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Introduction: Prognosis of lupus nephritis (LN) among patients of African descent living in Europe has been understudied., Methods: In a retrospective study performed in two European university hospitals, we compared the prognosis of LN in patients of African descent or Caucasians. Remission was defined as a urine protein to creatinine (uP/C) ratio<0.5 g/g and a serum creatinine value<120% of baseline. Renal relapse was defined as the reappearance of a uP/C>1 g/g, leading to a repeat kidney biopsy and/or immunosuppressive treatment change. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate≤60 mL/min/1.73 m 2 . Adherence was retrospectively assessed through medical files and/or hydroxychloroquine level measurements., Results: 52 patients of African descent and 85 Caucasian patients were included in this analysis. Class III and isolated class V LN were more common among patients of African descent. Time to first renal remission did not differ between ethnic subgroups. By contrast, patients of African descent suffered from earlier renal flares, CKD was more common and time to CKD was shorter after a flare. In a multivariate analysis, African ancestry was an independent risk factor for progression to CKD. We observed no significant difference in non-adherence to treatment between the two groups., Conclusion: LN patients of African descent have worse renal outcomes, mainly explained by a higher rate of renal flare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The very long-term consequences of absence of remission in lupus nephritis (LN) remain understudied., Methods: In this retrospective analysis, we studied a selected cohort of 128 patients with biopsy-proven class III, IV or V incident LN followed for a median period of 134 months (minimum 25). Remission was defined as a urine protein to creatinine (uP:C) ratio <0.5 g/g and a serum creatinine value <120% of baseline. Renal relapse was defined as the reappearance of a uP:C >1 g/g, leading to a repeat kidney biopsy and treatment change. Poor long-term renal outcome was defined as the presence of chronic kidney disease (CKD)., Results: Twenty per cent of patients never achieved renal remission. Their baseline characteristics did not differ from those who did. Absence of renal remission was associated with a threefold higher risk of CKD (48% vs 16%) and a 10-fold higher risk of end-stage renal disease (20% vs 2%). Patients achieving early remission had significantly higher estimated glomerular filtration rate (eGFR) at last follow-up compared with late remitters. Accordingly, patients with CKD at last follow-up had statistically longer time to remission. Among patients who achieved remission, 32% relapsed, with a negative impact on renal outcome, that is, lower eGFR values and higher proportion of CKD (33% vs 8%)., Conclusion: Early remission should be achieved to better preserve long-term renal function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) organisms are groups of pathogenic strains whose infections are characterized by a typical lesion of enterocyte attachment and effacement. They are involved in enteric diseases both in humans and in animals, and EHEC strains can be responsible for hemolytic uremic syndrome in humans. Previously, it was shown that the 2F3 monoclonal antibody (MAb) is specific for the O26 EHEC and EPEC strains (P. Kerr, H. Ball, B. China, J. Mainil, D. Finlay, D. Pollock, I. Wilson, and D. Mackie, Clin. Diagn. Lab. Immunol. 6:610-614, 1999). As these groups of bacteria play an important role in pathology, the aim of this paper was to characterize the antigen recognized by the 2F3 MAb and its genetic determinant. A genomic locus containing the entire O-antigen gene cluster and half of the colanic acid gene cluster from an O26 EHEC strain was shown to be sufficient for the production of the antigen recognized by the 2F3 MAb in an E. coli DH5alpha strain. By transposon mutagenesis performed on the recombinant plasmid, all 2F3 enzyme-linked immunosorbent assay-negative mutants had their transposons inserted into the O-antigen gene cluster. The O-antigen gene cluster was also cloned from an O26 EHEC strain into the E. coli DH5alpha strain, which then produced a positive result with the 2F3 MAb. Further analysis of the type of lipopolysaccharides (smooth or rough) produced by the clones and mutants and of the O antigen of the 2F3-positive clones confirmed that the epitope recognized by the 2F3 MAb is located on the O antigen in the O26 EHEC and EPEC strains and that its genetic determinant is located inside the O-antigen gene cluster.

Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) infections are characterised by the formation of attaching and effacing lesions on intestinal epithelial cells. The first step of EPEC and EHEC pathogenesis involves the initial adherence of the bacterium to the intestinal epithelium. A collection of bovine EPEC and EHEC strains belonging to different serogroups was tested by colony blot hybridization with gene probes for putative adhesins (BFPA, LPFA, IHA, LIFA) of human EPEC and EHEC, and also for fimbrial and afimbrial adhesins (AFA8, F17, Cs31A) of bovine necrotoxigenic E. coli (NTEC). In the bovine EPEC and EHEC strains tested, sequences homologous to lifA, ihA, and lpfA genes were detected, sometimes in association with particular serogroups. Bovine 026 EPEC also possessed a sequence homologous to a gene of the c/p operon, coding for the CS31A adhesin, associated with bovine NTEC. Overall results showed that different genes encoding for putative adhesins of human EHEC strains are present in bovine EPEC and EHEC strains, but not one of them is present in all strains.

