Postvaccination anti-S IgG levels predict anti-SARS-CoV-2 neutralising activity over 24 weeks in patients with RA

OBJECTIVES To correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity. METHODS The RECOVER study was a prospective, monocentric study including patients with RA and healthy controls (HCs). Assessments were performed before, and 3, 6, 12 and 24 weeks, after the first vaccine dose, respectively, and included IgG, IgA and IgM responses (against receptor binding domain, S1, S2, N), IFN-γ ELISpots as well as neutralisation assays. RESULTS In patients with RA, IgG responses developed slower with lower peak titres compared with HC. Potent neutralising activity assessed by a SARS-CoV-2 pseudovirus neutralisation assay after 12 weeks was observed in all 21 HCs, and in 60.3% of 73 patients with RA. A significant correlation between peak anti-S IgG levels 2 weeks after the second vaccine dose and potent neutralising activity against SARS-CoV-2 was observed at weeks 12 and 24. The analysis of IgG, IgA and IgM isotype responses to different viral proteins demonstrated a delay in IgG but not in IgA and IgM responses. T cell responses were comparable in HC and patients with RA but declined earlier in patients with RA. CONCLUSION In patients with RA, vaccine-induced IgG antibody levels were diminished, while IgA and IgM responses persisted, indicating a delayed isotype switch. Anti-S IgG levels 2 weeks after the second vaccine dose correlate with the development of a potent neutralising activity after 12 and 24 weeks and may allow to identify patients who might benefit from additional vaccine doses or prophylactic regimen

Conserved stromal-immune cell circuits secure B cell homeostasis and function

B cell zone reticular cells (BRCs) form stable microenvironments that direct efficient humoral immunity with B cell priming and memory maintenance being orchestrated across lymphoid organs. However, a comprehensive understanding of systemic humoral immunity is hampered by the lack of knowledge of global BRC sustenance, function and major pathways controlling BRC-immune cell interactions. Here we dissected the BRC landscape and immune cell interactome in human and murine lymphoid organs. In addition to the major BRC subsets underpinning the follicle, including follicular dendritic cells, PI16$^{+}$ RCs were present across organs and species. As well as BRC-produced niche factors, immune cell-driven BRC differentiation and activation programs governed the convergence of shared BRC subsets, overwriting tissue-specific gene signatures. Our data reveal that a canonical set of immune cell-provided cues enforce bidirectional signaling programs that sustain functional BRC niches across lymphoid organs and species, thereby securing efficient humoral immunity

B-cell Zone Reticular Cell Microenvironments Shape CXCL13 Gradient Formation

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B-cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradient

Elucidating Disease Modifying Roles of Radio-resistant, CNS Resident Cells in a Rodent Model of Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that can manifest as relapsing-remitting MS or progressive MS. Autoreactive T cells play a dominant role in inducing disease. However the contribution of other cell types such as B cells or central nervous system (CNS) resident cells as disease modifiers is less clear, as are the factors that establish the local inflammatory microenvironment within the CNS. Two overarching themes studied in this thesis use a relapsing-remitting rodent model of MS to examine: 1) the disease modifying factors that contribute to exacerbated disease severity in the SJL/J mouse; 2) the cellular and molecular players that govern formation of brain meningeal infiltrates and their contribution to disease propagation. Here, using the mouse model of MS (Experimental Autoimmune Encephalomyelitis - EAE), I demonstrate that genetic disease modifiers in the radio-resistant CNS compartment contribute to exacerbated clinical EAE severity in the SJL/J mouse strain. Moreover, with respect to meningeal infiltration and disease progression, my studies reveal discrete mechanistic steps whereby CNS-infiltrating Th17 cells, interact with and remodel the meningeal stroma to induce chemotactic and survival factors that retain infiltrating immune cells. While lymphotoxin-beta receptor signaling, a pathway involved in organization of lymphoid-tissue architecture is not required for the structural remodeling of the stroma, secretion of B cell survival factors and consequent B cell accumulation are lymphotoxin-sensitive, as is the skewing of subsequent waves of T cell infiltration towards a pro-inflammatory Th17 phenotype. Taken together, these studies contribute towards our understanding of immunological and genetic disease modifiers as well as the mechanisms for meningeal follicle formation in the SJL/J EAE model of MS.Ph.D.2016-11-30 00:00:0

