Rozprawy doktorskie na temat „Tetanus – Vaccination”

Vaccination coverage in adults remains suboptimal. Health organisations have only recently begun to recognise the role of socio-psychological factors in vaccination decisions. These factors are particularly important, given that they are inherently amenable to policy and behaviour change. This thesis employs a mixed-methods approach to investigate the determinants of adult seasonal influenza and tetanus vaccination in the UK general adult population. It focuses on socio-psychological factors and draws upon health behaviour models, heuristics and biases and customer journey mapping theoretical approaches to guide research and elucidate findings. A narrative and a systematic review and meta-analysis reveal there are a number of socio-psychological factors frequently associated with vaccination, particularly influenza and influenza vaccine risk perception, perceived vaccine effectiveness and reported physician recommendation, and show that most of the evidence in this area is produced in the US. They also highlight the importance of some vaccine risk perceptions, such as influenza-like symptoms and unspecific side-effects, and demonstrate that the existing evidence is highly heterogeneous and often lacking in quality, further supporting a case for robust empirical research on this topic. Two qualitative studies show that vaccine uptake is largely driven by people’s risk perception of influenza and tetanus, and that the tetanus vaccine is perceived as safe, unlike the influenza vaccine. They also reveal how specific healthcare ‘touchpoints’ across the immunisation journey can facilitate or hinder uptake. A novel finding is that certain childhood experiences can influence adult vaccination decisions. Two cross-sectional survey studies show that a compact set of variables can predict 91% of influenza and 75% of tetanus vaccination behaviour. They also demonstrate that socio-psychological factors are the most important determinants of vaccination behaviour. This thesis shows that incorporating socio-psychological dimensions in all aspect of immunisation policy, from surveillance systems to policy evaluation, is critical to improve vaccination rates.

Class of 2014 Abstract
Specific Aims: Tetanus, diphtheria, and pertussis are diseases, which are preventable through proper vaccination. In spite of the availability these vaccines, however, there has recently been a surge in the number of pertussis cases in the United States. The objective of this study is to determine provider adherence to tetanus, diphtheria and pertussis guidelines set forth by the Advisory Committee on Immunization Practices in a primary care setting before and after a clinical pharmacist intervention. Methods: A retrospective cohort of chart reviews was conducted between January 1 – September 30, 2013 to determine immunization adherence to tetanus, diphteria, and pertussis vaccination guidelines. A clinical pharmacist then preformed a series of cross-sectional chart reviews as an intervention. Following the intervention, a retrospective chart review was conducted to evaluate if Tdap vaccination rates improved between March 17-23, 2014. Main Results: Overall immunization rates greatly improved following the intervention (p<0.0001; x2=44.988). For non-pregnant adults between the ages of 19-64 the vaccination rate improved from 26% to 61.1% (p<0.0001; x2=47.07). A statistically significant improvement was not seen in the groups with patients 65 or older or pregnant women (p>0.05). Tdap vaccination status was appropriately evaluated and vaccinations given by primary doctors improved from 17.7% to 61.2% and those prescribed by nurse practitioners improved from 22.4% to 56.3%. Conclusion: Intervention by a Clinical Pharmacist helped improve overall provider adherence to the tetanus, diphteria, and pertussis vaccination guidelines.

Vaccination is one of the most efficacious public health interventions1 and has been increasingly used to combat non-infectious diseases. Mechanisms underlying vaccine responses overlap with those regulating immune responses in health and disease. Therefore, an understanding of mechanisms underpinning these responses will have broad implications. Variation in immune response genes contributes to impaired vaccine responses2-4. Understanding the contribution of genetic variants to vaccine responses is likely to be particularly important in early life given the generalized functional immaturity of the immune system in infants and the highly variable kinetics of its maturation over the first few years of life5-7. However, studies of genetic influences on early childhood vaccine responses are scarce. Since a number of genes from several pathways are likely to be important, a targeted approach is necessary. This thesis explored the effects and interactions of genes associated with atopy, as atopy, or the genetic risk for it, has been associated with modulation of early childhood vaccine responses. This thesis aimed to: 1) investigate genetic variants associated with atopy on early childhood vaccine responses; 2) examine interactions between these genetic variants and non-genetic factors; 3) approach developmental genetic influences on genetic effects and their interactions; and 4) extend findings on vaccine responses to other immunological phenotypes and disease outcomes.

