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Common respiratory viral infections (CRVIs) frequently complicate hematopoietic stem cell transplantation (HSCT). We conducted a retrospective, single-center, observational cohort study to determine the incidence of CRVI in patients who received an allogeneic (allo) or autologous (auto) HSCT at the Royal Adelaide Hospital between 2009 and 2017. The median follow-up was 8.9 and 4.5 years for auto- and allo-HSCT recipients, respectively. There were 149 CRVI episodes in 74 patients, with rhinovirus being the most commonly isolated virus (n = 81, 47%). The majority of CRVIs (113/149, 75.8%) occurred more than 100 days post-HSCT and 67% were diagnosed in the outpatient setting. There was evidence of lower respiratory tract infection (LRTI) in 45.6% (68/149) of CRVIs. On multivariate logistic regression analysis, coviral infections and cytomegalovirus viremia were independent risk factors for progression of CRVI to LRTI. Ten (6.7%) CRVI episodes resulted in admission to intensive care for ventilatory support and 8 (5.4%) patients died within 30 days of CRVI diagnosis. In our study, 10.4% of HSCT recipients experienced a CRVI post-transplant, primarily causing late morbidity and potentially mortality. Prevention with strict infection control practices, vaccination, and patient education is essential.

The pathogenesis of transplant glomerulopathy (TG) remains unclear, with evidence of human leukocyte antigen (HLA) antibodies as important contributors to the disease. We studied the risk factors and the associations of HLA antibodies in the development of TG. Sixty-one cases with morphologic features of TG were identified and compared with contemporaneous matched patients (without TG) from a 17-year period, all undergoing renal biopsy in a single center. Univariate risk factors for TG were previous glomerulitis [odds ratio (OR) 3.3, 95% confidence interval (95% CI) [1.2-9.4], p = 0.025), delayed graft function (OR 2.3 [1.0-5.1], p = 0.042), HLA class I presensitization defined by Luminex solid-phase immunoassays (OR 5.0 [2.3-11.0]. p0.001), and de novo posttransplant development of donor HLA specific antibody (DSA) (OR 4.7 [1.7-13.2], p = 0.002). Only DSA remained significantly associated with TG after adjustment (OR 3.8 [1.1-12.9], p = 0.032). DSA was detected in50% of TG patients, suggesting HLA antibodies play a critical role in TG pathogenesis. TG patients with DSA had increased risk of graft loss (median graft survival 4.4-5.2 years), whereas patients with morphologic features of TG without DSA had similar graft survival compared with the non-TG group (median graft survival 15 years). Thus, DSA is a useful predictor for graft failure in TG patients.

B-cell crossmatch (BXM) was originally introduced to increase the sensitivity to detect anti-HLA antibodies of conventional CDC crossmatch in renal transplantation. Newer techniques such as Luminex((R)) have greater sensitivity in detecting anti-HLA antibodies but have not been directly evaluated versus BXM. We discuss our experience with Luminex testing and the significance of donor-specific antibodies (DSA) defined by Luminex in three populations, as compared with the CDC crossmatch. In the general transplant population, Luminex-defined DSA were found in only one third of positive CDC-BXM and were associated with graft rejection. Luminex testing enhanced the interpretation of CDC-BXM and identified patients with clinically relevant BXM. In the highly sensitized transplant population, Luminex-defined DSA were found in two thirds of positive BXM and were a better predictor of graft rejection. Therefore, Luminex assays rather than CDC-BXM should be used to facilitate kidney allocation in highly sensitized patients. In the post-transplantation population, Luminex antibody monitoring for DSA was shown to be important, as it defined low-level de novo DSA that were associated with development of transplant glomerulopathy and a significant predictor of graft loss in those patients. Thus Luminex testing facilitated the interpretation of CDC-BXM and provided a useful predictive tool for the detection of clinically significant DSA in post-transplantation antibody monitoring.

The common marmoset (Callithrix jacchus) is emerging as a promising alternative pre-clinical model for transplantation and immunological research. It is therefore important to establish a rapid and reliable method of confirming alloreactivity between donor-recipient pairs. In this study of a large marmoset colony (n=49), we firstly characterised MHC Class II genes (Caja-DRB*W1201, Caja-DRB1*03, Caja-DRB*W16) using, for the first time in this species, sequence-based allelic typing techniques. Exon 2 was amplified using M13-tailed PCR primers specific for known marmoset alleles, and sequenced using universal M13 sequencing primers and dye terminator cycle sequencing. Twenty-six genotypes involving monomorphic Caja-DRB*W1201, 8 Caja-DRB*W16 and 5 Caja-DRB1*03 alleles were observed. Two new DRB*W16 alleles were identified. Subsequently we investigated whether matching at MHC-DRB loci alone could accurately predict in-vitro alloreactivity as assessed by mixed lymphocyte reactions. Peripheral blood mononuclear cells (PBMC) isolated from fully and partially DRB-matched and fully mismatched animal pairs were mixed and co-cultured for T-cell proliferation. PBMC co-cultured from fully or partially mismatched pairs exhibited significant T cell proliferation above single cell controls (p0.01). Mixed PBMC from fully DRB-matched pairs exhibited no proliferation over controls (p=0.3). Thus using Caja-DRB genotyping, suitably alloreactive donor-recipient pairs can be rapidly and accurately identified for use in further studies of cellular and solid organ transplantation.

The purpose of this study was to examine the relationship between preterm birth and 22 single nucleotide polymorphisms in genes that encode cytokines and mediators of apoptosis and host defense.Two hundred two white women with a spontaneous preterm birth of35 weeks of gestation were compared with 185 white women with term births. Genotyping was performed with polymerase chain reaction and sequence specific primers. Multivariable analyses included demographic and genetic variables.Alcohol (multivariable odds ratio, 2.3; P = .001] and substance use (multivariable odds ratio, 3.7; P = .01) were associated with preterm birth at35 weeks of gestation. Smoking (multivariable odds ratio, 2.3; P = .03), haplotypes IL10 -1082A/-819T/-592A (multivariable odds ratio, 2.1; P = .04), tumor necrosis factor ( TNF )+488A/-238G/-308G (multivariable odds ratio, 2.4; P = .04), and IL4 -509C/C (multivariable odds ratio, 3.4; P = .02), and the presence of MBL2 codon 54Asp (multivariable odds ratio, 2.3; P = .02) were associated independently with preterm birth at29 weeks of gestation. Homozygosity for IL10 -1082G/-819C/-592C haplotype (multivariable odds ratio, 1.9; P = .02) was more common in women with preterm premature rupture of membranes.Polymorphisms in immunoregulatory genes may influence susceptibility to preterm birth or premature rupture of membranes.