Protective fibroblastic niches in secondary lymphoid organs

Fibroblastic reticular cells (FRCs) are specialized fibroblasts of secondary lymphoid organs that provide the structural foundation of the tissue. Moreover, FRCs guide immune cells to dedicated microenvironmental niches where they provide lymphocytes and myeloid cells with homeostatic growth and differentiation factors. Inflammatory processes, including infection with pathogens, induce rapid morphological and functional adaptations that are critical for the priming and regulation of protective immune responses. However, adverse FRC reprogramming can promote immunopathological tissue damage during infection and autoimmune conditions and subvert antitumor immune responses. Here, we review recent findings on molecular pathways that regulate FRC-immune cell crosstalk in specialized niches during the generation of protective immune responses in the course of pathogen encounters. In addition, we discuss how FRCs integrate immune cell-derived signals to ensure protective immunity during infection and how therapies for inflammatory diseases and cancer can be developed through improved understanding of FRC-immune cell interactions.ISSN:0022-1007ISSN:1540-0069ISSN:1540-953

Evaluation of Polish citizens’ level of knowledge of potential side effects of cosmetics containing UV filters

INTRODUCTION: According to literature data, chemical sunscreens with UV filters can be one of the reasons for skin irritation and/or contact dermatitis as well as photoallergic eczema. An allergic reaction manifests itself in burning, itching, swelling, rash and blisters. The aim of study is to assess the knowledge of Polish citizens concerning the composition of sunscreen cosmetics and the effects of the photoprotection substances on the human body. MATERIAL AND METHODS: The survey was conducted on a representative group of Polish adults in February, 2016 (N = 125). An original questionnaire was used in this survey. Complex statistical analysis of the examined material was performed using Microsoft Excel 2010. RESULTS: It has been demonstrated that nearly 78.4% of people use sunscreen cosmetics, but only 52.8% of respondents pay attention to the composition of the purchased products. Less than 14% of respondents had knowledge of certain sunscreen photoprotection substances, such as oxybenzone. Up to 12.8% of respondents had experienced skin problems caused by cosmetics with UV filters. CONCLUSIONS: The conducted research, indicates the need for further education of Polish citizens concerning the composition of sunscreen cosmetics and the effects of the photoprotection substances on the human body.WSTĘP: Chemiczne filtry przeciwsłoneczne mogą być jedną z przyczyn podrażnienia i/lub zapalenia skóry oraz występowania fotoalergicznej egzemy. Reakcja alergiczna może przejawiać się pieczeniem, świądem, obrzękiem, wysypką i pęcherzami. Celem pracy jest ocena aktualnego poziomu wiedzy mieszkańców Polski z zakresu znajomości składu kosmetyków przeciwsłonecznych oraz wpływu substancji fotoprotekcyjnych na organizm człowieka. MATERIAŁ I METODY: Badanie zostało przeprowadzone w lutym 2016 r., na reprezentatywnej grupie dorosłych mieszkańców Polski (N = 125) z wykorzystaniem autorskiego kwestionariusza ankiety. Kompleksową analizę statystyczną badanego materiału wykonano za pomocą programu Microsoft Excel 2010. WYNIKI: Wykazano, że spośród zapytanych osób prawie 78,4% stosuje kosmetyki przeciwsłoneczne, jednakże na skład kupowanych produktów kosmetycznych zwraca uwagę jedynie 52,8% ankietowanych. Wiedzę na temat niektórych substancji fotoprotekcyjnych wchodzących w skład kosmetyków ochrony przeciwsłonecznej, np. oksybenzonu, ma niespełna 14% badanych. Problemów skórnych wywołanych kosmetykami z filtrem UV doświadczyło aż 12,8%. WNIOSKI: Przeprowadzone badania wskazują na konieczność dalszej edukacji mieszkańców Polski na temat składu kosmetyków przeciwsłonecznych oraz wpływu substancji fotoprotekcyjnych na organizm człowieka

