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Patients with inborn errors of immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data of humoral and cellular responses combination on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patients in Argentina. The study cohort included adults and pediatric IEI patients (n = 118) and age-matched healthy controls (HC) (n = 37). B cell response was evaluated by measuring IgG anti-spike/receptor binding domain (S/RBD) and anti-nucleocapsid(N) antibodies by ELISA. Neutralization antibodies were also assessed with an alpha-S protein-expressing pseudo-virus assay. The T cell response was analyzed by IFN-γ secretion on S- or N-stimulated PBMC by ELISPOT and the frequency of S-specific circulating T follicular-helper cells (TFH) was evaluated by flow cytometry.No moderate/severe vaccine-associated adverse events were observed. Anti-S/RBD titers showed significant differences in both pediatric and adult IEI patients versus the age-matched HC cohort (p < 0.05). Neutralizing antibodies were also significantly lower in the patient cohort than in age-matched HC (p < 0.01). Positive S-specific IFN-γ response was observed in 84.5% of IEI patients and 82.1% presented S-specific TFH cells. Moderna vaccines, which were mainly administered in the pediatric population, elicited a stronger humoral response in IEI patients, both in antibody titer and neutralization capacity, but the cellular immune response was similar between vaccine platforms. No difference in humoral response was observed between vaccinated patients with and without previous SARS-CoV-2 infection.In conclusion, COVID-19 vaccines showed safety in IEI patients and, although immunogenicity was lower than HC, they showed specific anti-S/RBD IgG, neutralizing antibody titers, and T cell-dependent cellular immunity with IFN-γ secreting cells. These findings may guide the recommendation for a vaccination with all the available vaccines in IEI patients to prevent COVID-19 disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antibody deficiencies (AD) are characterized by low or absent immunoglobulin levels or the inability to develop a specific antibody response. They are classified in primary (PAD) when there is an intrinsic immune defect, or secondary (SAD) to other diseases or drugs. The aim of our study was to review the evolutio n of AD assisted at the Immunology Unit, Hospital Durand between 1982 and 2020, divided into two periods: Period I (1982-2009) and Period II (2010-2020); to evaluate their growth, epidemiologic features and treatment options. A total of 205 patients were identified, 176 (85.8%) with PAD and 29 (14.2%) with SAD. The most frequent PAD were common variable immunodeficiency in 104 (59%) patients, X linked agammaglobulinemia in 17 (9.6%) and selective IgA deficiency in 26 (14.8%). Genetic defects were found in 25 (14.2%) patients with PAD. SAD cases were associated with rituximab in 21 (72.4%) subjects, haematological disease in three (10.2%) and with antiepileptic drugs in other three; 161 (78.5%) patients were treated with immunoglobulins, 140 (87%) PAD y 21 (13%) SAD; 152 (94.4%) received intravenous immunoglobulins and nine (5.6%) subcutaneous immunoglobulins. Thirty (19.7%) patients treated at first with intravenous immunoglobulins changed to subcutaneous formulations. The increase in number of patients between both periods was greater than 250%, and more than 700% in patients added per year. SAD growth was greater than twice times comparing with PAD. By the end of the study 125 patients continued in follow up, 80% PAD y 20% SAD and 14 died.

Germline gain-of-function (GOF) mutation of the signal transducer and activator of transcription 3 (STAT3) gene causes a disease clinically characterized by a significant lymphoproliferation, including lymphadenopathy and/or hepatosplenomegaly, as well as childhood onset autoimmunity. Here we present an adult patient who, during his early years of life, presented recurrent infections, autoimmune hemolytic anemia and benign lymphoproliferative disease, characterized by hepatosplenomegaly and lymphadenopathy, being diagnosed with common variable immunodeficiency (CVID) at 13 years of age. He was diagnosed with lymphocytic interstitial pneumonia at the age of 20. When he was 40 years old, after a diagnostic review, it was decided to perform genetic studies. A heterozygous mutation in STAT3 NM&#95;003150 c.2141C>T, p.P714L was detected by whole exome sequencing and validated by Sanger. Previously published functional studies performed in two siblings showed that this mutation resulted in gain-of-function. They were initially diagnosed with autoimmune lymphoproliferative syndrome, and later with STAT3 GOF as a second genetic defect. Our patient developed severe pulmonary disease and died, without access to treatment targeted to his molecular defect due to the advanced nature of his pulmonary involvement and the fact that many of the therapies were still in development at that time. The diagnosis of STAT3 GOF mutations should be suspected in patients with early-onset of lymphoproliferative disease, autoimmunity and hypogammaglobulinemia. This must be considered especially in the group of CVID patients with these characteristics, in order to allow the implementation of treatments targeting the molecular defect (JAK inhibitors and Il-6 receptor antagonists) that could modify the disease evolution.

