HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10^?3).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival

BackgroundThe essential function of B cell–activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood.MethodsObjective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival.ResultsPretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262 ± 2796 pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252 ± 1425 pg/ml; p < 0.0001). In addition, pretransplant BAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r = 0.2966, p = 0.0025). Patients with high pretransplant BAFF levels (≥ 2137 pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p = 0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p = 0.02), presence of anti-HLA antibodies (RR 2.5; p = 0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p = 0.003) before transplant and AMR post transplant (RR 2.5; p = 0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p = 0.03).ConclusionElevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR.     

Antibody response to HBV vaccination on dialysis does not correlate with the development of deNovo anti-HLA antibodies after renal transplantation

BackgroundResponse to Hepatitis B virus (HBV) vaccination can be diminished in some (50–80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to predict alloresponses.MethodsThe response to HBV vaccination on dialysis and the development of deNovo anti-HLA antibodies post-transplant was analyzed in 188 non-immunized renal transplant recipients. The response to HBV vaccination was evaluated by measuring the anti-HBs titer at time of transplantation. Anti-HLA antibodies post-transplant were monitored by serial measurements by means of Luminex. Acute rejection episodes, graft loss and renal dysfunction were assessed within a median follow-up of 5.5 years.ResultsOne hundred and forty-one patients (75%) exhibited an adequate immune response to HBV vaccination on dialysis. Vaccine responder (R) and none responder (NR) did not differ with respect to age, gender and BMI, while R spend significantly more time on dialysis before transplantation (4.58 ± 3.35 vs 3.23 ± 2.55 years, p = 0.033). More NR developed deNovo anti-HLA antibodies (27.7 vs 22.7%, p = 0.554) and donor-specific anti-HLA antibodies (23.4 vs 14.2%, p = 0.173) in comparison to R. Accordingly, the number of acute rejections was higher in NR as compared to R (36.1 vs 24.1%, p = 0.130) while graft survival was similar in both groups.ConclusionContrary to our hypothesis antibody response to HBV vaccination on dialysis does not predict the development of anti-HLA antibodies post transplant.     

Repeated human leukocyte antigen mismatches in lung re-transplantation

BackgroundThe role of HLA-sensitization in the absence of detectable DSA in lung re-transplantation is unclear. Antigens of the second donor matching the HLA typing of the first donor are considered ‘unacceptable’, by some tissue typing laboratories, especially in kidney re-transplantation.MethodsThus, we performed a retrospective analysis of all lung re-transplantations focussing on the impact of HLA-homologies between the first and the second donor (‘unacceptable’ antigens; repeated HLA mismatch) on patient and graft survival.ResultsA total of 132 lung re-transplantations were performed at our centre between 1985 and 2014, of which 120 with complete HLA data were analysed. 55.8% of the recipients received re-transplants with repeated HLA mismatched antigens whereas 43.2% of the re-transplants were transplanted without repeated HLA mismatched antigens.Postoperative survival showed no difference between re-transplant procedures with or without repeated HLA mismatches (p = 0.99). While neither homologies on the HLA-A, -B, -C, or -DR locus, nor the addition of several locus homologies (p = 0.72) had an impact on survival, unexpectedly, repeated HLA mismatching on the HLA-DQ locus was correlated with better survival. Re-transplantations with repeated HLA mismatches did not result in more development of CLAD as compared to recipients without repeated HLA mismatches (p = 0.99). Neither the number of repeated HLA mismatched antigens (p = 0.52) nor the HLA locus (HLA-A(p = 0.34), HLA-B(p = 0.97), HLA-C (p = 0.80), HLA-DR(p = 0.49) and HLA-DQ(p = 0.07)) had an impact on the development of CLAD after re-transplantation.ConclusionTransplantation with repeated HLA mismatches due to sensitization by a previous transplantation in the absence of detectable HLA-antibodies does not have a negative impact on patient or graft survival.     

