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[Introduction] Since the first description of gain of function (GOF) mutations in signal transducer and activator of transcription (STAT) 1, more than 300 patients have been described with a broad clinical phenotype including infections and severe immune dysregulation. Whilst Jak inhibitors (JAKinibs) have demonstrated benefits in several reported cases, their indications, dosing, and monitoring remain to be established., [Methods] A retrospective, multicenter study recruiting pediatric patients with STAT1 GOF under JAKinib treatment was performed and, when applicable, compared with the available reports from the literature., [Results] Ten children (median age 8.5 years (3–18), receiving JAKinibs (ruxolitinib (n = 9) and baricitinib (n = 1)) with a median follow-up of 18 months (2–42) from 6 inborn errors of immunity (IEI) reference centers were included. Clinical profile and JAKinib indications in our series were similar to the previously published 14 pediatric patients. 9/10 (our cohort) and 14/14 patients (previous reports) showed partial or complete responses. The median immune deficiency and dysregulation activity scores were 15.99 (5.2–40) pre and 7.55 (3–14.1) under therapy (p = 0.0078). Infection, considered a likely adverse event of JAKinib therapy, was observed in 1/10 patients; JAKinibs were stopped in 3/10 children, due to hepatotoxicity, pre-HSCT, and absence of response., [Conclusions] Our study supports the potentially beneficial use of JAKinibs in patients with STAT1 GOF, in line with previously published data. However, consensus regarding their indications and timing, dosing, treatment duration, and monitoring, as well as defining biomarkers to monitor clinical and immunological responses, remains to be determined, in form of international prospective multicenter studies using established IEI registries., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the Job Research Foundation (NY, USA); the Consejería de Salud de la Junta de Andalucía (SA0051/2020 to O.N.); Agencia de Innovación y Desarrollo de Andalucía (PI-0184–2018 to P.O); Instituto de Salud Carlos III, Madrid, Spain (Sara Borrell, CD20/00124 to P.B.L, Juan Rodés JR18/00042 to P.O, FIS PI19/01471 to O.N. and P.O); the projects PI18/00223, FI19/00208, and PI21/00211 to LA, integrated in the Plan Nacional de I + D + I and co-financed by the ISCIII—Subdirección General de Evaluación y Fomento de la Investigación Sanitaria—and the Fondo Europeo de Desarrollo Regional (FEDER), by Pla Estratègic de Recerca i Innovació en Salut (PERIS), Departament de Salut, Generalitat de Catalunya (SLT006/17/ 00199 to LA), by a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (IN[17]_BBM_CLI_0357) to LA, by a 2017 Beca de Investigación de la Sociedad Española de Inmunología Clínica Alergología y Asma Pediáatrica to LA, by a 2021 Beca de Investigación de la Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica to ADM and by the Ministry of Health, Czech Republic (NV18-05–00162 to M.B and NV19-05–00332 to V.K).

Background Sensitization to house dust mites (HDM) is frequent in patients with atopic dermatitis (AD). Objective To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus(Dpt) extract in patients with AD sensitized to HDM. Methods In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients aged ≥3 years, with SCORing Atopic Dermatitis (SCORAD) ≥15 and positive skin test and/or IgE to Dpt. Patients were stratified according to age ( > 15-point decrease in SCORAD. Secondary outcomes were decreases in SCORAD and objective SCORAD (O-SCORAD), Eczema Area and Severity Index (EASI), visual analog scale (VAS) for symptoms, pruritus scale; Investigator’s Global Assessment (IGA) 0/1; and decrease ≥4 points in Dermatology Life Quality Index (DLQI). Background therapy was maintained. Results A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% patients in HDM SLIT and placebo groups, respectively, showed > 15-point decrease in SCORAD (relative risk[RR]1.28, 95% confidence interval[CI] 0.89-1.83). Significant SCORAD decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference 20.4;95%CI 3.89-37.3); significant O-SCORAD decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference 21.3;95%CI 0.66-41.81); and more patients with IGA 0/1 in HDM SLIT group as compared to placebo group (14/35 vs 5/31;RR 2.63, 95%CI 1.09-6.39), were observed at 18 months. Conclusion Our results suggest that HDM SLIT may be effective in HDM sensitized patients as an add-on treatment for AD.