JESSICA MASTRODOMENICO An Examination of the Socio-Demographic Characteristics Associated with Adult Vaccination Prevalence for Preventable Diseases in the United States Background: An estimated 50,000 adults in the United States (U.S.) die each year from one of 10 vaccine preventable diseases. For those who survive vaccine preventable infections, health care costs and loss of income become more significant. While children in the U.S. aged 0-2 exhibit vaccine prevalence rates of almost 90%, some adult vaccine prevalence rates in the U.S. population are reported to be nearly 30-40% less than the goals set forth by Healthy People 2010. The purpose of this study was to examine the associations between socio-demographic characteristics of U.S. adults and adult vaccination prevalence for pneumococcal, hepatitis A, hepatitis B, tetanus, and pertussis. Methods: Data from the 2008 National Health Interview Survey were assessed examining various health indicators and characteristics of non-institutionalized adults and children. The sample was restricted to adults ≥18 years of age. Odds ratios were calculated and multivariate logistic regression was also conducted. P-values of <0.05 and 95% confidence intervals were used to determine statistical significance. Results: There were 21781 total observations; 19.3% received the pneumococcal vaccine, 9.4% received the hepatitis A vaccine, 27.2% received the hepatitis B vaccine, 55.1% received the tetanus vaccine, and 15.2% received the pertussis vaccine. Of the socio-demographic characteristics examined, age, health insurance, marital status, and education were significant for either all five or at least four of the vaccines included in this study. As one might expect those who reported health insurance and those who had a higher level of education usually had a higher likelihood of vaccine receipt as compared to those without health insurance and those with less than a high school education. Age associations varied due to age-related recommendations for certain vaccines such as pneumococcal (recommended for adults ≥65). Compared to the married population (referent), marital status results varied, but for reasons unclear. Whites, the referent group, were the most likely to be vaccinated as compared to Blacks, Hispanics/Latinos, and Asians. Hispanics/Latinos typically had the lowest likelihood of vaccination in this examination. Conclusions: This study further explores the impact of socio-demographic disparities on vaccination status and adds new information to the literature regarding adult vaccination rates for preventable diseases. While research exists related to strengthening interventions such as patient reminder systems, those who do not see the same health care providers on a regular basis remain at risk for lower vaccination prevalence. It is important to better understand the role of social determinants of health, specifically in terms of vaccinations. Future research is needed to further characterize the association of socio-demographic factors with receipt of optional vaccines in adults.

A cross-sectional study was conducted based on the secondary analysis of the Demographic and Family Health Survey (ENDES) 2019, with the objective of estimating the incomplete coverage of PTD and determining the factors associated with it in infants aged 12 to 23 months in Peru. Pearson's chi-square test was used for the bivariate analysis and the magnitude of the association was estimated using the crude (PRc) and adjusted (RPa) prevalence ratios. Incomplete DPT coverage was 12.4% (CI 11.88-14.79) for the entire population studied. Infants in the third order of birth or more (PRa: 1.37; CI 1.01-1.84) and infants born by non-institutionalized delivery were more likely than children whose delivery was institutionalized (PRa; 1.70; CI 1.15-2.54). The probability of having incomplete coverage decreased by having 6 or more prenatal check-ups (PRa; 0.58; CI 0.46-0.73), as well as living in rural areas compared to living in urban areas (PRa; 0.64; CI 0.48-0.85). Incomplete DPT vaccination in infants aged 12 to 23 months in Peru has a high level (> 10%), placing this population group at risk of suffering from these immunopreventable diseases and triggering outbreaks and epidemics in the community. The factors associated with incomplete vaccination are related to lower socioeconomic conditions and limited access to health services, which is why it is necessary to focus the interventions of the National Immunization Health Strategy to reverse this situation.
