Immunological Considerations Research Articles

Grasping time - longevity of vascularized composite allografts.

Despite significant advancements in the field of vascularized composite allotransplantation, challenges, particularly regarding the long-term viability and functionality of vascularized composite allotransplantation (VCA) grafts, persist. This paper provides a review of the current literature on the longevity of VCA grafts, focusing on factors influencing graft survival, immunological considerations and clinical outcomes. Longevity of VCA grafts is influenced by a variety of peri- and postoperative factors including cold ischemia time, human leukocyte antigen matching, environmental exposure, psychosocial factors, adherence, immunosuppression, and complications. Due to the limited number of VCA transplants performed and heterogenous reporting, direct correlation of single factors with VCA outcomes remains inconclusive. Indirect evidence, however, supports their importance. High immunosuppressive burden, frequent occurrence of acute and accumulating cases of chronic rejection remain a significant challenge of the field. Insights gained from this review aim to inform clinical practice and guide future research endeavors with the goal of ameliorating outcomes after VCA transplantation and facilitate wider use of VCA grafts for restoration of tissue defects.

Comparison of Autologous and Allogeneic Adipose-Derived Stem Cells in Kidney Transplantation: Immunological Considerations and Therapeutic Efficacy.

Regenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts' survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure.

Immunological Considerations for the Development of an Effective Herpes Vaccine.

Research is underway to develop a vaccine to prevent and cure infection from herpes simplex virus (HSV). It emphasizes the critical need for immunization to address public health issues and the shortcomings of existing treatment options. Furthermore, studies on the HSV vaccine advance the field of immunology and vaccine creation, which may help in the battle against other viral illnesses. The current lack of such a vaccine is, in part, due to herpes viral latency in sensory ganglions. Current vaccines rely on tissue-resident memory CD8+ T cells, which are known to provide protection against subsequent HSV reinfection and reactivation without correlating with other immune subsets. For that reason, there is no effective vaccine that can provide protection against latent or recurrent herpes infection. This review focuses on conventional methods for evaluating the efficacy of a herpes vaccine using differential CD8+ T cells and important unaccounted immune aspects for designing an effective vaccine against herpes.

Immunological and Safety Considerations When Selecting the Dose Formulation of a Purified Inactivated Zika Virus Vaccine (PIZV).

We previously reported the first-in-human assessment of three doses (2, 5, and 10 µg) of purified inactivated Zika virus vaccine (PIZV or TAK-426) in the Phase 1 ZIK-101 study (NCT03343626). Here, we report dose selection based on extended safety and immunogenicity data (6 months post-vaccination) and discuss considerations (e.g., immunological, historic, flavivirus immunological cross-reactions) for selecting a Zika virus (ZIKV) vaccine dose formulation. TAK-426 dose selection was conducted at the first interim analysis, and was based on cumulative safety data from both flavivirus-naïve (up to ≥28 days post-dose PD2) and flavivirus-primed participants (up to ≥28 days PD1), and on immunogenicity data from flavivirus-naïve participants only (at 28 days PD1 and 28 days PD2). The safety profile from TAK-426 recipients was compared to placebo recipients. Immunogenicity was assessed by geometric mean titer ratios of neutralizing anti-ZIKV antibodies and differences in seroconversion rates. There was no significant difference in safety between the three TAK-426 doses. The 10 μg dose provided the earliest and strongest immune response (with close to 100% seroconversion and higher antibody titers PD1 in flavivirus-naïve participants), and was well tolerated with acceptable safety profiles in both flavivirus-naïve and flavivirus-primed participants; this dose was selected for further development.

The Immunological Considerations in Patients With Thymoma: Lessons Beyond Resection

The Immunological Considerations in Patients With Thymoma: Lessons Beyond Resection

Immunologic Factors and Genomic Considerations in Recurrent Pregnancy Loss: A Review

Recurrent pregnancy loss (RPL), which is also known as repeated miscarriage, affects around 2-3% of women who are trying to conceive. While some factors contributing to RPL have been identified, the cause of almost half of all cases remains unknown. Immunological factors have been proposed as one of the potential causes of such miscarriages. However, it is hard to track the common factors leading to RPL since the individual genomic identity of aborted fetuses is different in a family like other siblings. The immunological factors involved in the pathogenesis of miscarriage generally result from either the function of the maternal immune system attributable to her genomic background or the fetal origination established by both maternal and paternal genomic backgrounds that constitute the fetal genome.