Evaluation of Polish citizens’ level of knowledge of potential side effects of cosmetics containing UV filters

INTRODUCTION: According to literature data, chemical sunscreens with UV filters can be one of the reasons for skin irritation and/or contact dermatitis as well as photoallergic eczema. An allergic reaction manifests itself in burning, itching, swelling, rash and blisters. The aim of study is to assess the knowledge of Polish citizens concerning the composition of sunscreen cosmetics and the effects of the photoprotection substances on the human body. MATERIAL AND METHODS: The survey was conducted on a representative group of Polish adults in February, 2016 (N = 125). An original questionnaire was used in this survey. Complex statistical analysis of the examined material was performed using Microsoft Excel 2010. RESULTS: It has been demonstrated that nearly 78.4% of people use sunscreen cosmetics, but only 52.8% of respondents pay attention to the composition of the purchased products. Less than 14% of respondents had knowledge of certain sunscreen photoprotection substances, such as oxybenzone. Up to 12.8% of respondents had experienced skin problems caused by cosmetics with UV filters. CONCLUSIONS: The conducted research, indicates the need for further education of Polish citizens concerning the composition of sunscreen cosmetics and the effects of the photoprotection substances on the human body.WSTĘP: Chemiczne filtry przeciwsłoneczne mogą być jedną z przyczyn podrażnienia i/lub zapalenia skóry oraz występowania fotoalergicznej egzemy. Reakcja alergiczna może przejawiać się pieczeniem, świądem, obrzękiem, wysypką i pęcherzami. Celem pracy jest ocena aktualnego poziomu wiedzy mieszkańców Polski z zakresu znajomości składu kosmetyków przeciwsłonecznych oraz wpływu substancji fotoprotekcyjnych na organizm człowieka. MATERIAŁ I METODY: Badanie zostało przeprowadzone w lutym 2016 r., na reprezentatywnej grupie dorosłych mieszkańców Polski (N = 125) z wykorzystaniem autorskiego kwestionariusza ankiety. Kompleksową analizę statystyczną badanego materiału wykonano za pomocą programu Microsoft Excel 2010. WYNIKI: Wykazano, że spośród zapytanych osób prawie 78,4% stosuje kosmetyki przeciwsłoneczne, jednakże na skład kupowanych produktów kosmetycznych zwraca uwagę jedynie 52,8% ankietowanych. Wiedzę na temat niektórych substancji fotoprotekcyjnych wchodzących w skład kosmetyków ochrony przeciwsłonecznej, np. oksybenzonu, ma niespełna 14% badanych. Problemów skórnych wywołanych kosmetykami z filtrem UV doświadczyło aż 12,8%. WNIOSKI: Przeprowadzone badania wskazują na konieczność dalszej edukacji mieszkańców Polski na temat składu kosmetyków przeciwsłonecznych oraz wpływu substancji fotoprotekcyjnych na organizm człowieka

UV filters in cosmetics: Are they all safe for health?

