Factor H is a pivotal complement regulatory protein that is preferentially produced by the liver and circulates in high concentrations in serum. There has been an increasing interest in the... Show moreFactor H is a pivotal complement regulatory protein that is preferentially produced by the liver and circulates in high concentrations in serum. There has been an increasing interest in the extrahepatic production of comple-ment factors, including by cells of the immune system, since this contributes to non-canonical functions of local complement activation and regulation. Here we investigated the production and regulation of factor H and its splice variant factor H-like protein 1 (FHL-1) by human myeloid cells. As validation, we confirmed the pre -dominant presence of intact factor H in serum, despite a strong but comparable mRNA expression of CFH and FHL1 in liver. Comparable levels of CFH and FHL1 were also observed in renal tissue, although a dominant staining for FHL-1 was shown within the proximal tubules. Human in vitro generated pro-and anti-inflammatory macrophages both expressed and produced factor H/FHL-1, but this was strongest in pro-inflammatory macro-phages. Production was not affected by LPS activation, but was increased upon stimulation with IFN-gamma or CD40L. Importantly, in both macrophage subsets mRNA expression of FHL1 was significantly higher than CFH. More -over, production of FHL-1 protein could be confirmed using precipitation and immunoblotting of culture su-pernatants. These data identify macrophages as producers of factor H and FHL-1, thereby potentially contributing to local complement regulation at sites of inflammation. Show less
Matern, B.M.; Niemann, M.; Nemparis, I.; Schimanski, A.; Peereboom, E.T.M.; Kramer, C.S.M.; ... ; Spierings, E. 2023
The International HLA and Immunogenetics Workshop (IHIW) is a recurring gathering of researchers, technologists and clinicians where participants contribute to collaborative projects with a variety... Show moreThe International HLA and Immunogenetics Workshop (IHIW) is a recurring gathering of researchers, technologists and clinicians where participants contribute to collaborative projects with a variety of goals, and come to consensus on definitions and standards for representing HLA and immunogenic determinants. The collaborative and international nature of these workshops, combined with the multifaceted goals of several specific workshop components, necessitates the collection and curation of a wide assortment of data, as well as an adaptable platform for export and analysis. With the aim of ensuring data quality and creation of reusable datasets, specific standards and nomenclature conventions are continuously being developed, and are an integral part of IHIW. Here we present the 18th IHIW Database, a purpose-built and extensible cloud-based file repository and web application for collecting and analyzing project-specific data. This platform is based on open-source software and uses established HLA data standards and web technologies to facilitate de-centralized data repository ownership, reduce duplicated efforts, and promote continuity for future IHIWs. Show less
Peereboom, E.T.M.; Matern, B.M.; Tomosugi, T.; Niemann, M.; Drylewicz, J.; Joosten, I.; ... ; Spierings, E. 2021
CD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft.... Show moreCD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4(+) memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4(+) memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4(+) memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4(+) memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation. Show less