Non-enterotoxigenic type A Clostridium perfringens are associated with bovine enterotoxaemia, but the alpha toxin is not regarded as responsible for the production of typical lesions of necrotic and haemorrhagic enteritis. The purpose of this study was to investigate the putative role of the more recently described beta2 toxin. Seven hundred and fourteen non-enterotoxigenic type A C. perfringens isolated from 133 calves with lesions of enterotoxaemia and high clostridial cell counts (study population) and 386 isolated from a control population of 87 calves were tested by a colony hybridisation assay for the beta2 toxin. Two hundred and eighteen (31%) C. perfringens isolated from 83 calves (62%) of the study population and 113 (29%) C. perfringens isolated from 51 calves (59%) of the control population tested positive with the beta2 probe. Pure and mixed cultures of four C. perfringens (one alpha+beta2+, one alpha+enterotoxin+ and two alpha+) were tested in the ligated loop assay in one calf. Macroscopic haemorrhages of the intestinal wall, necrosis and haemorrhages of the intestinal content, and microscopic lesions of necrosis and polymorphonuclear and mononuclear cell infiltration of the intestinal villi were more pronounced in loops inoculated with the alpha and beta2-toxigenic C. perfringens isolate. These results suggest in vivo synergistic role of the alpha and beta2 toxins in the production of necrotic and haemorrhagic lesions of the small intestine in cases of bovine enterotoxaemia. However, isolation of beta2-toxigenic C. perfringens does not confirm the clinical diagnosis of bovine enterotoxaemia and a clostridial cell counts must still be performed.

Attaching and effacing Escherichia coli (AEEC) virulence genes include the eae, the tir, the espA and the espB genes. These genes have been sequenced from several AEEC strains. The sequences alignments revealed the presence of constant and variable regions. Multiplex polymerase chain reactions were developed, in order to determine the subtype of each gene present in a particular isolate. AEEC strains isolated from calves dead of diarrhea, from healthy calves and from infected humans were compared. The same pathotypes were found in sick and healthy calves but in inverted proportion. These pathotypes were also found in human AEEC. Although, the human EHEC strains from serotype O157 possessed their own pathotype.

Enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) Escherichia coli isolated from cattle were studied by DNA colony hybridization to subtype their intimin-encoding (eae) gene with probes derived from the variable parts of the eae alpha gene of the human EPEC strain E2348/69, the eae gamma gene of the human O157:H7 EHEC strain ATCC43888, and the eae beta gene of the bovine O26:H- EHEC strain 193, whose eae gene was first cloned and sequenced during this work. The EPEC and EHEC had been isolated from diarrhoeic calves (143 EPEC and 48 EHEC) and from healthy animals at the slaughterhouse (10 EPEC and 34 EHEC). The 191 bovine EPEC and EHEC isolated from diseased calves were positive with the Eae beta probe (55 and 27% respectively) and with the Eae gamma probe (9 and 73% respectively), whereas 52 EPEC (36%) were negative with the Eae alpha, Eae beta, and Eae gamma probes. The results were different for the 44 bovine EPEC and EHEC isolated from healthy cattle at slaughterhouses: most tested positive with the Eae gamma probe (80 and 82% respectively) and the remaining (20 and 18% respectively) with the Eae beta probe. Nine O26 human EHEC tested positive with the Eae beta probe and seven O111 with the Eae gamma probe. The bovine and human EPEC and EHEC belonging to these two serogroups gave identical results: the 18 bovine and human O26 isolates tested positive with the Eae beta probe, whereas the 13 O111 isolates were positive with the Eae gamma probe. In contrast, the isolates belonging to other serogroups (O5, O15, O18, O20, and O118) gave more variable results. The eae beta and eae gamma, but not the eae alpha, variants were thus distributed amongst bovine EPEC and EHEC. The eae beta variant seemed to be more frequently associated with the presence of clinical signs in calves, but one third of EPEC from diarrhoeic calves carried an eae gene variant other than the alpha, beta, or gamma variants. In addition, the use of these gene probes did not enable differentiation between bovine and human EHEC belonging to the same O serogroup.

Enteropathogenic Escherichia coli (EPEC) produce attaching and effacing lesions. The genes responsible for this lesion are clustered on the chromosome forming a 35.5 kilobase pathogenesis island called LEE. The LEE was identified, characterized and completely sequenced from the human EPEC strain E2348/69. The LEE carries genes coding for: a type III secretion system (genes esc and sep), the translocated intimin receptor (gene tir), the outer membrane protein intimin (gene eae) and the E. coli secreted proteins EspA, EspB, and EspD (genes esp). In addition to man and farm animals, EPEC are also isolated from dogs and cats. We studied structurally and functionally the LEE of dog and cat EPEC. First, we used four probes scattered along the LEE to identify the presence of a LEE in canine and feline EPEC isolates. Second, by PCR, we checked the presence of genes homologous to eae, sep, esp, and tir genes in these strains. Third, since the four types of eae and tir genes were described, we developed a multiplex PCR in order to determine the type of eae and tir genes present in each strain. Fourth, we determined by PCR the site of the LEE insertion on the chromosome. Fifth, we tested several of the canine EPEC in their capacity to induce attaching and effacing lesions in the rabbit intestinal loop assay. We can conclude from this study: first, that the a LEE-like structure is present in all tested strains and that it contains genes homologous to esp, sep, tir, and eae genes; second, that there is some preferential associations between the type of eae gene and the type of tir gene present in a strain; third, that the majority of the tested strains contained a LEE located elsewhere on the chromosome in comparison to the human EPEC strain E2348/69; and fourth that dog EPEC were able to induce attaching and effacing lesions in rabbit ileal loop assay.

Attaching and effacing Escherichia coli (AEEC) has been described as a cause of diarrhea in calves. The molecular pathogenesis of AEEC was mainly studied in human enteropathogenic E. coli strain E2348/69 in which the virulence correlated with the presence of a 35.4 kb pathogenesis island called LEE. We showed that several strains isolated from calves with diarrhea were able to produce attaching and effacing lesions in a rabbit ileal loop model and that they possess a pathogenesis island related to the LEE. Moreover, we showed that the LEE from bovine strains was inserted mainly at a different position in the chromosome compared to the human enteropathogenic E. coli strain E2348/69.