Tanning benefits not only the skeletal and cardiovascular system, but also stimulates the immune system. On the other hand, sunlight impairs the human body, leading to sunburn, keratinization and a decrease in skin firmness. Moreover, tanning can result in skin cancer, which can be prevented not only by avoiding sources of UV radiation, but also by using sun cosmetics. Unfortunately, not all the ingredients used in their production guarantee safety. The article presents the potential influence of two popular UV filters used in cosmetic sunscreens – 2-hydroxy-4-methoxybenzophenone (oxybenzone, BP-3) and 2-ethylhexyl 4-methoxycinnamate (octyl methoxycinnamate, OMC), on health.Opalanie korzystnie wpływa na układ kostny, sercowo-naczyniowy oraz stymuluje układ odpornościowy. Z drugiej strony ekspozycja na promieniowanie słoneczne może mieć negatywny wpływ na organizm, powodując poparzenia, rogowacenie i zmniejszenie elastyczności skóry. Ponadto skutkiem opalania mogą być nowotwory skóry, którym zgodnie z obecnymi metodami profilaktyki można zapobiec przez unikanie źródeł promieniowania UV, a także stosowanie kosmetyków przeciwsłonecznych. Niestety nie wszystkie składniki używane do ich produkcji gwarantują nam bezpieczeństwo. W artykule przedstawiono potencjalny wpływ na zdrowie dwóch popularnych syntetycznych filtrów UV stosowanych w kosmetykach – 2-hydroksy-4-metoksybenzofenonu (benzophenone-3, benzofenon-3, BP-3, oksybenzon) oraz 4-metoksycynamonianu 2-etyloheksylu (octyl methoxycinnamate, oktylometoksycynamonian, OMC)

B Cells in the Multiple Sclerosis Central Nervous System: Trafficking and Contribution to CNS-Compartmentalized Inflammation

Clinical trial results of peripheral B cell depletion indicate abnormal proinflammatory B cell properties, and particularly antibody-independent functions, contribute to relapsing MS disease activity. However, potential roles of B cells in progressive forms of disease continue to be debated. Prior work indicates that presence of B cells is fostered within the inflamed MS central nervous system (CNS) environment, and that B cell-rich immune cell collections may be present within the meninges of patients. A potential association is reported between such meningeal immune cell collections and the subpial pattern of cortical injury that is now considered important in progressive disease. Elucidating the characteristics of B cells that populate the MS CNS, how they traffic into the CNS and how they may contribute to progressive forms of the disease has become of considerable interest. Here, we will review characteristics of human B cells identified within distinct CNS subcompartments of patients with MS, including the cerebrospinal fluid, parenchymal lesions, and meninges, as well as the relationship between B cell populations identified in these subcompartments and the periphery. We will further describe the different barriers of the CNS and the possible mechanisms of migration of B cells across these barriers. Finally, we will consider the range of human B cell responses (including potential for antibody production, cytokine secretion, and antigen presentation) that may contribute to propagating inflammation and injury cascades thought to underlie MS progression

Secondary B Cell Receptor Diversification Is Necessary for T Cell Mediated Neuro-Inflammation during Experimental Autoimmune Encephalomyelitis

<div><p>Background</p><p>Clinical studies of B cell depletion in Multiple Sclerosis (MS) have revealed that B Lymphocytes are involved in the neuro-inflammatory process, yet it remains unclear how B cells can exert pro- and anti-inflammatory functions during MS. Experimental Autoimmune Encephalomyelitis (EAE) is an animal model of MS whereby myelin-specific T cells become activated and subsequently migrate to the Central Nervous System (CNS) where they perform pro-inflammatory functions such as cytokine secretion. Typically EAE is induced by immunization of mice of a susceptible genetic background with peptide antigen emulsified in Complete Freund's Adjuvant. However, novel roles for B-lymphocytes in EAE may also be explored by immunization with full-length myelin oligodendrocyte glycoprotein (MOG) that contains the B cell conformational epitope. Here we show that full length MOG immunization promotes a chronic disease in mice that depends on antigen-driven secondary diversification of the B cell receptor.</p><p>Methods</p><p>Activation-Induced Deaminase (AID) is an enzyme that is essential for antigen-driven secondary diversification of the B cell receptor. We immunized AID^−/− mice with the extracellular domain (amino acids 1–120) of recombinant human MOG protein (rhMOG) and examined the incidence and severity of disease in AID^−/− versus wild type mice. Corresponding with these clinical measurements, we also evaluated parameters of T cell activation in the periphery and the CNS as well as the generation of anti-MOG antibodies (Ab).</p><p>Conclusions</p><p>AID^−/− mice exhibit reduced severity and incidence of EAE. This suggests that the secondary diversification of the B cell receptor is required for B cells to exert their full encephalogenic potential during rhMOG-induced EAE, and possibly also during MS.</p></div