance to FGF-23, along with as yet unrecognized factors. There is also a lack of conclusive data about the short- and long-term effects of phosphate intake on elevated FGF-23 levels in CKD. Recent research into the metabolic and bone complications

Dolutegravir of CKD has focused on local, bone-derived factors that may modulate

these changes. The relationship between bone turnover and serum FGF-23 was studied in several mouse models, where bone turnover was altered Tyrosine Kinase Inhibitor Library high throughput by a variety of exogenous and endogenous factors.44 The administration of osteoprotegerin (OPG), a potent anti-resportive agent, resulted in a rise in serum FGF-23, which occurred after reduction in bone turnover and was proportionate to the degree of suppression. The converse was observed after administration of exogenous PTH, with increased osteoblastic activity and reduced serum FGF-23. These findings suggest that bone remodelling and the rate of bone formation may modulate FGF-23 synthesis and release. In a recent study of 32 patients with CKD stages 2–5, plasma FGF-23 levels were inversely related to eGFR; however, the amount of bone FGF-23 expression was not related to the degree of renal impairment.45 These findings reflect the complexity of FGF-23 metabolism in normal and CKD patients and highlight the deficiencies in our understanding of FGF-23 and its relationship to CKD-MBD. The various biochemical markers of CKD-MBD have all been variably associated with clinical outcomes in CKD. Elevated serum phosphate and to a lesser extent deficiency of 25-hydroxyvitamin D and calcitriol have been associated with adverse outcomes,2–4,46–51 although much of this evidence is from observational studies.

53%) healthy controls. TSGA10 autoantibodies were not detected in the serum from patients with any other autoimmune disease. Autoantibodies against TSGA10 were detectable from a young age in 4/5 positive Rapamycin datasheet APS1 patients with autoantibody titres remaining relatively constant over time. Furthermore, real-time PCR confirmed TSGA10 mRNA to be most abundantly expressed in the testis and also showed moderate and low expression

levels throughout the entire body. TSGA10 should be considered as an autoantigen in a subset of APS1 patients and also in a minority of SLE patients. No recognizable clinical phenotype could be found to correlate with positive autoantibody reactivity. Autoimmune polyendocrine syndrome type 1 (APS1; alternatively known as autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy, APECED) is a rare monogenic autoimmune disease resulting from mutations in the AIRE gene. The AIRE gene plays a vital role in the removal and inhibition of self-reactive T cells in the thymus [1–3], a breakdown of which consequently leads to the development of the organ-specific autoimmune disease APS1. The disorder is characterized by the classical triad of chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, the presence of at least two of these are traditionally required for the diagnoses. These

components begin to manifest in the first decade of life, often followed by the progressive emergence of other organ-specific autoimmune diseases including gonadal failure, MK-2206 nmr intestinal dysfunction and insulin-dependent diabetes mellitus as well as ectodermal manifestations, all with variable penetrance. Pituitary manifestations are another lesser described component of APS1, being diagnosed in approximately 7% of all APS1 patients [4]. Patients present with single or multiple pituitary deficits, the most commonly reported deficit being isolated

growth hormone (GH) deficiency [5]. Partial adrenocorticotropin hormone deficiency, isolated hypogonadotrophic hypogonadism, central/idiopathic diabetes insipidus [5–11] and lymphocytic hypophysitis [12] have also been described. Pituitary autoantibodies in APS1 sera have been detected against both lactotrophs and CYTH4 gonadotrophs using immunohistochemistry [5, 13, 14]. APS1 patients also have autoantibodies directed towards a small number of guinea pig anterior pituitary cells, 40–50% of which are GH-producing cells [15]. In addition, a fibre-plexus staining pattern is observed in the pituitary intermediate lobe. Several of the major APS1 autoantigens previously identified are involved in monoamine and gamma-aminobutyric acid (GABA) synthesis and are expressed in pituitary tissue. APS1 patient sera target aromatic l-amino acid decarboxylase (AADC) and tyrosine hydroxylase (TH) in the anterior pituitary and glutamic acid decarboxylase 65 (GAD) in the intermediate lobe [13, 15], yet these do not account for the entire immunostaining seen.