The impact of pregnancy on rheumatoid arthritis outcome: The role of maternofetal HLA class II disparity

ObjectivesTo investigate the influence of pregnancy and postpartum on rheumatoid arthritis (RA) course and the impact of maternofetal HLA class II disparity.MethodsIn 13 women with RA, disease activity was assessed prospectively, before and every three months throughout pregnancy and after delivery until one year in postpartum. The HLA class II disparity was evaluated by typing HLA–DRB1, DQB1 and DQA1 alleles by the PCR-SSOP for 12 couples mothers and babies. Furthermore, for three women, RA disease activity during a previous pregnancy was evaluated retrospectively and HLA typing was performed for the three children.ResultsThe mean age of patients was 30 ± 5 years. All women had successful pregnancy. During pregnancy, a favourable RA outcome was noted in 62.5% of cases. Three patients were in remission after conception. Persistent disease activity was noted in 30% of cases. In postpartum, disease relapse occurred in 92% of cases at a mean delay of 80 ± 63 days. Three women did not resume the initial modifying antirheumatic drugs (DMARDs) 12 months after delivery. For others, the mean delay was 6 ± 3.5 months. There was no significant correlation between the clinicoradiological parameters and the RA outcome. We noted a tendency towards correlation between male newborns and an unfavourable RA outcome (p = 0.059). A high degree of maternofetal disparity in HLA class II was seen in 73.5% of cases. We observed a more marked improvement in disease activity parameters in case of more than one disparity but without a significant statistical difference.ConclusionA favourable RA outcome during pregnancy in about two-thirds of the cases and a frequent relapse after delivery were observed. RA activity improvement is more obvious at the end of pregnancy. A high degree of maternofetal HLA class II disparity seems to modulate RA disease activity.     

HLA association with the susceptibility to anti-synthetase syndrome

ObjectiveTo investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD).MethodsWe conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing.ResultsA statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed.ConclusionsOur results support the association of the HLA complex with the susceptibility to ASSD.     

Oncological outcomes of laparoscopic nephroureterectomy with pluck method for distal ureter resection

ObjectiveTo report the oncologic outcomes of upper tract urothelial carcinoma treated with laparoscopic nephroureterectomy and pluck method for distal ureter resection.Materials and methodsBetween May 2004 and November 2015, 118 patients with upper urinary tract urothelial carcinoma received laparoscopic radical nephroureterectomy with endoscopic bladder cuff excision at our institution. The medical records were reviewed retrospectively for clinical and pathological results. Cox regression analyses were performed on factors related to oncological outcomes.ResultsThe median follow-up was 26 months. Bladder recurrence was found in 27 patients (22.9%), extravesical retroperitoneal recurrence in four patients (3.4%), and metastases in 17 patients (14.4%). Multivariate analyses showed that male sex was associated with higher bladder recurrence [odds ratio (OR) = 2.2; 95% confidence interval (CI), 1.02–4.78; p = 0.045)], tumor size had significant correlation with locoregional recurrence (OR = 1.29; 95% CI, 1.07–3.43; p = 0.029), tumor stage was significantly correlated with subsequent metastasis (OR = 2.08; 95% CI, 1.21–3.56; p = 0.008) and overall survival (OR = 1.84; 95% CI, 1.06–3.22 ; p = 0.031), and tumor size correlated significantly with cancer-specific survival (OR = 2.57; 95% CI, 1.16–5.72; p = 0.021).ConclusionsTumor size and tumor stage were significantly associated with survival (cancer-specific and overall survival) in patients receiving nephroureterectomy with pluck method.     

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population

IntroductionCytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility.Material and methodsA case–control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk.ResultsWe observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01–0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01–0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01–0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01–0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13–2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15–2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09–1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (A_rs11207535C_rs10889159T_rs1155002 and A_rs11207535C_rs10889159C_rs1155002) significantly decreased COPD risk.ConclusionIt suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.     

