Visceral Leishmaniasis Revealing Undiagnosed Inborn Errors of Immunity.

Visceral Leishmaniasis (VL) is a potentially fatal disease and may be associated with primary or acquired immunodeficiencies. There are few reports, in the literature, of inborn errors of immunity. Here, we report two cases of VL as a marker of inborn errors of immunity, namely, GATA2 and RAB27A deficiency. Our data suggest that VL patients should be screened for primary immunodeficiency, particularly in cases of VL relapse.

Impact of Treatment with Ustekinumab on Severe Infections in a Patient with Uncontrolled Psoriasis and Late-Onset Combined Primary Immunodeficiency: Case Report.

A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease was attended in the Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to the failure of other treatments (phototherapy, oral acitretin) for psoriasis and a Psoriasis Area Severity Index >10. We evaluated the impact of treatment with ustekinumab on severe infectious diseases in a patient with uncontrolled psoriasis and LOCID followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, cultures of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation; pathogenic variants in genetic sequencing, and clinically significant variants in the whole exome for primary immunodeficiencies were not detected. The main infections before and after treatment with ustekinumab were chronic sinusitis and gastroenteritis. The patient was infected with COVID-19, dengue (twice) and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence the susceptibility of the patient with LOCID to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease.

Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with Haemophilus influenzae Meningitis in a Newborn.

Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2).

INTRODUCTION: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. PATIENTS AND METHODS: This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. RESULTS: Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. CONCLUSION: The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Visceral Leishmaniasis Revealing Undiagnosed Inborn Errors of Immunity

ABSTRACT Visceral Leishmaniasis (VL) is a potentially fatal disease and may be associated with primary or acquired immunodeficiencies. There are few reports, in the literature, of inborn errors of immunity. Here, we report two cases of VL as a marker of inborn errors of immunity, namely, GATA2 and RAB27A deficiency. Our data suggest that VL patients should be screened for primary immunodeficiency, particularly in cases of VL relapse.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

A rare association between factor H deficiency and lupus: Case report and experimental treatment with curcumin.

Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. FH deficiency is a rare condition that causes unregulated C3 consumption, leading to an increased susceptibility to infections and glomerulopathies. Our previous studies have demonstrated a FH deficient patient carrying a c.452G > A, p.R127H FH mutation which leads to a misfolded protein and its retention in the endoplasmic reticulum. In his cultured fibroblasts, FH-delayed secretion was partially rescued when treated with curcumin, and once secreted, exhibited normal regulatory function. Here, we report a childhood-onset systemic lupus erythematosus (cSLE) in this FH deficient patient and the results of experimental treatment with curcumin aiming to rescue FH secretion and regulatory activity.

Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report.

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and esophageal rupture by candida infection: A case report and review.

We probably describe the first report of esophageal rupture in a patient with autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED, OMIM # 240300), who had candida esophagitis as the main feature for decades. Strong evidence shows that this rupture may have been caused directly and indirectly by chronic candidiasis. In this way, we demonstrate how severe and harmful the persistent esophageal candidiasis can cause in the esophagus, especially in immunodeficient patients.

Posicionamento da ASBAI sobre a vacinação de crianças de 5 a 11 anos contra a COVID-19 com a vacina Comirnaty/ Pfizer/BioNTech ­ 27/12/2021 / ASBAI's position on vaccination of children aged 5 to 11 years against COVID-19 with the Comirnaty/Pfizer/BioNTech vaccine ­ 12/27/2021

A Associação Brasileira de Alergia e Imunologia (ASBAI) se manifesta totalmente favorável à imunização contra a COVID-19 em indivíduos entre 5 e 11 anos, para a proteção não somente deste grupo, mas também de seus conviventes. A vacinação de crianças, demonstrada sua eficácia e segurança, é fundamental para o controle da circulação do vírus e proteção de indivíduos cuja resposta vacinal pode não ocorrer de modo eficiente, como os imunocomprometidos e idosos. A imunização de pessoas entre 5 e 11 anos deve ser uma estratégia de saúde pública fundamental para o controle da pandemia que nos assola desde março de 2020 com todas as suas graves consequências para a saúde pública e a economia.

The Brazilian Association of Allergy and Immunology (ASBAI) is totally in favor of immunization against COVID-19 in individuals between 5 and 11 years old, for the protection not only of this group, but also of their cohabitants. The vaccination of children, once its efficacy and safety has been demonstrated, is essential for controlling the circulation of the virus and protecting individuals whose vaccine response may not occur efficiently, such as the immunocompromised and the elderly. The immunization of people between the ages of 5 and 11 must be a fundamental public health strategy to control the pandemic that has been plaguing us since March 2020 with all its serious consequences for public health and the economy.