COVID-19, caused by SARS-CoV-2, emerged in late 2019 in Wuhan, China. Its clinical course is variable, as well as the mortality rate, which is higher among people over 65 years of age and persons with underlying conditions. Immunodeficiencies are potential risk factors for severe forms of COVID-19. Furthermore, patients with immunodeficiencies often undergo non-infectious complications, which could bear additional risk. So far, few reports of patients with COVID-19 and humoral immunodeficiencies have been published. Considering the importance of the study of this new viral disease and its potential health impact on patients with immunodeficiency disorders, we present six cases of COVID-19 in patients with impaired humoral immunity. Three were women and three were men. The average age was 48.5 years (range 20-67). Four had been diagnosed with primary antibody deficiency: three had common variable immunodeficiency and one had X-linked agammaglobulinemia. The other two patients had secondary hypogammaglobulinemia, one was associated with thymoma (Good's syndrome), and the other was associated with rituximab treatment. The evolution was favorable in all except the patient with Good's syndrome, who presented a marked decline in clinical status before contracting COVID-19.

Background: Common Variable Immunodeficiency (CVID) is characterized by an impaired antibody production and a higher susceptibility to encapsulated bacterial infections. Lung disease is considered to be the most important cause of morbidity and mortality., Methods: We analyzed clinical, radiological and functional characteristics in 80 patients with CVID assisted in the Unidad Inmunologia e Histocompatibilidad at Durand Hospital from 1982 to 2018., Results: Of the 80 patients, 55 showed pathologic lung Computed Tomography (CT). Twenty of them (36.4%) showed bronchiectasis; 26 (47.3%) interstitial involvement associated with nodules and adenopathies called GLILD (granulomatous-lymphocytic interstitial lung disease); and nine patients (16.3%) showed other lesions. Nine percent of patients with lung disease showed CT progression; none of them had spirometry worsening. GLILD patients had normal and restrictive patterns in lung function tests, in equal proportions. Two patients - one with GLILD and the other one with bronchiectasis - had an increase in spirometric pattern severity without CT progression. Lung biopsy was performed in 19% of GLILD patients, all of whom had histopathologic diagnosis of Lymphoid Interstitial Pneumonia (LIP)., Conclusions: GLILD is the major cause of lung disease in CVID. Computed tomography is useful for diagnosis but not necessary in follow-up, in which functional tests should have better correlation with clinical evolution, reducing radiation exposure. Biopsy should be indicated when the clinical diagnosis is unclear. Treatment should be considered whenever there is clear evidence of disease progression., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she developed chronic neutropenia. A bone marrow aspiration showed increased myeloid series with predominance of immature elements. On the basis of infections, low levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis of common variable immunodeficiency was made. She started intravenous immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts in hands that progressed to forearms, knees, abdomen and face were recorded. CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation, confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.

X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels and clinically by extracellular bacterial infections which mainly compromise the respiratory tract as well as recurrent diarrheas. The mainstay of treatment is gammaglobulin replacement therapy, which allows most patients to reach adulthood with high quality of life. We analyzed the clinical features of 14 patients over 18 years of age with XLA diagnosis that received treatment in our unit from the year 2003, the date the first patient was derived, until 2015. The average age at which patients were referred was 20.4 years old; age at the last consult was 25.5. The average follow-up time was 59.8 months. Previously to being diagnosed all patients had suffered infections, most frequently respiratory. After diagnosis all were started on intravenous gammaglobulin replacement treatment and in spite of infections being reduced in severity and frequency, there were cases of severe disease with long term sequelae. At the beginning of our follow-up 35.7% presented impaired respiratory function with only one case being severe. In no cases during this period did the respiratory function worsen, nor were there severe clinical complications. Three patients were switched to subcutaneous immunoglobulin treatment with good tolerance. The number of XLA cases is increasing, as most reach the second decade of life without serious complications and remain free of severe infectious disease and further impairment of their respiratory functions with the treatment.

