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G6PC3 deficiency is a monogenic immunometabolic disorder that causes syndromic congenital neutropenia. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Here, we investigated the origin and functional consequence of the G6PC3 c.210delC variant found in patients of Mexican origin. Based on the shared haplotypes amongst carriers of the c.210delC mutation, we estimated that this variant originated from a founder effect in a common ancestor. Furthermore, by ancestry analysis, we concluded that it originated in the indigenous Mexican population. At the protein level, we showed that this frameshift mutation leads to an aberrant protein expression in overexpression and patient-derived cells. G6PC3 pathology is driven by the intracellular accumulation of the metabolite 1,5-anhydroglucitol-6-phosphate (1,5-AG6P) that inhibits glycolysis. We characterized how the variant c.210delC impacts glycolysis by performing extracellular flux assays on patient-derived cells. When treated with 1,5-anhydroglucitol (1,5-AG), the precursor to 1,5-AG6P, patient-derived cells exhibited markedly reduced engagement of glycolysis. Finally, we compared the clinical presentation of patients with the mutation c.210delC and all other G6PC3 deficient patients reported in the literature to date, and we found that c.210delC carriers display all prominent clinical features observed in prior G6PC3 deficient patients. In conclusion, G6PC3 c.210delC is a loss-of-function mutation that arose from a founder effect in the indigenous Mexican population. These findings may facilitate the diagnosis of additional patients in this geographical area. Moreover, the in vitro 1,5-AG-dependent functional assay used in our study could be employed to assess the pathogenicity of additional G6PC3 variants., Competing Interests: Competing Interests The authors declare that they have no relevant conflicts of interest. Additional Declarations: No competing interests reported.

Background: SARS-CoV-2 infection associated with the presence of comorbidities increased the risk of mortality. However, the role of asthma as a predictor of mortality and severity has not been defined., Aim: To assess the impact of asthma as a factor associated with the decrease in mortality in the Mexican population with COVID-19., Methodology: We performed a cross-sectional and secondary analysis of the database of the General Directorate of Epidemiology of the Mexican Government, updated to May 2023. The analysis included the Mexican population with a confirmed diagnosis of SARS-CoV-2 by RT-PCR., Results: A total of 617,367 participants were included, with a mean age of 36. Mortality was 0.9%, 0.2% required admission to the intensive care unit (ICU). The prevalence of asthma in this population was 1.9%. When performing the multivariate logistic regression analysis, we found that the presence of asthma decreased the risk of mortality, with an OR of 0.57 (95% CI 0.45, 0.72; p = < 0.001). The variables of age > 60 years, smoking, arterial hypertension, Diabetes, Chronic Obstructive Pulmonary Disease (COPD), cardiovascular disease, and chronic kidney disease (CKD) were factors associated with an increase in mortality. The diagnosis of asthma was not associated with mechanical ventilation or ICU admission., Conclusion: The presence of asthma in patients with COVID-19 decreased the risk of mortality by 43%. The immunological context could explain the decreased risk of mortality in asthmatic patients infected with SARS-CoV-2.

Introduction: Up to 25% of patients with common variable immunodeficiency (CVID) debut with autoimmunity, which is related to the Freiburg classification, which is based on flow cytometry., Objective: to determine the frequency and type of autoimmune diseases and their association with the Freiburg classification in adults with CVID., Methods: A cross-sectional, analytical and observational study was carried out with 33 patients belonging to the Primary Immunodeficiency Clinic of a third level hospital, with a diagnosis of CVID. They were divided into 3 phenotypes according to the Freiburg classification., Results: Of the 33 patients studied, 66.6% presented autoimmune diseases, 19 of them (86.3%) had cytopenia; 42.1% belonged to Freiburg group Ia, 36.8% to Ib and 21% to phenotype II. In 36.6% of the patients, autoimmune cytopenia were the first manifestation of CVID; and up to 70% of them belong to the Freiburg phenotype Ia (p = 0.086). Patients with autoimmune cytopenia had a lower percentage of isotype-switched memory B cells (p = 0.018), no higher percentage of CD21low B cells (p = 0.226)., Conclusions: Classification by CVID phenotypes allows the identification of the patient's profile according to the percentage of memory B cells with isotype change, which is useful to intentionally search for non-infectious complications of the disease., (Licencia CC 4.0 (BY-NC-ND) © 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Pollen-food syndrome (PFS) is characterized by allergic sensitization to proteins of pollens of grasses, weeds, and trees, which produce a type I hypersensitivity reaction that is associated with the intake of plant-derived foods that are usually in raw form. The most frequently-associated protein families are: profilins, PR-10, and ns LTP; however, others such as thaumatins, isoflavones, reductases, and B1,2 glucanases have been documented. The prototype syndrome is birch-fruit-vegetables, and of these, the most common is birch-apple due to the fact that more than 70 % of patients who are sensitized to birch present symptoms associated with the intake of plant-derived foods. The symptoms are restricted to the oral cavity; however, some patients may present systemic symptoms, including anaphylaxis, so it is important to identify the type of protein that is involved since the type of reaction that the patient may present depends on that. In spite of everything, it is considered an entity that may be under diagnosed due to its complex diagnosis and treatment, since the procedure, in most cases, is an elimination diet, because treatment with immunotherapy is not yet available. The purpose of this review is to describe the pathophysiology, as well as the most common pollen-food syndromes.

