In addition, we examined the ability of human CD4 and CD8 T cells from NSG mice implanted with human thymic and liver tissues and injected with autologous HSC to produce cytokines following an in-vitro polyclonal stimulation with PMA and ionomycin (Supporting information, Fig. S5). CD4 T cells from mice that received no irradiation or 200 cGy were able to produce IFN-γ, IL-2, IL-17A and IL-22, with slightly higher levels of IL-2-producing CD4 T cells detected in mice that were not irradiated. IFN-γ and IL-2-producing CD8 T cells were detectable from both groups of mice. Higher levels of CD8 T cell-producing

IFN-γ were detectable in the 200 cGy group, and higher levels of IL-2-producing CD8 T cells were detected Napabucasin mw in the 0 cGy group. Together, these data indicate that the implantation of human thymic tissue into NSG mice supports high levels of T cell development in the absence of irradiation following injection of autologous HSC. Human B cells develop in the standard BLT model, and these cells are functional, producing

antigen-specific Ig following viral infections [24, 38]. We therefore evaluated the importance of irradiation for B cell development and function in either NSG mice injected with human HSC only or NSG mice implanted with human thymic and liver tissues and injected with autologous HSC. CD20+ B cells accounted for a large proportion of the human CD45+ cells in the GSK1120212 in vivo blood at 12 weeks (Fig. 3a) and in the blood (Fig. 3b) and spleen (Fig. 3c) at 16 weeks in NSG mice that were injected with HSC

only. In HSC-engrafted NSG Sitaxentan mice that were implanted with human thymic tissues, the percentages of human B cells in the blood and spleen were not significantly different between mice that were non-irradiated versus irradiated. However, there was a significant decrease in the total number of human B cells in spleen of mice that did not receive irradiation (Fig. 3d). To assess the overall functionality of the human B cells, the levels of human IgM and IgG present in the serum of engrafted mice were determined at 12 weeks. NSG mice that received irradiation had significantly higher levels of human IgM compared to mice that were not irradiated (Fig. 3e). Human IgG levels were detected at very low levels in all groups of mice (Fig. 3f), and this is consistent with other studies using BLT mice [37, 38]. To determine if irradiation influences the maturation of human B cell subsets, we used lineage-specific markers to define immature/transitional (CD10+/CD27–/CD38+/IgD–), transitional (CD10–/CD27–/CD38–/IgDdim), naive (CD10–/CD27–/CD38–/IgD+) and memory (CD10–/CD27+) CD20+ B cells in the blood and spleen of NSG mice that have been implanted with fetal thymic and liver tissues and injected with HSC (Supporting information, Fig. S6). The gating strategy used to define the human B cell subsets is shown in Supporting information, Fig. S6a.

The mean duration of PD survival was 49.2 months in self-care patients, which was significantly longer than the 17.0 months of assisted-care patients (P < 0.05). Using the multivariate Cox proportion regression model to adjust for risk factors, it was found that self-care patients had a lower risk in both patient survival (Hazard Ratio 0.15; 95% confidence interval (CI) 0.2–0.94, P < 0.05) and technique survival (Hazard ratio; 0.11, 95% CI 0.1–0.9, P < 0.05). Fluid overloading was the major cause of technique failure in assisted-care patients. Type of assistance

was not a risk factor for PD-related peritonitis. Our elderly assisted care had patients had a poorer GDC-0973 chemical structure survival and technique survival rates than those of the self-care patients. We argue that this is because early recognition of medical deterioration and early medical intervention are necessary for a better outcome for elderly PD patients. “
“Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary and progressive renal disorder. It is also recognised as the most frequent genetic cause of chronic kidney diseases (CKD). In the present study, four tagging SNPs and two more PS-341 chemical structure well studied polymorphisms (Intron 4 VNTR and Glu298Asp) the NOS3 gene were investigated to unravel the potential

modifier effect of NOS3 gene on the progression of CKD in ADPKD. A total of 102 ADPKD patients and 106 controls were selected for the study. The tagSNPs and Glu298Asp polymorphisms were genotyped using FRET-based KASPar method and intron-4 VNTR by polymerase chain reaction electrophoresis. The genotypes and haplotypes in the controls and ADPKD subjects were analysed by χ2 tests and haploview software. Mantel-Haenszel stratified and