Se realizó un estudio transversal basado en el análisis secundario de la Encuesta Demográfica y de Salud Familiar (ENDES) 2019, con el objetivo de estimar la cobertura incompleta de DPT y determinar los factores asociados a la misma en infantes de 12 a 23 meses en el Perú. Se utilizó la prueba chi cuadrado de Pearson para el análisis bivariado y la magnitud de la asociación se estimó mediante las razones de prevalencia crudas (RPc) y ajustadas (RPa). La cobertura incompleta de DPT fue de 12.4% (IC 11.88-14.79) para toda la población estudiada. Mayores probabilidades de cobertura incompleta tuvieron los infantes en tercer orden de nacimiento o más (PRa: 1.37; IC 1.01-1.84) y los infantes nacidos por parto no institucionalizado con respecto a los infantes cuyo parto fue institucionalizado (PRa; 1,70; IC 1.15-2.54). Disminuyó la probabilidad de tener cobertura incompleta el contar con 6 o más controles prenatales (PRa; 0.58; IC 0.46-0.73), así como vivir en el área rural con respecto a vivir en el área urbana (PRa; 0.64; IC 0.48-0.85). La vacunación incompleta de DPT en infantes de 12 a 23 meses en el Perú tuvo un nivel alto (>10%), colocando a este grupo poblacional en riesgo de padecer estas enfermedades inmunoprevenibles y desencadenar brotes y epidemias en la comunidad. Los factores asociados a la vacunación incompleta estuvieron relacionados a menores condiciones socioeconómicas y al acceso limitado a servicios de salud por lo que es necesario focalizar las intervenciones de la Estrategia Sanitaria Nacional de Inmunizaciones para revertir esta situación.
Tesis

Trata-se de uma pesquisa com o objetivo de compreender o adoecimento pelo tétano neonatal, a partir da análise da trajetória de um grupo de 19 mães de crianças que morreram em conseqüência da doença no período compreendido entre 1997 e 2002, em municípios do Estado de Minas Gerais, Brasil. Para a análise, foram utilizadas Políticas de Assistência à Saúde da Mulher, Imunização e a Estratégia de Saúde da Família. Os dados foram obtidos em entrevistas semi-estruturadas e nos registros secundários do Cartão de Vacina e do Cartão da Gestante. A metodologia adotada foi de natureza quantitativa e qualitativa, com enfoque nas representações sociais sobre a experiência da doença e o risco de adoecimento. Para a análise das entrevistas, utilizou-se o instrumento do discurso do sujeito coletivo. As mulheres, em sua maioria, são multíparas em idade fértil, desconhecem a doença e seus mecanismos de prevenção, embora relatem as principais manifestações clínicas do tétano neonatal associando-o ao mal-de-sete-dias. São evidentes as práticas de tratamento inadequado do coto umbilical utilizadas pelas mulheres, sedimentadas no risco potencial para a doença, a irregularidade do pré-natal, a ausência ou a administração de doses insuficientes de vacina para a proteção do tétano neonatal e do tétano acidental, e procedimentos pós-parto domiciliar impróprios utilizados pelas parteiras ou curiosas. Observou-se, pelas falas das mães, a presença da crendice sobre os cuidados com o coto umbilical e a falha dos serviços no processo de educação para a saúde. Urge implementar esforços estratégicos específicos, direcionados à vigilância epidemiológica, à capacitação de parteiras e aos profissionais de saúde, incrementar serviços de pré-natal e ampliar a cobertura vacinal para as mulheres, principalmente nas regiões de onde provêm os casos da pesquisa, contribuindo, assim, para a eliminação da doença.
This research aimed to understand the illness caused by neonatal tetanus, based on the analysis of a group of 19 mothers’ histories involving children who died of the disease in communities located in the State of Minas Gerais, Brazil, between 1997 and 2002. The analysis was based on Women’s Health Care and Immunization Policies and the Family Health Strategy. Data were collected through semistructured interviews and secondary records from the Vaccination Card and the Pregnant Woman’s Card. A quantitative and qualitative methodology was adopted, focusing on the social representations about the disease experience and the risk of getting ill. The interviews were analyzed on the basis of collective subject discourse. Most women were of fertile age and multiparous and did not know about the disease and its prevention mechanisms, although they reported on the main clinical signs of neonatal tetanus, associating it with the “seven-day disease”. This study revealed the women’s use of inadequate practices for treating the umbilical cord stump, based on the potential risk of catching the disease, irregular antenatal treatment, the absence or administration of insufficient doses of the vaccine to protect against neonatal and accidental tetanus, and inappropriate post-home delivery procedures used by midwifes. The mothers’ discourse revealed the presence of popular beliefs on care related to the umbilical cord stump and the services’ deficiency in the health education process. There is an urgent need to implement specific strategic efforts, aimed at epidemiological supervision, the training of midwifes and health professionals, and to increase prenatal services and expand vaccination coverage for women, mainly in the research cases’ regions of origin, thus contributing to the elimination of this disease.

Introdução: A vacina tríplice acelular de adultos (dTpa) foi introduzida no Programa Nacional de Imunizações (PNI) em novembro de 2014, sendo recomendada para gestantes e profissionais de saúde (PS) que têm contato com gestantes e recém-nascidos. De abril a dezembro de 2015, foram implementadas várias estratégias para aumentar a cobertura vacinal entre os profissionais do Instituto Central do Hospital das Clínicas da FMUSP. Objetivos: Avaliar a cobertura vacinal entre os PS após implementação de cada estratégia e ao término de um ano; avaliar as variáveis associadas à vacinação; e avaliar os principais motivos de não vacinação entre os PS com indicação para tal. Métodos: Estratégias implementadas: divulgação, no boletim do hospital, de texto relembrando da necessidade de vacinação de coqueluche; reforço da necessidade da vacinação, via correio eletrônico, para as chefias de enfermagem das Divisões de Clínica Obstétrica, Neonatologia e Anestesia; aulas sobre a vacina dTpa nas reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; e vacinação ativa dos profissionais na Divisão de Clínica Obstétrica, Neonatologia e Anestesia. A cobertura vacinal foi avaliada ao fim de cada mês até abril de 2016, por meio do sistema informatizado de vacinação usado no CRIE-HC. Foi usado o modelo de regressão de Poisson com variância robusta para avaliação das variáveis associadas com a vacinação com dTpa. As razões de prevalência foram calculadas e seus intervalos de confiança de 95% estimados. Para avaliar os motivos de não vacinação, foram realizadas ligações telefônicas para os profissionais que não receberam a vacina e aplicado questionário padronizado. Resultados: Entre os 515 PS elegíveis para vacinação, 59 não possuíam registro no sistema informatizado de vacinação e foram excluídos. Assim, este estudo incluiu 456 PS. Após as intervenções, a cobertura vacinal com dTpa aumentou de 2,9% para 41,2%. As coberturas vacinais após a implementação de cada estratégia foram: 3,7% após publicação no Boletim do hospital; 10,5% após mensagem de correio eletrônico para as chefias de enfermagem; 16,2% após aula sobre a vacina em reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; 27,9% após vacinação ativa na Divisão de Clínica Obstétrica; 40,6% após vacinação ativa na Divisão de Neonatologia e 41,2% após vacinação ativa na Divisão de Anestesia. Na análise multivariada, ser médico (a), trabalhar nas Divisões de Clínica Obstétrica ou Anestesia e ter recebido a vacina de influenza de 2015 foram associados à vacinação com dTpa. Foi feito contato telefônico com 39 profissionais que não receberam a vacina em nosso serviço; apenas 9 (23%) referiram ter recebido a vacina em outros serviços; e dos 30 não vacinados, 27 (90%) alegaram desconhecimento da recomendação. Conclusões: Conhecimento sobre a doença e a recomendação de vacinação são importantes para aumentar a cobertura vacinal entre PS. Porém, mesmo sabendo do efeito cumulativo na cobertura vacinal a cada estratégia realizada, a vacinação ativa dos PS em seus locais de trabalho parece ter sido a estratégia que mais contribuiu para o aumento da cobertura. A cobertura vacinal final de dTpa permanece baixa e maiores esforços são necessários para aumentá-la
Introduction: The acellular pertussis vaccine for adults (Tdap) was introduced in the Brazilian National Immunization Program (PNI) in November 2014, being recommended for pregnant women and healthcare workers (HCWs) who have contact with pregnant women and newborns. From April to December 2015, interventions to raise Tdap coverage among HCWs of the Instituto Central do Hospital das Clínicas were implemented. Objective: To evaluate the cumulative vaccine coverage after each intervention; identify factors associated to Tdap vaccination among HCWs; and evaluate the main reasons for HCWs not receiving Tdap. Methods: Interventions implemented: a note on the hospital\'s internal newsletter, reminding HCWs of the importance of pertussis vaccination; email to the nurse´s teams leaders strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. The vaccine coverage was evaluated at the end of each month until April-2016. A multivariate Poisson regression model with robust error variance was used to evaluate variables associated with Tdap vaccination. Prevalence ratios (PR) and their 95%CI were estimated. To evaluate the reasons for HCWs not to be vaccinated, those who have not received Tdap were called by phone and a standard questionnaire was applied. Results: Among 515 HCWs eligible for immunization, 59 professionals were not registered in the vaccination data system and were excluded because