Hematologic Support in HIV Patients: Blood Transfusion Strategies and Immunological Considerations

HIV infection presents multifaceted challenges, particularly in managing hematologic complications that significantly impact patient well-being and prognosis. Hematologic manifestations such as anemia, thrombocytopenia, and coagulopathies are prevalent in individuals living with HIV, necessitating meticulous attention and specialized care. Among the array of interventions, blood transfusions play a pivotal role in addressing these hematologic complications. However, the complexities surrounding blood transfusion strategies in the context of HIV extend beyond mere hematologic support and delve into intricate immunological considerations. This paper aims to elucidate the nuanced landscape of hematologic support in HIV patients, focusing specifically on blood transfusion strategies and their immunological implications. The review encompasses an in-depth analysis of hematologic abnormalities commonly encountered in HIV, exploring the prevalence, etiology, and clinical impact of anemia, thrombocytopenia, and coagulopathies. Additionally, it examines the indications, safety measures, and challenges associated with blood transfusion therapy in this population. Furthermore, the paper delineates the intricate interplay between blood transfusions and the immunological milieu of HIV-infected individuals. It explores the immunomodulatory effects of transfusions, potential immune activation, and the impact on disease progression, while also addressing concerns regarding alloimmunization and the modulation of immune responses posttransfusion. By synthesizing current evidence and insights, this paper delineates the clinical outcomes, challenges, and controversies surrounding blood transfusion strategies in HIV care. It underscores the need for optimized transfusion practices tailored to the unique immunological landscape of HIV patients and highlights avenues for future research and advancements in clinical practice. In conclusion, this paper serves as a comprehensive resource elucidating hematologic support through blood transfusion strategies in HIV patients, providing a foundation for informed decision-making and paving the way for enhanced care paradigms in the management of hematologic complications in HIV. Keywords: Hematologic Support, HIV, Patients and Blood Transfusion

Respiratory Failure Due to Idiopathic Pneumonia Syndrome in a Pediatric Patient After Recipient-derived Allogeneic Chimeric Antigen Receptor T-Cell Therapy.

Idiopathic pneumonia syndrome (IPS) is a life-threatening complication of hematopoietic cell transplantation, but it is not clearly described following chimeric antigen receptor (CAR) T-cell therapy. We describe a child who developed IPS after receiving tisagenlecleucel for post-hematopoietic cell transplantation relapsed acute lymphoblastic leukemia and had a remarkable improvement after treatment with corticosteroids and etanercept. We discuss the implications of cytokine signaling in IPS and immunologic considerations of allogeneic CAR T cells. We anticipate that the incidence of IPS and other allogeneic phenomena will be observed more often as allogeneic CAR T cells are employed in more varied settings with more mismatched donors.

Clinical and Immunological Considerations of Monoclonal Antibody Therapy in COVID-19 A Review

Currently, effective methods for the prevention and treatment of coronavirus infections have not been developed. This could be attributed to the unique pathogenesis of the coronavirus infection and the rapid global spread of the pandemic, which have posed challenges to ongoing research efforts. Similar to other viral infections, coronavirus infection leads to the development and dissemination of the inflammatory process, resulting in viremia or the systemic spread of the infection. This uncontrolled inflammatory response is characterized by elevated levels of cytokines such as IFNy, IL-1, IL-6, and IL-12 in the bloodstream, transitioning the initial inflammatory reaction into a phase known as the cytokine storm. The cytokine storm is marked by severe clinical and laboratory manifestations. Consequently, it is crucial to implement appropriate therapies that target the uncontrolled inflammation induced by the virus rather than viremia itself. Hence, the aim of our study was to investigate the impact of monoclonal antibodies, specifically the medication "Kazirivimab + Imdevimab," which is a combination of recombinant monoclonal antibodies targeting the S-protein, on the clinical progression and laboratory parameters in patients with COVID-19.