The impact of serum albumin and serum protein levels on POSSUM score of patients with proximal femur fractures

BackgroundPOSSUM was developed to predict risk-adjusted mortality and morbidity rates for surgical procedures. We evaluated the impact of serum albumin and serum protein levels on POSSUM scores.MethodsMedical files of 2269 patients operated for proximal femur fractures were reviewed. Preoperative serum albumin levels were available for 387 patients (mean 35.1 g/l, range 22–49) and serum protein levels for 279 patients (mean 61.6 g/l, range 40–86).ResultsSerum albumin and protein levels were inversely associated with mortality in multivariate models (albumin, OR = 0.89, p = 0.009; protein, OR = 0.92, p = 0.009) and in composite outcome models as well (albumin, OR = 0.955, p = 0.219, protein, OR = 0.94, p = 0.014). The area under the curve (AUC) for POSSUM prediction of mortality (n = 1770) was 0.632 (95% CI: 0.580–0.684, p < 0.001). The AUC for a model including serum protein levels was 0.742 (95% CI: 0.649–0.834, p < 0.001). Hospitalisation time was longer for patients with lower serum proteins levels (p = 0.045), with an inverse correlation (Pearson correlation −0.164, p = 0.011).ConclusionsLower preoperative serum albumin and serum protein levels were associated with increased risk for mortality, increased hospitalisation time and poorer outcomes in patients operated for proximal femoral fractures. Including those values to POSSUM scores would increase their predictive power.     

Detection of plasma cells,C4d deposits and donor-specific antibodies on sequential graft biopsies of renal transplant recipients with chronic dysfunction

BackgroundIn order to look for a relationship between humoral mechanisms of rejection and chronic allograft dysfunction, plasma cells, C4d deposits and donor-specific antibodies (DSA) were simultaneously sought on serial biopsies of kidney allograft recipients.Patients and methodsTen recipients with chronic dysfunction (G1) and 8 recipients with long-term normal graft function (G2) were included. Biopsies and serums were sampled at early graft dysfunction (T1), between 8 months and 2 years (T2) and after the third year following transplantation (T3).ResultsIn G1, plasma cells represented 12.3% (T1), 8.2% (T2) and 14.1% (T3) of mononuclear cells. The mean percentage of plasma cells was 11.6% in G1 versus 0.4% in G2 (p < 0.05). A progressive rise in C4d deposits was seen in G1, from 25% at T1 to 80% at T3. Donor-specific antibodies were identified in at least one serum sample of 60% of the patients in G1 and 12.5% of the patients in G2 (p = 0.012), whereas donor-specific antibodies were eluted from at least one biopsy of 50% of the patients in G1 and 12.5% of the patients in G2 (p = 0.03). In G1, C4d deposits were significantly associated with plasma cells (p = 0.0012) and anti-HLA Abs in serum samples and/or eluates (p = 0.026).ConclusionThis study shows that plasma cells, DSA and C4d are associated in renal transplants developing chronic rejection.     

Clinical risk factors associated with the post-transplant anemia in kidney transplant patients

BackgroundAnemia is a very common occurrence in post-renal transplant patients. Post-transplantation anemia (PTA) is associated with significant graft loss or cardiovascular morbidity. The objective of this study is to identify clinical risk factors associated with anemia after kidney transplantation.MethodsOur retrospective cohort study included a total of 570 renal transplant recipients. For the definition of anemia, we adopted “the lower limit of normal for Hgb concentration of blood” proposed by Beutler E and Waalen J [14], which has adjustments for age, gender and ethnicity. Post-transplant anemia (PTA) was defined as anemia that arose between 30 and 180 days after transplantation. Based on this definition, of the 570 renal transplant recipients, 344 patients (62.1%) experienced PTA. The patients were divided into anemic and non-anemic groups, and a total of 20 clinical factors were compared between the two groups.ResultsIn the univariate analysis, age, race, multiple transplants, delayed graft function (DGF), and use of tacrolimus, sirolimus, thymoglobulin, ganciclovir, ACE inhibitors, and ARBs were associated with PTA. In the multivariate analysis, age (> 60 years old, OR = 2.62, p = 0.001), race (OR = 2.54, p = 0.001), and use of sirolimus (OR = 2.01, p = 0.019), antiviral agents (OR = 1.96, p = 0.015), thymoglobulin (OR = 1.86, p = 0.011), and DGF (OR = 2.78, p = 0.001) remained significant.ConclusionThe current results show that undergoing a transplant at age 60 or older, use of sirolimus, antiviral agents, and thymoglobulin are independent clinical risk factors associated with PTA. In terms of ethnicity, AA, MEA, or PI is higher risk for PTA and Hispanic is significantly lower risk for PTA compared to Caucasians.     