ObjectiveTo evaluate the clinical efficacy of a mixture of probiotics (Lactobacillus and Bifidobacterium) in children and adolescents with atopic dermatitis (AD) and the effects on sensitization, inflammation, and immunological tolerance.MethodsIn this double-blind, randomized, placebo-controlled clinical trial, we enrolled 60 patients aged between 6 months and 19 years with mild, moderate, or severe AD, according to the criteria proposed by Hanifin and Rajka. Patients were stratified to receive one gram per day of probiotics or placebo for 6 months. The primary outcome was a decrease in SCORing Atopic Dermatitis (SCORAD). Secondary outcomes were to assess the role of probiotics on the use of topical and oral medicines (standard treatment), serum IgE levels, skin prick test (SPT), and tolerogenic and inflammatory cytokines. Background therapy was maintained.ResultsForty patients completed the study (24 probiotics, 16 placebo). After treatment for six months, the clinical response was significantly better in the probiotics group; the SCORAD decreased [mean difference (MD) 27.69 percentage points; 95% confidence interval (CI), 2.44–52.94], even after adjustment for co-variables (MD 32.33 percentage points; 95%CI, 5.52–59.13), especially from the third month of treatment on. The reduction of the SCORAD in probiotic group persisted for three more months after the treatment had been discontinued, even after adjustment for co-variables (MD 14.24 percentage points; 95%CI, 0.78–27.70). Patients in the probiotics group required topical immunosuppressant less frequently at 6 and 9 months. No significant changes were found for IgE levels, SPT and cytokines.ConclusionsChildren and adolescents with AD presented a significant clinical response after 6 months with a mixture of probiotics (Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus paracasei, and Bifidobacterium lactis. However, this clinical benefit is related to treatment duration. Probiotics should be considered as an adjuvant treatment for AD.

Purpose: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and to identify factors influencing the outcome of infection.Methods: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. Results: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n=53). The infection presented mostly as asymptomatic (n=21) and mild (n=66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex related susceptibility and observed a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. Conclusion: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. Patients with complement deficiencies had milder COVID-19. However, the type of IEI was not a determining factor for severity. The severity of SARS-CoV-2 infection seems to be more related to older age, higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

Background: The hypothesis that early stimulation of the gut microbiota contributes to immune system balance has encouraged the use of probiotics to treat atopic dermatitis (AD), an immunological disorder characterized by chronic and relapsing skin inflammation, in several clinical studies. This study aimed to evaluate the clinical efficacy of a mixture of probiotics (Lactobacillus and Bifidobacterium) in children and adolescents with AD and the effects of probiotics on sensitization, inflammation, and immunological tolerance. Methods: In this double-blind, randomized, placebo-controlled clinical trial, children and adolescents (aged 2 to 19 years) received one gram (sachet) per day of probiotics or placebo for six months. SCOring of AD (SCORAD) index, serum IgE levels, skin prick test, tolerogenic and inflammatory cytokines were evaluated. Results: Forty patients were evaluated and clinical response was significantly better in the probiotic group as compared to the placebo group after treatment for six months; SCORAD decreased (95% CI, 2.44–52.94) even after adjustment for co-variables (95% CI, 5.52–59.13). Three months after the treatment was discontinued, improvement persisted in the probiotic group even after adjustment for co-variables (95% CI, 0.78– 27.70). IgE levels, skin prick test and cytokines did not differ between groups. Conclusions: AD children and adolescents treated with a mixture of probiotics (Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus paracasei, and Bifidobacterium lactis) for six months presented a significate SCORAD reduction as compared to placebo group. This probiotics mixture did not affect SPT and IgE levels, as well as inflammatory or tolerogenic cytokines. ClinicalTrials.gov #NCT02519556.

Primary immunodeficiency diseases (PIDs) comprise a genetically heterogeneous group of rare disorders that are caused by genetic defects or developmental defects of the immune system.

Ethnopharmacological relevance Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment. Aim of the study We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control. Patients and methods We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests. Results Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months. Conclusion The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo.

We report a novel homozygous JAK3 mutation in two female Brazilian SCID infants from two unrelated kindreds. Patient 1 was referred at 2 months of age due to a family history of immunodeficiency and the appearance of a facial rash. The infant was screened for TRECs (T-cell receptor excision circles) and KRECs (kappa-deleting recombination excision circles) for the assessment of newly formed naïve T and B cells respectively, which showed undetectable TRECs and normal numbers of KRECs. Lymphocyte immunophenotyping by flow cytometry confirmed the screening results, revealing a T-B+NK– SCID. The patient underwent successful HSCT. Patient 2 was admitted to an intensive care unit at 8 months of age with severe pneumonia, BCGosis, and oral moniliasis; she also had a positive family history for SCID but newborn screening was not performed at birth. At 10 months of age she was diagnosed as a T-B+NK– SCID and underwent successful HSCT. JAK3 sequencing revealed the same homozygous missense mutation (c.2350G>A) in both patients. This mutation affects the last nucleotide of exon 17 and it is predicted to disrupt the donor splice site. cDNA sequencing revealed skipping of exon 17 missing in both patients, confirming the predicted effect on mRNA splicing. Skipping of exon 17 leads to an out of frame deletion of 151 nucleotides, frameshift and creation of a new stop codon 60 amino acids downstream of the mutation resulting in a truncated protein which is likely nonfunctional.

(59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Gu� (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations:p.W361G,p.C282X,p.W483R,p.R226X,andp.Q93X),16 patientswith the commondeletionc.75_76 del.GTinexon2 ofNCF1 gene, and two patients with mutations in the CYBA gene. Conclusion. The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients. # 2015 Wiley Periodicals, Inc.

Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. Patients can present with severe, recurrent infections and noninfectious conditions. Among the latter, inflammatory manifestations are predominant, especially granulomas and colitis. In this article, we systematically review the possible mechanisms of hyperinflammation in this rare primary immunodeficiency condition and their correlations with clinical aspects.

The reactive-oxygen-species-(ROS)-generating-enzyme Nox2 is essential for leukocyte anti-microbial activity. However its role in cellular redox homeostasis and, consequently, in modulating intracellular signaling pathways remains unclear. Herein, we show Nox2 activation favors thioredoxin-1 (TRX-1)/p40phox interaction, which leads to exclusion of TRX-1 from the nucleus. In contrast, the genetic deficiency of Nox2 or its pharmacological inhibition with apocynin (APO) results in reductive stress after lipopolysaccharide-(LPS)-cell stimulation, which causes nuclear accumulation of TRX-1 and enhanced transcription of inflammatory mediators through nuclear-factor-(NF)-κB. The NF-κB overactivation is prevented by TRX-1 oxidation using inhibitors of thioredoxin reductase-1 (TrxR-1). The Nox2/TRX-1/NF-κB intracellular signaling pathway is involved in the pathophysiology of chronic granulomatous disease (CGD) and sepsis. In fact, TrxR-1 inhibition prevents nuclear accumulation of TRX-1 and LPS-stimulated hyperproduction of tumor-necrosis-factor-(TNF)-α by monocytes and neutrophils purified from blood of CGD patients, who have deficient Nox2 activity. TrxR-1 inhibitors, either lanthanum chloride (LaCl3) or auranofin (AUR), also increase survival rates of mice undergoing cecal-ligation-and-puncture-(CLP). Therefore, our results identify a hitherto unrecognized Nox2-mediated intracellular signaling pathway that contributes to hyperinflammation in CGD and in septic patients. Additionally, we suggest that TrxR-1 inhibitors could be potential drugs to treat patients with sepsis, particularly in those with CGD.