Immunological considerations for laboratory staff and COVID-19 biosafety

The vulnerability of healthcare and laboratory to potential infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has thus far been analyzed through the lens of the acute phase of the pandemic, including remote-based work, as well as emergency settings that are different from routine healthcare operations. However, as lockdowns ease and activities return to an identifiable pre-pandemic routine, the safety considerations also require to shift accordingly. As laboratory workers are likely to continue being exposed to unidentified SARS-CoV-2 positive samples through routine blood collection and processing operations, coronavirus disease 2019 (COVID-19) might have to be re-considered as an occupational disease within this context. Additionally, as per many such occupational diseases, a surveillance system is implemented for the medium- and long-term. This manuscript presents the views on the possible surveillance scenarios for laboratory staff, viewed from an immunological and biosafety perspective.

An Overview of Gene Editing Modalities and Related Non-clinical Testing Considerations.

Gene therapy has become an important modality for a wide range of therapeutic indications with a rapid increase in the number of therapeutic candidates being developed in this field. Understanding the molecular biology underlying the gene therapy is often critical to develop appropriate safety assessment strategies. We aimed to discuss some of the commonly used gene therapy modalities and common preclinical toxicology testing considerations when developing gene therapies. Non-viral gene delivery methods such as electroporation, microinjection, peptide nanoparticles and lipid nanoparticles are deployed as innovative molecular molecular construct which are included in the design of novel gene therapies and the associated molecular biology mechanisms have become relevant knowledge to non-clinical toxicology. Viral gene delivery methodologies including Adenovirus vectors, Adeno-Associated virus vectors and Lentivirus gene therapy vectors have also advanced considerably across numerous therapeutic areas, raising unique non-clinical toxicology and immunological considerations. General toxicology, biodistribution and tumorigenicity are the pillars of non-clinical safety testing in gene therapies. Evaluating the tumorigenicity potential of a gene editing therapy often leverages molecular pathology while some translational challenges remain. Toxicology study design is entering a new era where science-driven customized approaches and program specific considerations have become the norm.

Mobilizing Public Interest in Vascularized Composite Allotransplantation: An Analysis of Online Traffic.

Despite growing public interest in and extensive media coverage of facial transplantation, a recent survey study found that only 63% of laypersons demonstrate basic awareness of the field.1 On February 3, 2021, our institution published a press release regarding our latest transplant recipient, who received a face and bilateral hands. We present this viewpoint to discuss our analyses of webpage traffic and Google trends, which illustrates the public’s curiosity regarding vascularized composite allotransplantation (VCA) and sheds light on how we may overcome the field’s key obstacles; in particular, donor pool expansion. Analysis of online traffic enables researchers to derive market intelligence by gauging public interest. Its relevance in transplantation was demonstrated by Gordon et al.,2 who used webpage traffic data to highlight the effectiveness of call-to-action campaigns for living kidney donors. We compared the online traffic of our facial transplantation program’s homepage during the week of the press release (February 2, 2021, to February 8, 2021) with that of the preceding week. A 1230.67% increase in visits to our facial transplantation program’s homepage (https://nyulangone.org/locations/face-transplant-program) was revealed. Most of the traffic (72.60%) was driven by natural searches, indicating organic interest from the public (Fig. 1). Such interest was further supported by Google trends showing the greatest annual spike in queries during the week of the press release (Fig. 2).Fig. 1.: Face transplant program webpage visits by acquisition channel in the week of the press release. “Organic search” refers to visitors who found our website using search tools such as Google. “Direct access” refers to visitors who accessed the webpage without clicking on a link. “Referring domains” refers to visitors who clicked on a link in other webpages, and “social media” refers to visitors coming from social media posts (eg, Facebook, Instagram).Fig. 2.: Google trends analysis. Graphical representation of Google queries in the United States for face transplant (dark purple) and face and hand transplant (light purple) between July 26, 2020, and July 11, 2021, demonstrating the maximum value for both relevant search terms occurred during the week of January 31, 2021, to February 6, 2021, coinciding with the press release. The y axis shows the normalized search frequency; each data point is divided by the total searches in a given geography and time range to compare relative popularity. The resulting numbers are scaled on a range of 0 to 100 based on a topic’s proportion to all searches on all topics. The x axis shows the time frame of relevant search results.Organ transplantation is hindered by a limited supply of donors; facial transplantation donor identification is uniquely challenging because of the stringent immunologic, cephalometric, and aesthetic considerations that must be taken into account.3 Moreover, unlike solid organs, facial transplantation donation requires a separate consent with the approval of a decedent’s family, further constricting the theoretical donor pool. Previous research has shown that 48% of Americans would be willing to donate their face.4 However, estimates show that only one-third of the U.S. population has completed advanced directives,5 and it is likely that significantly fewer have discussed facial transplantation donation with relevant family members. The general public, as a broad stakeholder, wields considerable power to advance the field of VCA. Educational interventions have proven successful at increasing public awareness and willingness to donate.1 The organic interest in VCA generated through public relations may be leveraged to inform and mobilize potential donors at the time of peak engagement. Moreover, public education could also be helpful in promoting legislative actions to reduce friction in the donation process. Given the spike in interest generated by our press release, timely provision of educational material and direct links to local donor registries would be crucial to make the best use of public interest. In summary, we found a substantial increase in traffic to our facial transplantation program’s webpage after issuing a press release on a successful face and bilateral hand transplant. Donor shortages remain one of the greatest challenges in the field of VCA. Spikes in interest represent unique opportunities that can be leveraged to educate the public, promote advocacy of the field, and expand the donor pool. ACKNOWLEDGMENT The authors thank the donor and recipient patients and families. DISCLOSURE The authors have no financial interest to declare in relation to the content of this article.