Diagnosis, treatment and maxillofacial rehabilitation in rhinocerebral mucormycosis patient: A case report and review of the literature.

Mucormycosis is an aggressive, rare and opportunistic infectious disease, with a high mortality rate. Etiologic agents are filamentous fungi, and infection among humans normally occurs through spore inhalation. A 61-year-old male individual, presenting left eye amaurosis, dark epistaxis, hyperalgesia and malodor underwent clinical examination, which detected ulcerative lesion and wide bone exposure in the hard palate and alveolar ridge. Direct microbiological examination, microbiological culture and lesion biopsy were performed. Non-septate smooth fungal hyphae forming right angles with each other were observed through the direct microbiological examination. Microbiological culture revealed fast-growing fungal colonies with cottony texture, identified as Rhizopus sp. Histopathological examination exhibited necrosis areas, intense mononuclear inflammatory infiltrate and bulky hyphae, thus concluding the mucormycosis diagnosis. Amphotericin B antifungal therapy and surgical intervention were adopted as treatment. The patient was then rehabilitated with maxillofacial prosthesis, subsequently to the healing of the surgical wound.

Evaluation of IFN-γ secretion after stimulation with C. neoformans and C. gattii antigens in individuals with frequent exposure to the fungus.

In this study we produced antigenic extracts from prototypical strains of C. neoformans (VNI-VNIV) and C. gattii (VGI-VGIV) and tested IFN-γ secretion by Elispot. Antigens from the eight Cryptococcus molecular types (VNI -VNIV and VGI - VGIV) were obtained after capsule reduction. IFN-γ secretion by Elispot method were stimulated with C. neoformans and C. gattii antigens. Peripheral blood mononuclear cells of fourteen healthy control subjects, being: five ecotourists, two mycologists, three poultry keepers, and four individuals without reports of exposure to the fungus. We observed a significant increase in IFN-γ secretion in the group of ecotourists, mycologists and bird keepers in relation to the group of individuals without reports of occupational exposures to these agents. Our results suggest the significant increase in IFN-γ secretion may be related to the continuous exposure of these groups of individuals to the fungus, as well as to the specific antigen memory immune response developed during exposure to Cryptococcus.

A Critical Review on the Standardization and Quality Assessment of Nonfunctional Laboratory Tests Frequently Used to Identify Inborn Errors of Immunity.

Inborn errors of immunity (IEI), which were previously termed primary immunodeficiency diseases, represent a large and growing heterogeneous group of diseases that are mostly monogenic. In addition to increased susceptibility to infections, other clinical phenotypes have recently been associated with IEI, such as autoimmune disorders, severe allergies, autoinflammatory disorders, benign lymphoproliferative diseases, and malignant manifestations. The IUIS 2019 classification comprises 430 distinct defects that, although rare individually, represent a group affecting a significant number of patients, with an overall prevalence of 1:1,200-2,000 in the general population. Early IEI diagnosis is critical for appropriate therapy and genetic counseling, however, this process is deeply dependent on accurate laboratory tests. Despite the striking importance of laboratory data for clinical immunologists, several IEI-relevant immunoassays still lack standardization, including standardized protocols, reference materials, and external quality assessment programs. Moreover, well-established reference values mostly remain to be determined, especially for early ages, when the most severe conditions manifest and diagnosis is critical for patient survival. In this article, we intend to approach the issue of standardization and quality control of the nonfunctional diagnostic tests used for IEI, focusing on those frequently utilized in clinical practice. Herein, we will focus on discussing the issues of nonfunctional immunoassays (flow cytometry, enzyme-linked immunosorbent assays, and turbidimetry/nephelometry, among others), as defined by the pure quantification of proteins or cell subsets without cell activation or cell culture-based methods.

Vacinas COVID-19 e outros imunobiológicos ­ intervalos preconizados / COVID-19 vaccines and other immunobiological drugs ­ recommended intervals

Com o início do programa de vacinação contra a COVID-19 no Brasil, surgiu uma série de questionamentos relacionados ao uso dos imunizantes. Neste documento, o grupo de estudo da COVID-19 da Associação Brasileira de Alergia e Imunologia (ASBAI) avalia as evidências científicas e se posiciona em relação aos intervalos preconizados entre a administração das vacinas contra o SARS-CoV-2 e dos imunobiológicos.

With the beginning of the COVID-19 vaccination program in Brazil, a series of questions related to the use of vaccines arose. In this document, the COVID-19 study group of the Brazilian Association of Allergy and Immunology (ASBAI) assesses the scientific evidence and takes a stand for the recommended intervals between the administration of SARS-CoV-2 vaccines and that of immunobiological drugs.

Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature.

We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.

Reinfecções pelo SARS-CoV-2: fato ou fake ? Implicações para a resposta vacinal / Reinfection with SARS-CoV-2: fact or fake? Implications for vaccine response

Há evidências atuais de que a reinfecção pelo SARS-CoV-2 é uma realidade, mas na grande maioria das situações não houve investigação que permitisse sua perfeita caracterização, sendo confirmados poucos casos. Em situações de real reinfecção, esta ocorreu, em sua grande maioria, por variantes do vírus, com diversas mutações, usualmente na proteína da espícula viral, em profissionais de saúde altamente expostos, ou em portadores de imunodeficiências, tanto primárias quanto secundárias. Ressaltamos que as vacinas podem ser modificadas com relativa facilidade, mas a capacidade de fabricação e de distribuição pelo mundo será capaz de acompanhar a demanda por vacinação em massa de forma eficiente? Neste manuscrito, a comissão de estudo da COVID-19 da ASBAI analisa criticamente o conhecimento atual sobre a reinfecção pelo SARS-CoV-2.

There is current evidence that reinfection with SARS-CoV-2 is a reality, but there is also a lack of investigation that would allow its perfect characterization, and few cases have been confirmed. Real reinfections occurred mostly with variants of the virus, with several mutations, usually in the viral spike protein, in highly exposed health professionals or in patients with immunodeficiencies, both primary and secondary. We emphasize that vaccines can be modified relatively easily, but will the manufacturing and distribution capacity around the world be able to keep up with the demand for mass vaccination efficiently? The ASBAI COVID-19 study commission critically analyzes in this manuscript the current knowledge about SARS-CoV-2 reinfection.

Alergias e vacinas contra a COVID-19 / Allergies and vaccines against COVID-19

As vacinas são reconhecidas como uma das conquistas do século passado de maior impacto em Saúde Pública, reduzindo de modo significativo a morbidade e mortalidade associadas a grande número de doenças infecciosas. No entanto, em casos raros, as vacinas podem causar doença ou eventos adversos pós-vacinação (EAPV). Os imunologistas clínicos e alergistas possuem um papel muito importante nesse momento em que mundialmente buscamos imunizar a população contra a COVID- 19. Eles devem fornecer apoio aos indivíduos orientando sobre o diagnóstico e tratamento de EAPV, incluindo anafilaxia, e, ainda, apoiar e encorajar os pacientes a se vacinarem, mesmo após eventos adversos, desde que leves ou moderados.

Vaccines are known as one of the achievements of the last century with greatest impact on public health, significantly reducing morbidity and mortality associated with a large number of infectious diseases. However, in rare cases, vaccines may cause disease or adverse events following immunization. Clinical immunologists and allergists have a very important role in the worldwide vaccination against COVID-19. They should provide support to individuals by advising on the diagnosis and treatment of adverse events following immunization, including anaphylaxis, and also support and encourage patients to be vaccinated, even after adverse events, as long as they are mild or moderate.

Vacinas contra a COVID-19 e os erros inatos da imunidade (ou imunodeficiências primárias) / COVID-19 vaccines and inborn errors of immunity (or primary immunodeficiencies)

Desde o início da pandemia de COVID-19 iniciou-se a corrida por uma imunização ativa, eficaz e segura. Todas as vacinas desenvolvidas até o momento vêm demostrando boa eficácia na prevenção de casos graves de COVID-19, de hospitalizações e mortes. Muitos pacientes com erros inatos da imunidade (EII) não terão capacidade de desenvolver uma resposta imune semelhante ao indivíduo imunocompetente. Esses pacientes foram incluídos nos grupos prioritários definidos pelo Ministério da Saúde, como pessoas entre 18 a 59 anos com uma ou mais das comorbidades, incluindo as imunodeficiências primárias. Eles podem e devem receber as vacinas em uso contra o SARS-CoV-2, mas nem sempre apresentarão uma resposta imunológica satisfatória e protetora, e, portanto, seus contactantes também devem ser vacinados.

Since the beginning of the COVID-19 pandemic, the race for an active, effective, and safe immunization has started. All vaccines developed to date have shown good efficacy in preventing serious cases of COVID-19, hospitalization, and death. Many patients with inborn errors of immunity will not be able to develop an immune response similar to that of immunocompetent individuals. These patients were included in the priority groups defined by the Brazilian Ministry of Health, as people between 18 and 59 years of age with one or more comorbidities, including primary immunodeficiencies. They can and should receive the vaccines in use against SARS-CoV-2, but they will not always have a satisfactory and protective immune response, and, therefore, those in direct contact with them should also be vaccinated.

Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature

Abstract We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.