Common variable immunodeficiency (CVID) is characterized by an impaired antibody production and an increased susceptibility to recurrent infections of the respiratory tract, mainly by extracellular encapsulated bacteria. We analyzed the clinical characteristics of 69 patients evaluated over a period of 10 years at three centers in the city of Buenos Aires. At the onset of the study 14 patients were on follow up, and at its end the number of patients reached to 60. Most of them consulted for infection or hypogammaglobulinemia and nearly half had an established diagnosis of immunodeficiency. Sixty-five (94.2%) patients had infections by encapsulated bacteria, four (6.1%) sepsis and two tuberculosis. The average age of onset of infectious symptoms was 18.1 years; the average age at diagnosis was 29.6 years and the delay to diagnosis 11.9 years. Forty one (59.4%) patients reported a history of recurrent or chronic diarrhea. In 22 (31.9%) 13 autoimmune diseases were diagnosed, being the most frequent the hematological disorders and hypothyroidism. Eight patients had histological polyclonal lymphoproliferation, four (5.8%) with granulomatous disease affecting the liver, the larynx and/or the skin; and four as lymphoid interstitial pneumonitis (LIP). Nineteen (27.5%) patients had splenomegaly and 23/57 (40.3%) images suggestive of lymphocytic or granulomatous processes (including the 4 with LIP) in the chest CT. Three (4.3%) patients developed B cell lymphoma, four (5.8%) stomach adenocarcinoma and one breast cancer. The study had a median follow-up of 54 months, range 1-353 and four patients (5.8%) died during the follow up.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, comprise a group of diseases characterized by inflammation of the wall of small vessels. We analyzed epidemiological and clinical characteristics in a series of 47 patients, 23 (49%) with Wegener granulomatosis (WG), 15 (32%) with microscopic polyangiitis (MPA) and nine (19%) with renal limited vasculitis (RLV). The mean age at onset of symptoms was 50.7 ± 14.9 years. The most frequent clinical manifestation was renal involvement in 41 (87%), followed by pulmonary manifestations in 26 (55%) and ENT involvement in 17 (36%). In 26 (55%) it presented with simultaneous pulmonary and renal involvement. The most frequent clinical category was the generalized form in 23 (49%), followed by the severe form in 18 (38%). Eighty nine percent of patients had positive ANCA test. Four (8%) received no immunosuppressive treatment. Of the 43 patients who were treated, 29 (67%) achieved complete remission with an average length of remission of 35.3 months. Eleven (26%) had a relapse, ten (91%) had a major relapse and one had a minor relapse. Twelve (28%) patients died, seven died early and five late during the course of the disease. Fifteen (31%) progressed to chronic renal failure. All 26 patients in follow-up had response to treatment and 20 (77%) were in remission at the end of the study. Despite the improvements achieved with immunosuppressive treatments, morbidity and mortality rates in ANCA-associated vasculitis remain high.

Antibody deficiency (AD) comprises a group of diseases characterized by the inability to develop an effective antibody mediated immune response. These patients suffer mainly of encapsulated extracellular bacterial infections of the respiratory tract. The aim of our study was to describe the clinical characteristics of 128 patients with suspected or confirmed AD who were referred to 3 immunodeficiency centers for adults, from June 2004 to December 2009. Three of these patients (2.3%) consulted for recurrent infections only once, without sufficient data for a proper classification, and were excluded. Of the remaining 125 patients, in 21 (16.8%) AD was excluded, 8 cases (6.4%) were diagnosed with secondary antibody immunodeficiency (SAD) and 96 (76.8%) with primary antibody immunodeficiency (PAD). SAD causes were: one renal failure, one phenytoin use, two monoclonal gammopathy and four B cell lymphoma. The causes of these 96 PAD were: 57 common variable immunodeficiency, 12 X-linked agammaglobulinaemia, 10 selective IgA deficiency, seven IgG1 deficiency, three hyper-IgM syndrome, three IgM deficiency, two X-linked proliferative syndrome, one Good syndrome and one antibody functional deficiency. Sixty-seven patients were in follow up at the time of completion of the study, 25 of them were on follow up at the beginning of the study. Among the 58 patients with indication of gamma globulin replacement therapy, 54 were in treatment at the end of the study. In four patients the initial diagnosis of PAD was not confirmed.