Survey of nulliparous parturients' attitudes regarding timing of epidural analgesia initiation

Study objectiveAt our hospital, although > 90% of nulliparous parturients eventually choose epidural analgesia for labor, many delay its initiation, experiencing considerable pain in the interim. This survey probed parturients' views about the timing of initiation of epidural labor analgesia.DesignSingle-center, nonrandomized quantitative survey.SettingLabor and delivery suite in a large tertiary academic medical center.PatientsTwo hundred laboring nulliparous women admitted to the labor and delivery suite.Interventions: After their pain was relieved, parturients completed a questionnaire regarding their decision to request labor epidural analgesia.MeasurementsA variety of factors regarding epidural use were assessed including the influence of painful contractions and of childbirth education class attendance on the decision to request epidural analgesia, and parturients' perception of the timing of epidural initiation on the progress and outcome of labor.Main resultsAnalysis revealed that the desire of parturients to use epidural analgesia was increased from 27.9% before the onset of painful contractions to 48.2% after (p < 0.01). Two-thirds of participants attended a non-physician taught childbirth education class. An antepartum plan to definitely forgo an epidural was 1.8 times more likely among women who attended a childbirth class when compared to those who did not attend. (OR = 1.8; 95%CI:1.1–3.1; p = 0.04). The most common views affecting decision-making were that epidural analgesia should not be administered “too early” (67.5%), and that it would slow labor (68.5%). Both of these views were more likely to be held if the parturient had attended a childbirth class, OR = 2.0 (95%CI:1.1–3.8; p = 0.03) and OR = 2.0 (95% CI: 1.1 to 3.7; p = 0.03), respectively.ConclusionsWe found that nulliparous parturients have misconceptions about epidurals, which are not supported by evidence-based medicine. Moreover, we found that attendance at childbirth education classes was associated with believing these misconceptions.     

The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes

BackgroundNon-HLA antibodies (Abs) targeting vascular receptors are considered to have an influence on renal transplant injury. Anti-endothelin-1 type A receptor (anti-ETAR) antibodies were associated with cellular and antibody-mediated rejection and early onset of vasculopathy in heart transplant patients but their role in renal transplantation remains unclear. The aim of our study was to assess the incidence and importance of anti-ETAR antibodies and their impact on renal transplant during the first year observation.MethodsWe evaluated the presence of anti-ETAR antibodies in 116 consecutive renal transplant recipients in pre- and post-transplant screening (before and in 1st, 3rd, 6th, 12th month after transplantation). Additionally, we assessed the presence of anti-HLA antibodies. Anti-ETAR antibodies were assayed by ELISA. The diagnosis of acute rejection was based on the Banff criteria.ResultsAnti-ETAR antibodies were observed in 55 (47.4%) of the analyzed recipients before transplantation. The function of renal transplant was significantly worse in the anti-ETAR(+) group compared to the anti-ETAR(?) group during the first post-transplant year. One month after transplantation the serum creatinine in anti-ETAR (+) patients (pts) was 1.86 ± 0.8 mg/dl and 1.51 ± 0.5 in anti-ETAR(?) pts (p = 0.009). Twelve months after transplantation the difference between the groups was still observed 1.70 ± 0.7 vs. 1.40 ± 0.4 (p = 0.04).Biopsy proven acute rejection was recognized in 8/55 (14.5%) in ETAR(+) and 9/61 (14.8%) in ETAR(?) patients but cases with mild to severe intimal arteritis (v1–v3) were more often observed in patients with the presence of anti-ETAR Abs 4/55 (7.2%) comparing with 1/61 (1.6%) in anti-ETAR(?) patients. The anti-ETAR antibody levels varied at different measurement intervals during the one-year follow-up.ConclusionsThe presence of anti-ETAR antibodies is associated with a worse renal transplant function during the first 12 months after transplantation. Including anti-ETAR antibodies in the diagnostics of renal transplant recipient immune status should be considered to provide comprehensive assessment of humoral alloimmunity.     

