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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).

Abstract Background IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing. Case presentation Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127−/CD4+/CD25+/FOXP3+—396 cells—63%) and a pathogenic mutation in FOXP3 gene (c.1150G>A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome. Conclusions IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.

Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.

Background: : Familial Mediterranean Fever (FMF) is the most common form of genetic autoinflammatory disease worldwide. In turn, selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency, yet most patients remain asymptomatic. Case Presentation: A Jewish Brazilian female came to our attention due to recurrent inflammatory febrile episodes since very early in life, initially attributed to unexplained infections linked to SIgAD. At the age of 15 years, disabling buttock pain prompted a sacroiliac MRI, which demonstrated sacroiliitis. Direct genetic sequencing of the MEFV gene confirmed the diagnosis of FMF. After severe gastrointestinal intolerance to colchicine was observed, canakinumab achieved clinical and radiological control, enabling the reinstatement of colchicine. Conclusion: Here we report the first case of concomitant FMF and SIgAD in a Brazilian patient, highlighting the relevance of these comorbidities in the patient's diagnosis and follow-up. This coincidental association also provides insight into interactions between serum and mucosal IgA and the pyrin inflammasome in the control of inflammation and gut dysbiosis.

Abstract Background Deficiency of the natural antagonist of interleukin-1 was first described in 2009 and so far 20 patients has been reported. In Brazil just two cases have been reported both carrying the same homozygous 15 bp deletion. Blocking interleukin-1 has changed rate survival for DIRA patients. The use of anakinra and rilonacept has been reported safe and efficient, whereas the selective blockade of interleukin-1 beta, using the monoclonal antibody canakinumab has been reported in a single case only. Case presentation Here we report a case of a 7 years old Brazilian boy that presented with recurrent episodes of systemic inflammation with severe disabling osteomyelitis with mild pustular skin rash. A Next Generation Sequencing gene panel allowed to detect two pathogenic mutations in the IL1RN gene, described in compound heterozygosity. Corticosteroids was effective in controlling inflammation and anti-IL1 beta blocker triggered disease flare. Complete clinical control could be achieved using IL-1 receptor antagonist. Conclusions DIRA is a severe, life threatening autoinflammatory condition with low numbers of patients described all over the world. The mutation p.Asp72_Ile76del in IL1RN is presented in all Brazilian DIRA patients already described and p.Q45* (rs1019766125) is a new mutation affecting the IL1RN gene. Following the pathogenesis of DIRA, blocking both subunits of interleukin one as well as antagonizing the receptor using anakinra or rilonacept seems to be effective. There is just one report using canakinumab for the treatment of DIRA and this is the first report of disease flare using this drug.

ABSTRACT Introduction: although it is a rare disease, common variable immunodeficiency (CVID) stands out as the most frequent primary symptomatic immunodeficiency. Carriers are prone to a variety of recurrent bacterial infections, in addition to the risk of developing autoimmune diseases and neoplasms including gastric cancer (GC). Despite the recognized risk, there are no specific standardized protocols for the management of GC in these patients, so the reported oncological results are varied. Thus, this study aims to describe the clinicopathological characteristics and prognosis of patients with CVID undergoing surgical treatment of GC. Methods: all patients with GC undergoing surgical treatment between 2009 and 2020 were retrospectively evaluated. Later, patients diagnosed with CVID were identified and this group was compared with the remaining patients without any immunodeficiency. Results: among the 1101 patients with GC evaluated in the period, 10 had some type of immunodeficiency, and 5 were diagnosed with CVID. Patients with CVID had younger age, lower BMI, and smaller lesions compared to those without CVID. Four patients underwent curative gastrectomy and one patient underwent jejunostomy. Two patients died (1 palliative and 1 curative) and one patient had disease recurrence. There was no statistically significant difference regarding the incidence of postoperative complications and survival between the evaluated groups. Conclusion: the CVID incidence in patients with GC undergoing surgical treatment was 0.5%, occurring at a less advanced age, but with no difference regarding surgical and oncological results.

ABSTRACT In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil.