Anti-GBM disease in pregnancy.

We present the case of a pregnant woman in her 20s who presented in her second trimester with severe pulmonary haemorrhage and dialysis-dependent acute kidney failure due to antiglomerular basement membrane (GBM) disease. Responding to therapy, she recovered kidney function and delivered a baby. During her pregnancy, she developed cytomegalovirus viraemia, gestational diabetes and pre-eclampsia. Here, we report the first combined use of cyclophosphamide, rituximab and intensified plasma exchange in anti-GBM disease in pregnancy, allowing minimal exposure to cytotoxic medication, resulting in live birth and dialysis independence.

A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations.

Basement membranes (BMs) are ubiquitous extracellular matrices whose composition remains elusive, limiting our understanding of BM regulation and function. By developing a bioinformatic and in vivo discovery pipeline, we define a network of 222 human proteins and their animal orthologs localized to BMs. Network analysis and screening in C. elegans and zebrafish uncovered BM regulators, including ADAMTS, ROBO, and TGFß. More than 100 BM network genes associate with human phenotypes, and by screening 63,039 genomes from families with rare disorders, we found loss-of-function variants in LAMA5, MPZL2, and MATN2 and show that they regulate BM composition and function. This cross-disciplinary study establishes the immense complexity of BMs and their impact on in human health.

Genetic Disorders of the Glomerular Filtration Barrier.

The glomerular filtration barrier is a highly specialized capillary wall comprising fenestrated endothelial cells, podocytes, and an intervening basement membrane. In glomerular disease, this barrier loses functional integrity, allowing the passage of macromolecules and cells, and there are associated changes in both cell morphology and the extracellular matrix. Over the past 3 decades, there has been a transformation in our understanding about glomerular disease, fueled by genetic discovery, and this is leading to exciting advances in our knowledge about glomerular biology and pathophysiology. In current clinical practice, a genetic diagnosis already has important implications for management, ranging from estimating the risk of disease recurrence post-transplant to the life-changing advances in the treatment of atypical hemolytic uremic syndrome. Improving our understanding about the mechanistic basis of glomerular disease is required for more effective and personalized therapy options. In this review, we describe genotype and phenotype correlations for genetic disorders of the glomerular filtration barrier, with a particular emphasis on how these gene defects cluster by both their ontology and patterns of glomerular pathology.

Enzyme immunoassay of Cryptosporidium-specific immunoglobulin G antibodies to assess longitudinal infection trends in six communities in British Columbia, Canada.

A newly developed enzyme-linked immunosorbent assay (ELISA) that detects immunoglobulin G antibodies to the 27-kDa Cryptosporidium parvum sporozoite surface antigen was used to test 4,097 sera collected from pregnant women in 6 communities in British Columbia, Canada, between January 1996, and December 1997. Waterborne outbreaks of cryptosporidiosis occurred in two of the study communities during the period of follow-up, and ELISA seropositivity was high in all six communities during the study period (77% positive to 92% positive). In the community with the largest outbreak, levels of antibody to the 27-kDa antigen increased rapidly and then decayed to background levels within 3-4 months of the peak of the epidemic curve. Trends in serologic reactivity were complex in all communities, and increased antibody levels not related temporally to known waterborne outbreaks were also observed. Serological assays may provide more accurate information regarding community levels of Cryptosporidium infection.