HLA polymorphism and early rheumatoid arthritis in the Moroccan population

ObjectivesRheumatoid arthritis (RA) is an autoimmune multifactorial disease which has a great socio-economic impact in Morocco. The association of HLA genes with RA was studied in various ethnic groups but not in the Moroccan population. Our study focused on evaluating the distribution of class I and class II HLA genes among Moroccan patients presenting early signs of RA.MethodsForty nine patients diagnosed with early RA were compared to a group of healthy controls matched by age, sex, and ethnic origin. Among the patient group, 34 were seropositive (presence of the rheumatoid factor). HLA typing of the patients and the controls was performed using microlymphocytotoxicity for class I (A and B) and PCR-SSP for class II (DR and DQ).ResultsWe found a significant increase of the frequency of the HLA-A24 antigen (p = 0.03), the DRB1*04 (p = 0.004) and DQB1*03 (p = 0.03) alleles and a significant decrease of the DRB1*07 allele (p = 0.03) in seropositive patients. The analysis of the frequency of the DRB1*01, DRB1*10, and DRB1*14 alleles did not show any difference between the RA patients and the controls. The frequency of DR4-DQ2 and DR4-DQ4 haplotypes was increased in the patients compared to the controls while that of DR7-DQ2 and DR13-DQ6 was decreased.ConclusionsOur study suggests that DRB1*04 predisposes to RA while DRB1*07 seems protective for the Moroccan patients population. In addition we show the influence of some haplotypes DR-DQ in the susceptibility and protection against the disease.     

Mannose-binding lectin-2 and ficolin-2 gene polymorphisms and clinical risk factors for acute rejection in kidney transplantation

IntroductionThere is growing evidence that the lectin pathway is significantly associated with acute rejection. Rare studies associated both gene polymorphisms of MBL2 and FCN2 with acute rejection after kidney transplantation. The aim of the present study was to investigate the role of the lectin gene profile and clinical risk factors such as PRA level on acute rejection in kidney transplant recipients.MethodsWe prospectively analyzed 157 kidney transplant recipients with and without acute rejection. A total of 6 well-known functional single-nucleotide polymorphisms in the MBL2 gene and 5 in the FCN2 gene of the recipients were determined by gene sequencing. MBL2 and FCN2 genotypic variants were analyzed for association with the incidence of acute rejection within the first year after kidney transplantation.ResultsAfter adjusting for variables of P < 0.2, we found the differences in the incidence of acute rejection were only according to panel-reactive antibodies (odds ratios (OR) = 6.468, 95% confidence intervals (CI) = 2.017–20.740, P = 0.002) and the HH genotypes of MBL2 promoter ? 550 (OR = 2.448, 95%CI = 1.026–5.839, P = 0.044).ConclusionPanel-reactive antibodies and the HH genotypes of MBL2 promoter ? 550 have significant impacts on the risk of developing acute rejection after kidney transplantation.     

Midfoot plantar pressure significantly increases during late gestation

BackgroundA rise in plantar pressure has been observed in pregnant women with foot pain. The current literature on plantar pressure in pregnancy is sparse. It has been postulated that changes in plantar pressure result from the physiological effects of pregnancy. In this study we aim to quantify the plantar pressure of women in late pregnancy.MethodsTwenty-two pregnant women undergoing a caesarean section and twenty non-pregnant women were recruited from University Hospital Coventry and Warwickshire between May to June 2007. Plantar pressure measurements were performed using an in-shoe measurement system. The control group was compared with the pregnant group at 38 weeks gestation. A selection of the pregnant group had repeat measurements at 4 months post-partum. The pre and post-partum measurements were also compared.ResultsThe pregnant group (PG) exerted a significantly higher mean midfoot pressure compared to the non-pregnant control group (CG) (PG = 115.5 kPa, CG = 95.4 kPa; p = 0.001).Post-partum (PP), there was a significant reduction in the mean and maximum midfoot pressure (mean; PG = 111.9 kPa, PP = 66.2 kPa; p < 0.001, maximum; PG = 184.0 kPa, PP = 108.3 kPa; p < 0.001).ConclusionsThe physiological changes in late pregnancy result in an increase in midfoot plantar pressure. This increase resolves post-partum.     