univariate analyses were performed to estimate the influence of different genotypes selleck screening library between different CKD stages and hypertension. The tagSNPs of NOS3 genotypes and haplotypes did not exhibit any significant differences between controls and ADPKD patients. The significant linkage disequilibrium was observed between the rs3918184 and rs2853796 by forming LD block. In univariate analysis, the age and family history of Diabetes mellitus (DM) showed significant association with advancement of CKD, but not with the eNOS polymorphisms. Our data suggests that there is no evidence for the involvement of NOS3 tag SNPs in the progression to CKD in ADPKD patients. A systematic study using well validated functional SNPs is necessary to clarify the role of the NOS3 gene in the development of CKD in ADPKD. “
“Aim:  The present study was conducted to investigate the trends of childhood nephrotic syndrome (NS) admissions and factors associated with childhood NS admissions with major infections in Taiwan.

Hopefully, future studies will help to clarify the potential usefulness of chitin as active component for novel immunosuppressive therapeutic strategies. IL-4 reporter mice (4get mice) were kindly provided by R. M. Locksley (UC San Francisco) 38. These mice carry an IRES-eGFP construct inserted after the stop codon of the IL-4 gene. B7-H1−/− mice were kindly provided by L. Cheng (Johns Hopkins University) 34. TLR2−/−39 and TLR4−/−

mice were obtained from C. Kirschning (TU München). MyD88−/− and MyD88/TRIF−/− mice were obtained from H. Wagner (TU München). TLR3−/− mice were obtained from S. Akira. Stat6−/− mice 40, DO11.10 TCR-tg mice 41 and BALB/c mice were originally obtained from The Jackson Laboratory (Bar Harbour, ME). Single-cell suspensions of spleen and mesenteric LN from Veliparib clinical trial DO11.10/4get mice were prepared and 1×106 TCR-tg cells were transferred into BALB/c recipient mice. One and two days later, mice received intranasal applications of 500 μg OVA (Sigma-Aldrich,

St. Louis, MO) in 50 μL PBS with or without chitin powder (10 mg/mouse). Mice were analyzed on day 5 after T-cell transfer by flow cytometry. Purified chitin from crab shells was used (C9752, Sigma-Aldrich). The colloidal chitin powder is chemically identical to native chitin and was generated by methanesulfonic acid treatment as described previously 42. In total, 10 mg chitin powder or glass beads (10–50 μm; Kisker, Germany) were suspended in 500 μL PBS and left at room temperature for 2 min to allow sedimentation of large particles. The supernatants were collected and washed once with PBS by centrifugation at 14 000 rpm followed by resuspension of the pellet in 500 μL PBS. The suspensions were buy FK506 stored at 4°C until setup of the experiments. The E-toxate test (Sigma-Aldrich) was used to exclude contamination with LPS. Macrophages were differentiated from BM cells in RPMI 1640 (PanBiotech, Aidenbach, Germany) Lonafarnib in vivo supplemented with 10% FCS (Invitrogen, Carlsbad, CA), 2 mM L-glutamine, 100 U/mL penicillin,

100 μg/mL streptomycin (Biochrom AG, Berlin, Germany) and 5×10−5 M β-mercaptoethanol (Merck, Darmstadt, Germany) for 8 days in the presence of 10% supernatant from the M-CSF producing fibroblast cell line L929. Macrophages were scraped off the plates and cultured for 24 h in the presence of chitin- or glass-suspensions which covered about 50% of the surface of the culture plate. Untouched polyclonal CD4+ T cells were isolated by MACS technology (Miltenyi Biotech GmbH, Bergisch Gladbach, Germany) from 4get mice and cultured in 170 μL RPMI 1640 and 10% FCS under neutral (20 ng/mL IL-2) or Th2-polarizing conditions (20 ng/mL IL-2, 10 ng/mL IL-4 and 10 μg/mL anti-IFN-γ (clone XMG1.2)) at 2×106 cells per well in a flat-bottom 96-well plate which had been coated for 24 h at 4°C with anti-TCR (1 μg/mL) and anti-CD28 (1 μg/mL) mAb. Briefly, 30 μL resuspended chitin or glass beads or PBS were added to the cultures which were then analyzed on day 4 by flow cytometry.