Background: The SARS-CoV-2 disease, called COVID-19, emerged in China has acquired pandemic dimensions. According to the WHO situational report of March 15, 2021, the global fatality rate is 2.2%; in Mexico, around 194 944 deaths have been confirmed by COVID-19. Studies in China identified that patients with severe COVID-19, when compared with those who had non-severe COVID-19, presented more severe neurological manifestations., Objective: To determine the frequency of neurological symptoms and manifestations in patients with severe COVID-19 in a tertiary care center., Material and Methods: A cross-sectional, observational and analytical study was carried out at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, in patients hospitalized with severe COVID-19., Results: 183 cases were analyzed, of which 130 were men (71%). The median age was 55 years (IQR: 44-65). The neurological symptoms were: headache, anosmia and dysgeusia. Neurological manifestations occurred in 27 patients (16%), the most frequent was ischemic-type cerebrovascular disease (CVD) in 12 (44%), in patients older than 76.5 years vs. 54 years (p = 0.000), with history of cardiovascular disease., Conclusions: The most frequent neurological symptoms were headache, anosmia and dysgeusia. The most frequent neurological manifestation was ischemic CVD that appeared in older patients with severe COVID-19 with a history of cardiovascular disease., (© 2021 Instituto Mexicano del Seguro Social.)

Background: Chronic urticaria (CU) affects 5 % of the general population and it is associated with thyroid disease in up to 54 % of patients. There is scarce information on the activity of urticaria in patients with and without alterations in the thyroid function., Objective: To compare the activity rate of urticaria using the UAS7 (Urticaria Activity Score 7) in patients with and without hypothyroidism., Methods: A descriptive, cross-sectional, and comparative study of patients with CSU (chronic spontaneous urticaria) who were older than 18 years of age, who were classified into two groups based on their thyroid function: hypothyroid and euthyroid patients. UAS7 was applied to all of them., Results: We analyzed 60 patients with CSU; 30 of them were euthyroid and 30 were hypothyroid. The female sex was predominant (76 %) and the average age was 49.1 years old. The activity in 40 % was moderate, in 25 % was severe, and it was mild in 23 %; only 12 % of them were controlled. In the group with hypothyroidism, the median TSH (Thyroid Stimulating Hormone) was of 6.8 μUI/mL. No statistically significant differences were found in matters of age, body mass index, comorbidities, or in the UAS7., Conclusions: We did not find a statistically significant difference in the Urticaria Activity Index between both groups. Identifying the influencing factors shall improve the quality of life of patients.

Background: There is limited epidemiological information on the treatment of atopic dermatitis (AD) from specialist physicians in Mexico., Objective: To know the criteria that is used by specialists in Mexico to diagnose and treat AD., Methods: An observational, descriptive and cross-sectional study, which was authorized by the ethics committee, was carried out through an electronic survey., Results: 114 surveys were carried out; 56% of the participants were allergists, 38% were dermatologists and 5% were pediatricians. It was identified that 54% used clinical criteria for the diagnosis of AD and 42% used the criteria of Hanifin-Rajka as a diagnostic complement; 38% requested total and/or specific IgE, blood biometry and blood chemistry tests. They recount that 90% of patients under the age of 18 had mild AD, 8% had moderate AD and 2% had severe AD; and, in patients over the age of 18, 89% had mild AD, 6% had moderate AD and 5% had severe AD. The patients' care was multidisciplinary, since 57% of the survey respondents requested assessments combined with ophthalmology, dermatology and allergology., Conclusion: Knowledge of the disease will lead to a better control of the disease. The challenge is to have a patient registry, update treatment guidelines, consider comorbidities and have therapeutic options for its control.

Background: Common variable immunodeficiency (CVID) is the most common primary symptomatic humoral immunodeficiency in adults. Antibody deficiency entails higher susceptibility to sinopulmonary infections and bronchiectasis formation, which is related to increased mortality. Scales have been established to assess the degree of severity of bronchiectasis in order to predict outcomes such as mortality, exacerbations and hospitalizations., Objective: To determine bronchiectasis severity in adult patients with common variable immunodeficiency using the Brief Symptom Inventory scale., Method: Cross-sectional study in adult population diagnosed with common variable immunodeficiency and attended to at the Mexican Institute of Social Security National Medical Center Siglo XXI Specialty Hospital., Results: Bronchiectasis severity according to the Brief Symptom Inventory was mild in 60% of patients and moderate in 40%. Statistically significant differences were found for body mass index, number of affected lobes and type of bronchiectasis (p < 0.001)., Conclusions: Using bronchiectasis severity scales in patients with common variable immunodeficiency is indispensable for clinical and therapeutic decision making; however, determining the most appropriate instrument to assess bronchiectasis severity in this population is necessary.