Implementing precise techniques in routine diagnosis of chronic granulomatous disease (CGD), which expedite the screening of molecular defects, may be critical for a quick assumption of patient prognosis. This study compared the efficacy of single-strand conformation polymorphism analysis (SSCP) and high-performance liquid chromatography under partially denaturing conditions (dHPLC) for screening mutations in CGD patients. We selected 10 male CGD patients with a clinical history of severe recurrent infections and abnormal respiratory burst function. gDNA, mRNA and cDNA samples were prepared by standard methods. CYBB exons were amplified by PCR and screened by SSCP or dHPLC. Abnormal DNA fragments were sequenced to reveal the nature of the mutations. The SSCP and dHPLC methods showed DNA abnormalities, respectively, in 55% and 100% of the cases. Sequencing of the abnormal DNA samples confirmed mutations in all cases. Four novel mutations in CYBB were identified which were picked up only by the dHPLC screening (c.904 insC, c.141+5 g>t, c.553 T>C, and c.665 A>T). This work highlights the relevance of dHPLC, a sensitive, fast, reliable and cost-effective method for screening mutations in CGD, which in combination with functional assays assessing the phagocyte respiratory burst will contribute to expedite the definitive diagnosis of X-linked CGD, direct treatment, genetic counselling and to have a clear assumption of the prognosis. This strategy is especially suitable for developing countries.

Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens orAspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas. Fil: Cabral Marques, Otavio. Universidade de Sao Paulo; Brasil Fil: Klaver, Stefanie. Universidade de Sao Paulo; Brasil Fil: Schimke, Lena F. Universidade de Sao Paulo; Brasil Fil: Ascendino, Évelyn H. Universidade de Sao Paulo; Brasil Fil: Khan, Taj Ali. Universidade de Sao Paulo; Brasil Fil: Pereira, Paulo Vítor Soeiro. Universidade de Sao Paulo; Brasil Fil: Falcai, Angela. Universidade de Sao Paulo; Brasil Fil: Vargas Hernández, Alexander. Instituto Politécnico de México; México Fil: Santos-Argumedo, Leopoldo. Instituto Politécnico de México; México Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Moreira, Ileana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Seminario, Gisela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Di Giovanni, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Raccio, Andrea Gómez. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Porras, Oscar. Hospital Nacional de Niños, “Dr. Carlos Sáenz Herrera”; Costa Rica Fil: Weber, Cristina Worm. Pediatric Allergy & Immunology Clinic; Brasil Fil: Ferreira, Janaíra Fernandes. Albert Sabin Hospital; Brasil Fil: Tavares, Fabiola Scancetti. Hospital de Base do Distrito Federal; Brasil Fil: de Carvalho, Elisa. Hospital de Base do Distrito Federal; Brasil Fil: Valente, Claudia França Cavalcante. Hospital de Base do Distrito Federal; Brasil Fil: Kuntze, Gisele. Integrated Center of Pediatric Specialties; Brasil Fil: Galicchio, Miguel. Hospital de Niños ; Argentina Fil: King, Alejandra. Hospital ; Chile Fil: Rosário Filho, Nelson Augusto. Universidade Federal do Paraná; Brasil Fil: Grota, Milena Baptistella. Universidade Estadual de Campinas; Brasil Fil: dos Santos Vilela, Maria Marluce. Universidade Estadual de Campinas; Brasil Fil: Di Gesu, Regina Sumiko Watanabe. Conceição Children’s Hospital; Brasil Fil: Lima, Simone. Childrens Hospital ; Brasil Fil: de Souza Moura, Leiva. Childrens Hospital ; Brasil Fil: Talesnik, Eduardo. Pontificia Universidad Católica de Chile; Chile Fil: Mansour, Eli. Universidade Estadual de Campinas; Brasil Fil: Roxo Junior, Pérsio. Universidade de Sao Paulo; Brasil Fil: Aldave, Juan Carlos. Hospital Nacional ; Perú Fil: Goudouris, Ekaterine. Universidade Federal do Rio de Janeiro; Brasil Fil: Pinto Mariz, Fernanda. Universidade Federal do Rio de Janeiro; Brasil Fil: Berrón Ruiz, Laura. Instituto Nacional de Pediatría; México Fil: Staines Boone, Tamara. Unidad Médica de Alta Especialidad #25; México Fil: Calderón, Wilmer O. Córdova. Clínica Montefiori; Perú Fil: del Carmen Zarate Hernández, María. Universidad Autónoma de Nuevo León; México Fil: Grumach, Anete S.. Universidade Federal do ABC; Brasil Fil: Sorensen, Ricardo. Children’s Hospital of New Orleans; Estados Unidos Fil: Durandy, Anne. Inserm; Francia Fil: Torgerson, Troy R.. University of Washington; Estados Unidos Fil: Carvalho, Beatriz Tavares Costa. Universidade de Sao Paulo; Brasil Fil: Espinosa Rosales, Francisco. Instituto Nacional de Pediatría; México Fil: Ochs, Hans D.. University of Washington; Estados Unidos Fil: Condino Neto, Antonio. Universidade de Sao Paulo; Brasil