For this reason, methods of abrogating the activity of Treg cells might be critical for the successful immunotherapeutic treatment of cancer. Studies showed that Treg and Th17

cells co-existed in the microenvironment of different types of tumour, and the development of Th17 cells was described to be linked to that of Treg in a reciprocal fashion; however, information on human bladder cancer Th17/Treg development and differentiation is limited. Our data revealed that Th17 cells were correlated inversely with Treg cells and correlated positively with IFN-γ+ CD4+ T cells in the same tumour microenvironment. It has shown that recombinant IL-2 is a promising agent for the activation of immune response against tumour click here and plays a central role in balancing Treg cells and IL-17+ T cells in multiple diseases. Kryczek et al. reported that IL-2 regulated JAK assay the balance between tumour Treg and Th17 cells by stimulating the differentiation of Treg and inhibiting that of Th17 cells [35]. However, Leveque et al. revealed that under some stimulated conditions, IL-2 rapidly converted epithelial ovarian cancer (EOC) Treg into Th17 cells, down-regulated

FoxP3 expression, and lost their suppressive capacity [17]. Due to the above conflicting data, we sought to determine whether IL-2 would also play a role in balancing Treg cells and IL-17+ T cells in bladder cancers. Our results indicated that tumour-infiltrating Treg cells cultured in the presence of the autologous irradiated CD3– fraction and IL-2 could be converted into Th17 cells, which might be involved in the mechanism that instillations of IL-2 into the urinary bladder is effective in the treatment of superficial bladder cancer. In conclusion, the present data suggest that Th17 cells, together with Treg cells, might contribute to the immunopathogenesis of bladder cancer, and inhibition of Th17 cell development might be a novel immune evasion mechanism. We further identified NADPH-cytochrome-c2 reductase that IL-2 played a role

in balancing Treg cells and IL-17+ T cells by converting bladder cancer Treg into Th17 cells, our results encouraged a deep in vivo exploration of its effects on in situ immune responses. Further studies are still needed to identify the mechanisms of underlying regulation and dynamic interaction among Th17 cells and Treg and Th1 cells in human pathological conditions such as bladder cancer. The authors have no financial conflict of interest. This study was supported by Heilongjiang Province Science Foundation for Youths (project number: QC2009C05), China Postdoctoral Science Foundation, Innovation of science and technology of Harbin youth (project number: 2008RFQXS008) and Foundation of Heilongjiang Educational Committee (project number: 11531160).

In the late referral group, 15 patients required commencement of dialysis via a temporary

central venous access, pulmonary oedema was present in 13 patients and malignant hypertension was present in three patients. The later referral group was characterized by more severe biochemical and haematological markers of uraemia such as higher serum creatinine and phosphate concentrations and lower creatinine clearance, serum bicarbonate, calcium and haemoglobin. Systolic and diastolic blood pressures were also significantly higher in the late referral group. The duration of hospitalization (33.2 ± 13.1 days vs 5.7 ± 1.1 days, P < 0.001) and the cost of hospitalization were significantly higher in the late referral group. Ellis et al. in 1998 reported a retrospective find more review of all patients who developed ESKD and who were accepted for renal replacement therapy (RRT) at Kings College, London over a 2-year period from 1 January 1996 to 31 December 1997.33 Sixty-four patients were regarded as late referral (<12 weeks prior to commencing RRT) and 134 patients were classified as early referral (>12 weeks prior to starting RRT). In the late referral group, there was objective evidence of renal disease for at least

Dasatinib clinical trial 8 weeks in 50% of patients and 22% of patients had evidence of renal disease for at least 1 year prior to the time of referral. Suboptimal management of CKD prior to referral to the nephrology service was common. Only 33% of diabetic patients were treated with an angiotensin-converting enzyme inhibitor and 49% of patients with CKD and hypertension had inadequate control of blood pressure at the time of referral to the nephrology service. The length of hospitalization was significantly longer in the late referral group (25 vs 9.7 days, P < 0.001). However, there was no difference in mortality between the early and late referral groups (12-month survival: Casein kinase 1 60.5% vs 72.5%). Khan et al. in 1995 reported factors associated with early mortality on dialysis in a retrospective,

case–control study of patients being dialysed at a single centre in Aberdeen (UK) between 1 January 1971 and 6 January 1993.34 Forty-two patients who died within 90 days of the commencement of haemodialysis were compared with age- and sex-matched patients who survived longer than 90 days. In the early mortality group, there were a higher proportion of patients who required urgent dialysis (79% vs 21%, P < 0.05) and there was a shorter period of predialysis management (1.1 vs 10.6 months, P < 0.0001). A greater prevalence of arteriolosclerosis, comorbid illness and smoking and a lower mean serum albumin (31.4 vs 37.1 g/L, P < 0.006) were also identified in the early mortality group. A similar experience was reported by Innes et al. in a retrospective analysis of 44 patients who died within 1 year of starting dialysis compared to 44 age- and sex-matched patients who survived more than 1 year.

