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Background Kidney transplantation (KTx) is a strong trigger for the development of either recurrent or de novo atypical haemolytic uraemic syndrome (aHUS). According to previous studies, eculizumab (ECU) is effective for prophylaxis and for treatment of recurrence. Methods We evaluated the experiences of Spanish patients with recurrent and de novo aHUS associated with KTx, treated or not treated with ECU. In the de novo group, we classified patients as having early de novo (during the first month) or late de novo aHUS (subsequent onset). Results We analysed 36 cases of aHUS associated with KTx. All of the 14 patients with pre-KTx diagnosis of aHUS were considered to have high or moderate risk of recurrence. Despite receiving grafts from suboptimal donors, prophylactic ECU was effective for avoiding recurrence. The drug was stopped only in two cases with low–moderate risk of recurrence and was maintained in high-risk patients with no single relapse. There were 22 de novo aHUS cases and 16 belonged to the early de novo group. The median time of onset in the late group was 3.4 years. The early group had a better response to ECU than the late group, probably due to earlier diagnosis and use of the drug. No genetic pathogenic variant was detected in de novo aHUS cases, suggesting a secondary profile of the disease. ECU was stopped in all de novo patients with no relapses. ECU was well tolerated in all cases. Conclusions Both groups (pre-aHUS and de novo) presented different clinical profiles, management approaches and outcomes. One should consider aHUS regardless of time after KTx. Genetic studies are crucial to stratify risks of relapse and to determine necessary lengths of treatment. We suggest short ECU treatment for de novo cases without pathogenic mutation and that ECU treatment be considered pre-emptively for patients with moderate or high risk of recurrence. [ABSTRACT FROM AUTHOR]

Several mutations have been identified in the gene coding for Complement Factor H (FH) from patients with atypical Hemolytic Uraemic Syndrome (aHUS), Age-related Macular Degeneration (AMD) and Membranoproliferative Glomerulonephritis (MPGN). These data allow for a precise description of the structural changes affecting FH, but a simple test for specifically assessing FH function routinely is not yet of common use. We have produced and characterised a monoclonal antibody (5H5) which discriminates between FH and the smaller FH-like 1 and FH-related proteins and show here that it specifically binds to FH without detecting the smaller isoforms. We therefore used this mAb for a quick, one-step micro-purification of FH directly from control sera and showed that this affinity chromatography procedure is not disruptive of its cofactor function. We also developed a modified sheep erythrocytes haemolysis test using our antibody and affinity-purified FH. These tests can be used in conjunction for assessing the function of FH purified from patients affected by FH-related diseases. Moreover we used this mAb to develop a FH-specific ELISA test. [ABSTRACT FROM AUTHOR]

Autoantibody formation against Factor H (FH) is found in 7–10% of patients who are diagnosed with atypical haemolytic uraemic syndrome (aHUS). These autoantibodies predominately target the C-terminal cell binding recognition domain of FH and are associated with absence of FHR1. Additional autoantibodies have also been identified in association with aHUS, for example autoantibodies to Factor I. Based on this, and that there are genetic mutations in other complement regulators and activators associated with aHUS, we hypothesised that other complement regulator proteins, particularly surface bound regulators in the kidney, might be the target for autoantibody formation in aHUS. Therefore, we assayed serum derived from 89 patients in the Newcastle aHUS cohort for the presence of autoantibodies to CD46 (membrane cofactor protein, MCP), CD55 (decay accelerating factor, DAF), CD35 (complement receptor type 1, CR1; TP10) and CD59. We also assayed 100 healthy blood donors to establish the normal levels of reactivity towards these proteins in the general population. Recombinant proteins CD46 and CD55 (purified from Escherichia coli ) as well as soluble CR1 (CD35) and oligomeric C4BP-CD59 (purified from eukaryotic cell media) were used in ELISA to detect high responders. False positive results were established though Western blot and flow cytometric analysis. After excluding false positive responders to bacterial proteins in the CD46 and CD55 preparations, and responses to blood group antigens in CD35, we found no significant level of patient serum IgG reactivity with CD46, CD55, CD35 or CD59 above that detected in the normal population. These results suggest that membrane anchored complement regulators are not a target for autoantibody generation in aHUS. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation (KTx) is a strong trigger for the development of either recurrent or de novo atypical haemolytic uraemic syndrome (aHUS). According to previous studies, eculizumab (ECU) is effective for prophylaxis and for treatment of recurrence., Methods: We evaluated the experiences of Spanish patients with recurrent and de novo aHUS associated with KTx, treated or not treated with ECU. In the de novo group, we classified patients as having early de novo (during the first month) or late de novo aHUS (subsequent onset)., Results: We analysed 36 cases of aHUS associated with KTx. All of the 14 patients with pre-KTx diagnosis of aHUS were considered to have high or moderate risk of recurrence. Despite receiving grafts from suboptimal donors, prophylactic ECU was effective for avoiding recurrence. The drug was stopped only in two cases with low-moderate risk of recurrence and was maintained in high-risk patients with no single relapse. There were 22 de novo aHUS cases and 16 belonged to the early de novo group. The median time of onset in the late group was 3.4 years. The early group had a better response to ECU than the late group, probably due to earlier diagnosis and use of the drug. No genetic pathogenic variant was detected in de novo aHUS cases, suggesting a secondary profile of the disease. ECU was stopped in all de novo patients with no relapses. ECU was well tolerated in all cases., Conclusions: Both groups (pre-aHUS and de novo ) presented different clinical profiles, management approaches and outcomes. One should consider aHUS regardless of time after KTx. Genetic studies are crucial to stratify risks of relapse and to determine necessary lengths of treatment. We suggest short ECU treatment for de novo cases without pathogenic mutation and that ECU treatment be considered pre-emptively for patients with moderate or high risk of recurrence., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)