A utoimmune hepatitis (AIH) is characterized by female predominance, hypergammaglobulinemia, autoantibodies, and a good response to immunosuppression. Its etiology is unknown. A model for its pathogenesis is that environmental triggers, associated with failure of immunological tolerance mechanisms and genetic predisposition, may contribute to the induction of a T-cell–mediated immune response against hepatic antigens, triggering a necroinflammatory and fibrotic process (1). Among these triggering agents are some drugs, toxins, and viral infections (hepatitis A-B-C, Epstein-Barr, Coxsackie, Hantavirus, herpes simplex, and measles). Molecular sequences that are shared among viruses and autoproteins may trigger autoimmune processes (2,3). Infectious agents such as Escherichia coli, mycobacteria, chlamydia, Helicobacter species, lactobacilli, Novosphingobium aromaticivorans, and betaretroviruses may elicit loss of immunological tolerance and induce primary biliary cirrhosis (4), and bacteria such as Coxiella burnetii (2) and Brucella abortus may induce overlap syndrome (AIH and primary biliary cirrhosis) (5). We report a unique case of coexistent leprosy and AIH in a child. A 9-year-old girl originally from Sao Luiz (northern region of Brazil) and now living in Ribeirao Preto (state of Sao Paulo) had been presenting with hypochromic lesions on arms and legs for 1 year. Two months before referral to our service, she had received a histopathological diagnosis of leprosy. Investigation of the patient revealed altered hepatic enzymes. Mother and father had a history of treatment of paucibacillary and multibacillary leprosy, respectively. Physical examination revealed no jaundice, annular plaques with erythema-infiltrated borders on arms and legs associated with paresthesia, and mild hepatomegaly, but no splenomegaly or lymphadenopathy. Laboratory tests: aspartate aminotransferase 363 U/L (RV< 32 U/L); alanine aminotransferase 419 U/L (RV< 31 U/L);g-glutamyl transpeptidase 36 U/L (RV 11–50 U/L); alkaline phosphatase 1129 U/L (RV< 645 U/L); albumin 4.1 g/dL;g-globulin 1.64 g/dL; serum immunoglobulins (immunoglobulin [Ig] G 1150.0 mg/dL [mean for the age 892 mg/dL], IgA 131.0 mg/dL [mean for the age 153 mg/dL], IgM 187.0 mg/dL [mean for the age 90 mg/dL]); normal bilirubin levels; negative anti-nuclear antigen, anti-mitochondrial, anti-liver-kidney-microsome, anti-human T

Severe Combined Immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency (PID). Complications of BCG vaccination, especially disseminated infection and its most severe forms, are known to occur in immunodeficient patients, particularly in SCID. A carefully taken family history before BCG injection as well as delaying vaccination if PID is suspected could be a simple and effective method to avoid inappropriate vaccination of an immunodeficient child in some cases until the prospect of newborn screening for SCID has been fully developed. We describe a patient with a very early diagnosis of SCID, which was suspected on the basis of the previous death of two siblings younger than one year due to severe complications secondary to the BCG vaccine. We suggest that a family history of severe or fatal reactions to BCG should be included as a warning sign for an early diagnosis of SCID.