17 Conversely, GSI-IX concentration the 2A peptide linker results in a single mRNA molecule, but during translation ribosomal skipping generates two separate proteins from the single mRNA.18 The majority of constructs currently in clinical and preclinical development use the 2A sequence to link the TCR-α and TCR-β chains as a result of the improved equimolar expression of both genes, compared to vectors with an IRES element separating the TCR genes. Importantly, it has been shown by ourselves and others that T cells transduced with constructs containing the TCR genes linked by a 2A sequence express higher levels of cell-surface TCR and demonstrate improved antigen-specific function, as measured by IFN-γ secretion,

compared with constructs containing identical TCR sequences

separated by an IRES element.19 Efficient cell-surface TCR expression requires the formation of a stable TCR–CD3 complex.11 In Neratinib mouse the absence of CD3, TCRs do not assemble properly and are degraded. Therefore, the availability of CD3 molecules for TCR–CD3 complex assembly is a major rate-limiting effect when introducing additional exogenous TCRs into T cells. Competition may reduce cell-surface expression of the introduced TCR and impair the avidity of antigen recognition of the transduced cells. We have recently demonstrated that the double transduction of CD8+ T cells with a vector encoding the desired TCR-α and TCR-β chain genes, together with a second vector encoding the CD3 gamma, delta, epsilon and zeta genes (linked by 2A sequences), can enhance the avidity of CD8+ T cells (King J, Ahmadi M, personal communication). This may be a mechanism to enhance the functional avidity of transduced T cells expressing low-affinity TCRs. It is common for the introduced TCRs to be expressed at lower levels than the endogenous TCRs, which may impair the ability of the transduced T cell to respond to low concentrations of the TCR-recognized antigen, as

discussed above. This observation is consistent with the introduced TCR competing with the endogenous TCR for limited CD3 molecules. Heemskerk et al.20 old have recently shown that the expression levels of the introduced TCR can be influenced by the ‘strength’ of the endogenous TCR by introducing the same TCR into different antigen-specific T-cell clones. It is currently unclear whether TCR-specific molecular motifs exist to determine the ‘competitiveness’ of a given TCR-αβ chain. Primary T cells transduced with exogenous TCRs have the potential to express four different TCR-αβ heterodimers on the recipient T-cell surface: (i) the endogenous αβ heterodimer; (ii) the introduced αβ heterodimer; (iii) the endogenous α chain paired with the introduced β chain; and, finally, (iv) the introduced β chain paired with the endogenous α chain. These possibilities are indicated in the schematic diagram shown in Fig. 2.

In the recent year, timing for initiation of dialysis in advance CKD patients has been discussed widely, and there is a trend of not to dialysis patient solely depends GSI-IX datasheet on the level of GFR or serum creatinine. If patients have no life-threatening condition or without major uremic symptom/sign, it is suggested dialysis could be delayed. In Taiwan, it has been a rule to initiate dialysis at a very low level of GFR, no matter due to Insurance regulation or patient’s willing. Our unique experience in dialysis initiation could provide more information for other countries. LIEW ADRIAN Department of Renal Medicine,

Tan Tock Seng Hospital, Singapore As a renal replacement therapy, renal transplantation confers the best survival advantage over dialysis for the patient with end-stage renal disease (ESRD)1. The transplantation of these patients prior to the initiation of dialysis therapy, known widely as preemptive renal transplantation, offers the advantage of avoiding the complications, morbidities, and infrastructure and manpower

costs associated with dialysis access and therapy. The further argument for preemptive transplantation stems PLX3397 price from the unfavorable death rates among waitlisted patients compared with transplant recipients2. Indeed, large analyses of registry data, albeit retrospective in nature, had demonstrated that preemptive renal transplantation leads to considerable improvements in allograft and patient survival2,3, when compared to transplantation after a period of dialysis therapy. In fact, with incremental time on dialysis, the risk of graft loss and patient death after transplantation had been shown to increase linearly4. While the exact reasons for these improved outcomes with preemptive renal transplantation had not been clear, several observations had been made that could provide some information towards the contributing factors. Delayed graft function and biopsy-confirmed acute buy CHIR-99021 rejection are well known to have negative effects on graft survival, and the association of preemptive transplantation with