Ibrutinib suppresses alloantibody responses in a mouse model of allosensitization

BackgroundIbrutinib is a Bruton's tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling. Complete BTK deficiency is associated with absence of B-cells. Ibrutinb is currently approved by FDA for treatment of B-cell malignancies, including Waldenström macroglobulinaemia. We recently carried out studies to determine if ibrutinib could modify alloantibody responses.Materials and methodsA mouse model of allogenic sensitization using a C57BL/6 mouse as the recipient of a skin allograft from an HLA-A2 transgenic mouse was utilized to examine the effects of ibrutinib on alloantibody responses and B cell effector functions. Donor-specific antibody (DSA) levels were measured in a flow-cytometric antibody binding assay. Splenic T and B cell subsets and plasma cells were analyzed in flow cytometry.ResultsControl mice developed peak levels of DSA IgM at day 14 PTx while the ibrutinib treated mice had significantly lower levels of DSA IgM (p = 0.0047). Control mice developed HLA.A2-specific IgG antibodies at day 14 (230 ± 60 MFI) and reached peak levels at day 21 (426 ± 61 MFI). In contrast, mice in the treatment group had low levels of HLA.A2-specific IgG at day 14 (109 ± 59 MFI, p = 0.004) and day 21 (241 ± 86 MFI, p = 0.003). FACS analysis found a reduction of B220⁺ or CD19⁺ B cell population (p < 0.05). In addition, ibrutinib attenuated recall DSA IgG responses to re-sensitization (p < 0.05) and reduced CD38⁺ CD138⁺ plasma cells (p < 0.05) in the spleens.ConclusionsIbrutinib is effective in suppressing alloantibody responses through blocking BTK-mediated BCR signaling, leading to reduction of B cells and short-lived plasma cells in the spleens. Use of ibrutinib may provide benefits to HLA-sensitized transplant patients for alloantibody suppression.     

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome*

ObjectivesTo assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients.MethodsIn this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected.ResultsA total of 253 patients (245 females) with confirmed pSS, aged 56.6 ± 13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio–OR– = 1.25 per OSS unit increase; confidence interval–CI–95% = 1.05–1.49; P = 0.01; OR = 1.31 per OSS unit increase; CI95% = 1.09–1.58, P = 0.002, and OR = 1.34 per OSS unit increase; CI95% = 1.12–1.59; P = 0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR = 2.03; CI95% = 1.03–4.00; P < 0.05 and OR = 2.52, CI95% = 1.31–4.90; P < 0.01, respectively).ConclusionAssociation between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.     

Association between the CX3CR1 gene V249I polymorphism and delayed kidney allograft function

BackgroundFractalkine is a member of the chemokine family that acts as an adhesion molecule and as an extracellular chemoattractant promoting cellular migration. In this study, we analysed the association between the CX3CR1 gene V249I (rs3732379) SNP and renal allograft function.MethodsThe study enrolled 270 Caucasian kidney allograft recipients. The following parameters were recorded in each case: the recipient's age and gender, delayed graft function (DGF) defined as the need for dialysis in the first 7 days after transplantation, occurrence and number of episodes of acute rejection (AR), and chronic allograft dysfunction (CAD).ResultsDelayed graft function was diagnosed in 39.2% of individuals with the CC genotype, 22.7% with CT and 23.5% of those with the TT genotype. The differences were statistically significant (CC vs. TT + CT: OR = 2.17; 95% CI = 1.28–3.70, p = 0.0042). In multivariate analysis the CC genotype was an independent and significant predictor of higher risk of DGF. The distribution of genotypes and alleles of the CX3CR1 gene polymorphism among patients with and without AR as well as CAD did not differ significantly.ConclusionsThe results of this study suggest that the CX3CR1 gene V249I (rs3732379) SNP CC genotype is associated with increased risk of DGF.