Spontaneous Remission in Paroxysmal Nocturnal Hemoglobinuria—Return to Health or Transition Into Malignancy?

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired syndrome characterized by intravascular hemolysis, thrombosis, and bone marrow failure. The disease is caused by a mutation in the PIG-A gene that leads to the lack of glycosylphosphatidylinositol-anchored complement regulatory molecules CD55 and CD59 on affected blood cell surfaces. In previous studies, spontaneous clinical remissions have been described. The disease manifestations are very heterogeneous, and we wanted to examine if true remissions and disappearance of the clone occur. In a follow-up of a nation-wide cohort of 106 Finnish patients with a PNH clone, we found six cases, where the clone disappeared or was clearly diminished. Two of the patients subsequently developed leukemia, while the other four are healthy and in clinical remission. According to our data, spontaneous remissions are not as frequent as described earlier. Since the disappearance of the PNH cell clone may indicate either a favorable or a poor outcome—remission or malignancy—careful clinical monitoring in PNH is mandatory. Nevertheless, true remissions occur, and further studies are needed to understand the immunological background of this phenomenon and to obtain a better understanding of the natural history of the disease

Saliva-based testing for diagnosis of SARS-CoV-2 infection : A meta-analysis

Non peer reviewe

Spontaneous Remission in Paroxysmal Nocturnal Hemoglobinuria-Return to Health or Transition Into Malignancy?

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired syndrome characterized by intravascular hemolysis, thrombosis, and bone marrow failure. The disease is caused by a mutation in the PIG-A gene that leads to the lack of glycosylphosphatidylinositol-anchored complement regulatory molecules CD55 and CD59 on affected blood cell surfaces. In previous studies, spontaneous clinical remissions have been described. The disease manifestations are very heterogeneous, and we wanted to examine if true remissions and disappearance of the clone occur. In a follow-up of a nation-wide cohort of 106 Finnish patients with a PNH clone, we found six cases, where the clone disappeared or was clearly diminished. Two of the patients subsequently developed leukemia, while the other four are healthy and in clinical remission. According to our data, spontaneous remissions are not as frequent as described earlier. Since the disappearance of the PNH cell clone may indicate either a favorable or a poor outcome-remission or malignancy-careful clinical monitoring in PNH is mandatory. Nevertheless, true remissions occur, and further studies are needed to understand the immunological background of this phenomenon and to obtain a better understanding of the natural history of the disease.Peer reviewe

Functional Recruitment of Human Complement Inhibitor C4b-Binding Protein to Outer Membrane Protein Rck of Salmonella

Peer reviewe

Fusobacterium necrophorum ja Lemierren oireyhtymä : Nuorten aikuisten septinen laskimotulehdus

English summaryPeer reviewe

Rapid increase in SARS-CoV-2 seroprevalence during the emergence of Omicron variant, Finland

Non peer reviewe

Genotypic and phenotypic diversity of Lactobacillus rhamnosus clinical isolates, their comparison with strain GG and their recognition by complement system

Lactobacillus rhamnosus strains are ubiquitous in fermented foods, and in the human body where they are commensals naturally present in the normal microbiota composition of gut, vagina and skin. However, in some cases, Lactobacillus spp. have been implicated in bacteremia. The aim of the study was to examine the genomic and immunological properties of 16 clinical blood isolates of L. rhamnosus and to compare them to the well- studied L. rhamnosus probiotic strain GG. Blood cultures from bacteremic patients were collected at the Helsinki University Hospital laboratory in 2005-2011 and L. rhamnosus strains were isolated and characterized by genomic sequencing. The capacity of the L. rhamnosus strains to activate serum complement was studied using immunological assays for complement factor C3a and the terminal pathway complement complex (TCC). Binding of complement regulators factor H and C4bp was also determined using radioligand assays. Furthermore, the isolated strains were evaluated for their ability to aggregate platelets and to form biofilms in vitro. Genomic comparison between the clinical L. rhamnosus strains showed them to be clearly different from L. rhamnosus GG and to cluster in two distinct lineages. All L. rhamnosus strains activated complement in serum and none of them bound complement regulators. Four out of 16 clinical blood isolates induced platelet aggregation and/or formed more biofilms than L. rhamnosus GG, which did not display platelet aggregation activity nor showed strong biofilm formation. These findings suggest that clinical L. rhamnosus isolates show considerable heterogeneity but are clearly different from L. rhamnosus GG at the genomic level. All L. rhamnosus strains are still normally recognized by the human complement system.Peer reviewe

Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p <0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (rho = 20.706; p <0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.Peer reviewe