lower rates of these occurrences5 could contribute to its superior outcomes noted in these large analyses. The low solute clearances associated with dialysis therapy expose patients to risks of accelerated atherosclerosis, malnutrition and chronic inflammation, which are adverse outcomes that can be avoided with preemptive transplantation5. Preemptive transplant recipients have also been found to have socioeconomic and demographic features that predict better outcomes, namely younger age, higher educational background, economic viability and fewer HLA antigen mismatches3,6. Furthermore, it had also been implied that preemptive transplantation alone could have direct beneficial effects on graft survival. The precise timing to proceed with preemptive transplantation remains controversial.

By excluding the results of the filariasis samples, the

specificities of the IgG4- ELISA and both of the IgG-ELISAs increased to 100% and EPZ015666 solubility dmso 98%, respectively. Thus, although the IgG4-ELISA is less sensitive than the IgG-ELISAs, the former is more specific. To determine whether the cross-reactivity with filariasis patient sera was influenced by the abundance of antifilarial antibodies, titrations of IgG4 were performed on the filariasis patient serum samples, followed by an analysis of the correlation with the results of the Strongyloides IgG4-ELISA (Figure 3). The two parameters were found to be weakly correlated (Spearman rho = 0·4544; P = 0·0294). Although previous investigators had reported cross-reactivity between strongyloidiasis and filariasis [4, 13, 27], this selleck kinase inhibitor study demonstrated that the binding of the Strongyloides antigen to the antifilarial antibodies was not much influenced by the titre of the latter. It is thus highly recommended that, in filariasis endemic area, positive serological cases of strongyloidiasis should also be tested for filariasis before confirming the serodiagnosis. For brugian filariasis, a commercially

available test called Brugia Rapid (Reszon Diagnostics International Sdn. Bhd., Selangor, Malaysia) can be used to assist with this differential diagnosis because the test has been shown to be highly specific (>95%) when tested with serum samples from patients with strongyloidiasis [28, 29]. In this regard, a 31-kDa Strongyloides recombinant antigen (NIE) has been reported to be specific against antibodies to nonlymphatic and lymphatic filariasis [27, 30, 31] and thus is potentially useful as a diagnostic reagent. In conclusion, because the detection of parasite-specific IgG4 antibodies is more specific but less sensitive than the detection of parasite-specific IgG antibodies, the combined use of IgG and IgG4 assays would be helpful in improving the serodiagnosis of strongyloidiasis.

Efforts to develop field-applicable rapid tests using recombinant antigen(s) that do not cross-react with antibodies to lymphatic and nonlymphatic filaria should be encouraged. This study was funded by Universiti Sains Malaysia Research University grant, No: 1001/CIPPM/812078 Dichloromethane dehalogenase and USM short-term grant No. 304/PPSP/61312089. We gratefully acknowledge the contributions of Madihah Basuni and Dr Khoo Boon Yin in this study. “
“This study aimed to examine the frequency of different subsets of circulating B and T follicular helper (Tfh) cells in patients with new-onset rheumatoid arthritis (RA) and following standard therapies. Twenty-five RA patients and 15 healthy controls (HC) were recruited for characterizing the frequency of CD27+, immunoglobulin (Ig)D+, CD86+, CD95+, Toll-like receptor (TLR)-9+ B cells and inducible T cell co-stimulator (ICOS) and programmed death 1 (PD-1)-positive Tfh cells and the level of serum interleukin (IL)-21.

When the anti-BTLA reagents were co-immobilized on the plate

with the learn more stimulus, no significant effect on T cell proliferation was observed. However, when the anti-BTLA reagents were putatively ‘cross-linked’ by coating the plate with a polyclonal goat anti-mouse Fc reagent and then adding the murine reagents, the mHVEM-mFc ligand and some of the anti-BTLA mAb inhibited T cell proliferation dose-responsively – specifically, clones 6 H6, 8F4 and 3F9.D12. A similar effect was seen on the levels of secreted interferon-γ (data not shown). Further studies with the anti-BTLA reagents in the murine in vitro MLR and the murine in vitro DO11.10 antigen-specific T cell proliferation system have shown similar results to the direct plate immobilization assay system in that the anti-BTLA reagents had no significant effect on in vitro T cell proliferation induced by these methods (see Supporting information, Figs S1 and S2, at the end of the paper and online). Competition binding experiments with surface plasmon resonance (BIAcore) showed that the CH5424802 clinical trial anti-BTLA mAb clones that inhibited in vitro T cell proliferation in the ‘cross-linked’ plate format grouped to a similar