information about Tdap vaccine could not be achieved. The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.9% to 41.2%. The vaccine coverage after each intervention was: 3.7% after a note on the hospital\'s internal newsletter; 10.5% after email to the nurse´s teams leaders strengthening vaccine recommendations; 16.2% after lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; 27.9% after on-site vaccination by mobile teams at the Obstetrics Clinic; 40.6% after on-site vaccination at the Neonatology Clinic and 41.2% after on-site vaccination at the Anesthesiology Clinic. In the multiple analysis, occupation, working place and having received influenza vaccination in 2015 were independently associated to Tdap vaccination. Thirty-nine HCWs that have not received Tdap were contacted by phone: 90% of them claimed they did not know the vaccine recommendation. Conclusions: Knowledge about pertussis and the recommendation of vaccination are important to raise vaccine coverage between HCWs. Even knowing the cumulative effect of each strategy on vaccine coverage, HCWs vaccination in their workplaces seems to be the most effective strategy in raising coverage. The final Tdap coverage remains low and greater efforts are needed to increase it

Plasmazellen gehören zu den Effektorzellen des adaptiven Immunsystems. Langlebige Plasmazellen tragen durch kontinuierliche Sekretion protektiver Antikörper wesentlich zum humoralen Gedächtnis bei und überleben hauptsächlich in spezialisierten Nischen des Knochenmarks. Bislang ist jedoch kein Marker bekannt, mit dessen Hilfe langlebige Plasmazellen eindeutig identifiziert werden können. Die vorliegende Arbeit befasst sich mit der molekularbiologischen, phänotypischen und funktionellen Charakterisierung von reifen Plasmazellen im gesunden humanen Knochenmark, die sich durch die differentielle Expression von CD19 unterscheiden. Dabei konnte festgestellt werden, dass CD19negative Plasmazellen durch eine vergleichsweise geringere Expression von CD45 und HLADR einen höheren Reifegrad aufweisen als CD19positive Plasmazellen. Zudem lässt die vermehrte Expression von CD28, Mcl1, Bcl2 sowie die schwächere Expression u.a. von CD95 darauf schließen, dass CD19negative Plasmazellen im Knochenmark eine bessere Überlebenskapazität besitzen als CD19positive Plasmazellen. Da beide Plasmazellpopulationen ähnliche Antigen-Spezifitäten aufweisen, Plasmazellen im Knochenmark von Säuglingen ausschließlich CD19 exprimieren und nach sekundärer Vakzinierung im Blut detektierbare Plasmablasten und Plasmazellen ebenfalls CD19 auf ihrer Oberfläche exprimieren, weist die Gesamtheit der Daten darauf hin, dass sich CD19negative Plasmazellen im Kindesalter in situ aus reifen CD19positiven Plasmazellen im Knochenmark entwickeln. Die CD19negative Plasmazellpopulation leistet durch hohe Halbwertszeit und Stabilität einen konstanten Beitrag zur Aufrechterhaltung des humoralen Gedächtnisses. Die CD19positive Plasmazellpopulation stellt hingegen eine flexible Komponente dar, die eine Anpassung der humoralen Immunität und des humoralen Gedächtnisses an aktuelle Herausforderungen auch im Erwachsenenalter ermöglicht.
Plasma cells are effector cells of the adaptive immune system. Humoral memory is sustained by long-lived plasma cells that continuously secrete protective antibodies and mostly reside in specialized niches in the bone marrow. So far, no marker is known that could distinguish long-lived plasma cells from short-lived ones. The present work addresses the biomolecular, phenotypical and functional characterization of mature plasma cells in healthy human bone marrow that differ in their expression of the surface marker CD19. CD19negative plasma cells showed higher maturity than CD19positive plasma cells as they expressed lesser amounts of CD45 and HLADR. Moreover, higher expression of CD28, Mcl1 and Bcl2 and lesser expression of CD95 argues for a better survival capacity of CD19negative plasma cells. Both plasma cell populations showed similar antigen specificities. All plasmablasts and plasma cells detectable in blood after secondary vaccination expressed CD19, as well as all plasma cells isolated from infant bone marrow. These results indicate that CD19negative plasma cells mainly develop during childhood by further differentiation of mature CD19positive plasma cells in situ in the bone marrow. CD19negative plasma cells represent a long-lived and stable component of the adaptive immune system and humoral memory, whereas the CD19positive plasma cell population displays a flexible element allowing for adaption of humoral immunity to new challenges throughout a lifetime.