HYPEREOSINOPHILIA LEADS TO PRIMARY IMMUNODEFICIENCY DIAGNOSIS

<h3>Introduction</h3> In the absence of prior infections, idiopathic hypereosinophilia should prompt consideration of a primary immunodeficiency (PID). <h3>Case Description</h3> We present an 8-month-old previously healthy male admitted for persistent hypoxia and suspected bronchiolitis. This patient did not present with fever, weight loss, adenopathy, chronic rash, GI symptoms, or medication use. There was no travel history, sick contacts, or pertinent family history. Laboratory results were significant for negative viral panel and absolute eosinophil count > 34,000. Chest CT showed scattered ground glass opacities without cavitation or bronchiectasis. Bone marrow biopsy was negative for malignancy. T cell (beta) and B cell gene rearrangement studies were negative, as well as FIP1L1-PDFGFRA, FISH studies, and myelodysplastic panels. Cardiac workup, infectious/parasitic tests, tryptase, and B12 levels were normal. The patient was started on systemic steroids with dramatically improved hypereosinophilia. Workup revealed low IgG/IgA levels, with normal IgM. Vaccine titers to tetanus, diphtheria and Hib were absent, despite up-to-date immunizations. Genetic testing revealed a pathogenic mutation in the CD40L gene, indicating X-linked hyper IgM syndrome (HIGM). Pneumocystic jirovecii was confirmed with bronchoscopy. TMP-SMX treatment allowed for weaning off steroids. The patient was started on IVIG and is awaiting bone marrow transplant. <h3>Discussion</h3> HIGM often presents in infancy with increased susceptibility to sinopulmonary infections. Unlike other PIDs with clinical manifestations of atopy, HIGM does not often present with eosinophilia. Opportunistic infections, including PJP, may drive eosinophil production through antigenic stimulation of TH2 cells. This case illustrates the importance of immunologic considerations in patients with unexplained hypereosinophilia, even without a significant infectious history.

Projecting the SARS-CoV-2 transition from pandemicity to endemicity: Epidemiological and immunological considerations.