epitope on the BTLA molecule and, conversely, the clones that had no effect on T cell proliferation grouped to a different epitope (see Fig. S3). Figure 2 shows the effect of anti-BTLA reagents on the LPS-induced or anti-CD40 plus anti-IgM mAb-induced proliferation of murine spleen derived B cells in vitro. Neither method of induced in vitro B cell proliferation was affected significantly by PJ34 HCl anti-BTLA antibodies or mHVEM-Fc. No significant inhibition of proliferation was detected with co-immobilized

(see Fig. 2) or cross-linked anti-BTLA reagents (data not shown), nor did we see any effect on the lower levels of proliferation induced by an anti-IgM mAb alone (data not shown). Notably, none of the clones that inhibited in vitro T cell proliferation had any significant effect on B cell proliferation induced by any of the above methods. In an effort to elucidate further the exact mechanism of how the mHVEM-mFc ligand and some of the anti-BTLA mAbs acted to inhibit T cell proliferation, we used a beads-based approach in addition to direct immobilization on polystyrene plates. Figure 3 shows that, similarly to direct immobilization in the plate, bead-absorbed anti-CD3ε mAb caused T cell proliferation. Some of the anti-BTLA reagents that had been shown previously to inhibit T cell proliferation were tested in this novel format – specifically the mAb 6H6 and the mHVEM-mFc ligand, as well as an isotype control antibody. The test reagents were immobilized on either the same bead as the stimulus (cis format) or a different bead (trans format). Only anti-BTLA reagents in the cis, and not the trans, format relative to the activating stimulus inhibited this T cell proliferation.

The distribution of alleles in HIV-1 infected Japanese was similar to that of the general Japanese population described above (data not shown). We then compared the level of pVL in terms of presence or absence of individual class I alleles (Table 1), and found that five alleles (HLA-A20, B07, B54, Cw01 find more and Cw15) were associated with lower or

larger pVL, (P < 0.05 by Fisher's exact probability test). However, after determining q-values (20) none of the associations remained significant, indicating that there are no strongly protective or detrimental alleles in this unique Asian population. Notably, in this cross-sectional analysis, expression of HLA-B51, which is the third most beneficial allele after B57 and B27 in Caucasians (7, 22), proved to be not at all protective in Japan; likewise, HLA-A11, A26 and Cw14, which have also been reported to be protective

in the USA in a study which controlled for ethnicity (7), did not show any protective effects in Japanese, either. Taken together, these results indicate that alleles which have protective effects in a given population do not necessarily behave similarly in other populations. An HLA supertype is defined as a group of class I alleles sharing a similar peptide binding motif, thereby being able to present the same CTL epitopes (23). Some HLA class I supertypes have been reported to be MG-132 cost associated with pVL in the USA: (B7s with larger pVL, and B27s/B58s with lower pVL) (24). We looked for such associations in the Japanese population by classifying alleles observed in our cohort into eight supertypes according to the literature (i.e., A1s, A2s, A3s, A24s, B7s, B27s, B44s, B62s) (23), and found that there were no significant associations between level of pVL and expression of particular class I supertypes in the Japanese population (data not shown). This finding may be due to the Japanese lacking HLA-B27/B57, which are major contributors to the protective supertypes in the USA (24). We further assessed the

impact on pVL of the Bw4/Bw6 motif of HLA class I molecules, which are known to act as ligands of KIR on natural killer cells and to modulate their activity (25, 26). Homozygosity for Bw6 motif has been reported to be associated with rapid disease progression, Interleukin-2 receptor whereas the subtype of Bw4, which is carried by various alleles including HLA-B27/B57, is associated with slow disease progression (27, 28). However, there was no difference in the level of pVL between Bw4 and Bw6 homozygotes in the Japanese population (median: 26 000 vs. 20 500 RNA copies/ml, P= 0.976, Fig. 2), indicating that the findings reported from the USA cannot reliably be extended to other populations. In the cross-sectional analyses, we did not find any associations between the level of pVL and expression of individual class I alleles, supertypes or Bw motifs in this unique Asian population.