Das humorale Immungedächtnis wird von reifen Plasmazellen des Knochenmarks vermittelt, welche bei Immunreaktionen aus aktivierten B-Lymphozyten gebildet werden. Dabei sind im Blut Plasmablasten als unmittelbare Vorläufer der Plasmazellen nachweisbar, die von dort aus in das Knochenmark einwandern. Anhand der durchflusszytometrischen Detektion spezifischer Plasmablasten gelang es hier, das simultane Auftauchen von Wellen neu generierter, migratorischer Plasmablasten und reifer, nicht-migratorischer Plasmazellen im Blut eine Woche nach einer Tetanusimpfung nachzuweisen. Plasmablasten und Plasmazellen lagen stets im Gleichgewicht vor, wodurch auf die stöchiometrische Mobilisierung reifer Plasmazellen des Knochenmarks durch systemisch induzierte Plasmablasten geschlossen wurde. Ein solcher Verdrängungsmechanismus wird hier erstmalig als Anpassungsmechanismus des humoralen Immungedächtnisses dargestellt, der die Aufnahme neuer Spezifitäten in das Gedächtnis unter Wahrung der Stabilität präexistierender Spezifitäten erlaubt. Anders als systemisch induzierte Plasmablasten, weisen Plasmablasten, die im immunologischen Ruhephase zirkulieren, Kennzeichen mukosaler Immunreaktionen auf: sie exprimieren IgA sowie die mukosalen Zellmigrationsrezeptoren alpha4beta7-Integrin und CCR10. Wahrscheinlich wandern sie in mukosale Plasmazelldepots ein und interferieren nicht mit den Plasmazellen des Knochenmarks, sodass die Stabilität des humoralen Gedächtnisses in der Ruhephase gewahrt bleibt. Eine Anpassung des humoralen Gedächtnisses findet somit nur im Rahmen systemischer Immunreaktionen statt. Bei splenektomierten Patienten und unter der B-Zell-Depletionstherapie bei Rheumapatienten bleiben mukosale Plasmablasten im Blut nachweisbar. Dies belegt deren autonome Bildung aus mukosalen, therapie-refraktären B-Zellen. Insgesamt wird hier eine bisher unbeachtete Komplexität menschlicher peripherer Plasmablasten und Plasmazellen und ihren Beziehungen zum humoralen Immungedächtnis dargestellt.
Humoral memory, i.e. persistence of specific antibody titers, is provided by plasma cells in the bone marrow, which are generated from activated B cells during immune responses. At this, immediate plasma cell precursors, the plasmablasts, migrate via the blood to the bone marrow. Using cytometric detection of antigen-specific plasmablasts, synchronous circulation of waves of recently generated, migratory plasmablasts and non migratory plasma cells with a mature phenotype was demonstrated one week after tetanus vaccination. Circulating plasmablast and plasma cell numbers were always in homeostasis, so that the stoichiometric mobilization of old bone marrow plasma cells by recently generated plasmablasts was hypothesized. This plasma cell replacement mechanism is herein described for the first time as an adaption mechanism of the humoral memory that allows incorporation of new antibody specificities while maintaining pre-existing ones. In immunological steady state, very low numbers of plasmablasts are detectable in any donor. These express IgA and receptors for mucosal homing, alpha4beta7 integrin and CCR10, and therefore most likely migrate into mucosal plasma cell depots and do not interfere with plasma cells of the bone marrow, preserving the stability of humoral memory during steady state. Hence, adaption of humoral memory is only possible during systemic immune reactions. Circulating mucosal plasmablasts produced during steady state remain detectable in patients with rheumatoid arthritis during B cell depletion therapy as well as in asplenic patients. Hence, this type of plasmablasts is self-sufficiently generated from mucosal B cells that are refractory to B cell depletion therapy. This work demonstrates a hitherto disregarded complexity of peripheral plasmablast and plasma cell subsets in healthy humans, with implications for the regulation of induction and maintenance of humoral memory.