In this review, we discuss the epidemiological dynamics of different viral infections to project how the transition from a pandemic to endemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) might take shape. Drawing from theories of disease invasion and transmission dynamics, waning immunity in the face of viral evolution and antigenic drift, and empirical data from influenza, dengue, and seasonal coronaviruses, we discuss the putative periodicity, severity, and age dynamics of SARS-CoV-2 as it becomes endemic. We review recent studies on SARS-CoV-2 epidemiology, immunology, and evolution that are particularly useful in projecting the transition to endemicity and highlight gaps that warrant further research.

Improving Antibody Therapeutics by Manipulating the Fc Domain: Immunological and Structural Considerations.

Interactions between the crystallizable fragment (Fc) domain of antibodies and a plethora of cellular Fc receptors (FcRs) or soluble proteins form a critical link between humoral and innate immunity. In particular, the immunoglobulin G Fc domain is critical for the clearance of target cells by processes that include (a) cytotoxicity, phagocytosis, or complement lysis; (b) modulation of inflammation; (c) antigen presentation; (d) antibody-mediated receptor clustering; and (e) cytokine release. More than 30 Fc-engineered antibodies aimed primarily at tailoring these effects for optimal therapeutic outcomes are in clinical evaluation or have already been approved. Nonetheless, our understanding of how FcR engagement impacts various immune cell phenotypes is still largely incomplete. Recent insights into FcR biology coupled with advances in Fc:FcR structural analysis, Fc engineering, and mouse models that recapitulate human biology are helping to fill in existing knowledge gaps. These advances will provide a blueprint on how to fine-tune the Fc domain to achieve optimal therapeutic efficacy.

Immunological considerations and vaccines against COVID-19

The outbreak COVID-19 is considered as a revolution in history of biological science. SARS-CoV-2 is a main cause of COVID-19 having resemblance with MERS-CoV and SARS-CoV. The response of host to the infection of SARS-CoV is multiform and strong. Initially, an effective host defense in the lung is affiliated with disease resolution and mild symptoms. The escaping of virus from immune response can lead to damage the alveoli, systematic inflammation, and ineffective lung repair mechanism with associated organ dysfunction. The immunological responses are necessary to fight with the virus and an effective and a safe vaccine is needed to overcome the pandemic. The development of vaccine is progressing fast, billions of dollars committed with more than 200 candidates before even knowing whether a vaccine candidate will succeed.

Autoimmune pancreatitis and pancreatic cancer: Epidemiological aspects and immunological considerations

Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer, whereas such an association with autoimmune pancreatitis (AIP) is widely debated. Due to the rarity of the latter disorder, there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer, which do not seem to support it. However, these studies are affected by several limitations and, therefore, a link between AIP (and, specifically, type 1 AIP) and pancreatic cancer cannot be ruled out definitively on this basis. Moreover, several immunopathological aspects of type 1 AIP and, in general, immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression. In detail, Th2 immunological dominance, type 2 macrophage polarization and basophil infiltration observed in type 1 AIP, may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis, in addition to the immunosuppressive therapies that can be used in these patients.

Facial Transplantation: Principles and Evolving Concepts.

After studying this article, the participant should be able to: 1. Appreciate the evolution and increasing complexity of transplanted facial allografts over the past two decades. 2. Discuss indications and contraindications for facial transplantation, and donor and recipient selection criteria and considerations. 3. Discuss logistical, immunologic, and cost considerations in facial transplantation, in addition to emerging technologies used. 4. Understand surgical approaches and anatomical and technical nuances of the procedure. 5. Describe aesthetic, functional, and psychosocial outcomes of facial transplantation reported to date. This CME article highlights principles and evolving concepts in facial transplantation. The field has witnessed significant advances over the past two decades, with more than 40 face transplants reported to date. The procedure now occupies the highest rung on the reconstructive ladder for patients with extensive facial disfigurement who are not amenable to autologous reconstructive approaches, in pursuit of optimal functional and aesthetic outcomes. Indications, contraindications, and donor and recipient considerations for the procedure are discussed. The authors also review logistical, immunologic, and cost considerations of facial transplantation. Surgical approaches to allograft procurement and transplantation, in addition to technical and anatomical nuances of the procedure, are provided. Finally, the authors review aesthetic, functional, and psychosocial outcomes that have been reported to date.

Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings.

Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.