Background: Latex-fruit syndrome (LFS) is characterized by allergy to latex and plants. Papain, chymopapain, caricaine and class I chitinases are papaya's most allergenic proteins. The similarity between latex hevein epitopes and papaya class I chitinases might explain the latex-papaya syndrome (LPS)., Objective: To describe the clinical characteristics of patients with LPS., Methods: Cross-sectional, observational, descriptive study where 11 patients diagnosed with latex allergy by skin prick test and clinically diagnosed with papaya-induced anaphylaxis were included. The results were analyzed with descriptive statistics., Results: Out of 11 patients with LPS, 72.7% were females (7 to 46 years), all with a history of papaya-induced anaphylaxis, identified by medical history and medical notes plus latex-positive skin prick tests, with 63.3% exhibiting anaphylaxis in the skin prick tests. Risk factors included multiple surgeries, another allergic disease, and being employed in the field of health; 63.6% were allergic to to other foods, 45.4% to medications, 45.4% had allergic rhinitis and 27.3% had asthma., Conclusions: Hypersensitivity to papaya increases the risk of anaphylaxis in patients with latex allergy and, therefore, mortality. Clinical data is the main diagnostic tool. Education for the management of anaphylaxis with adrenaline self-administration is essential.

Multiple sclerosis is a demyelinating inflammatory disease that affects the central nervous system. Its etiology is the result of a complex interaction between genetic and environmental factors that trigger a deregulated immune response, with the resulting inflammation and neuronal/axonal degeneration. Neuroinflammation is triggered when peripheral leukocytes migrate to the central nervous system and release cytokines such as interleukins 1 and 6 (IL-1 and 6) and tumor necrosis factor (TNF), which act on dwelling cells. The innate immune system plays an important role in the onset and progression of the disease by identifying molecular patterns associated with pathogens and damage, which modulate effector and regulatory functions of the cells where they are expressed, in order to direct the specific immune response. Th17 cells favor the disruption of the blood-brain barrier, which enables the migration of leukocytes to the central nervous system and the triggering of the inflammatory cascade; the Th1 profile (IL-1, IL-6) collaborates to perpetuate it. B-cell function is to produce antibodies and cytokines (IL-6, IL-12 and TFN). Knowledge on multiple sclerosis pathophysiology will enable the development of new therapeutic options that impact on natural history of the disease and its prognosis., (Copyright: © 2018 SecretarÍa de Salud.)

Primary immunodeficiencies (PIDs) are low-incidence diseases caused by defects in genes involved in the development, maintenance, and regulation of the immune system. Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency of adulthood. It has an approximate prevalence of 1 in 25 000-50 000 in the general population, with a delay in diagnosis between 6-7 years. The clinical manifestations of CVID constitute six main categories: infections, pulmonary complications, granulomatous or polyclonal lymphocytic disease, autoimmunity, gastrointestinal diseases and malignancy Most patients must have at least one of the following clinical manifestations (infection, autoimmunity, lymphoproliferation). However, the diagnosis of CVID can be conferred in asymptomatic patients, especially in familial cases. Secondary causes of hypogammaglobulinemia should be ruled out in any patient meeting the diagnostic criteria for CVID, as the treatment may be totally different from that required for CVID. Because CVID comprises a heterogeneous group of syndromes with poor primary antibody production, the potential number of entities within this group is unknown. Patients with CVID suffer from various complications that are considered prognostic. In the absence of clear guidelines for their search, it is recommended that lymphoproliferative disease, lung disease, liver disease and autoimmunity be investigated intentionally during the initial evaluation. The intervals in which they should be performed are not clear, but several evaluations may be required per year, according to the clinical evolution of the patient.

Background: Good's syndrome is an association of thymoma and immunodeficiency. The symptoms are recurrent sinopulmonary infections in addition to the compressive side of thymoma. A laboratory finding is notable for the absence or decrease of B lymphocytes, hypogammaglobulinemia, inversion ratio CD4/CD8 and abnormal proliferative response to mitogens., Case Report: Female, 49-year-old started five months earlier with lower limb edema, postprandial vomiting, dysphagia, chronic diarrhea and weight loss. A second endoscopy ruled gastric neoplasia. Chest radiography with mediastinal widening, Thoraco-abdominal CT with bilateral pleural effusion and a mass in the anterior mediastinum, histopathological report of the tumor: B1 thymoma. Laboratory findings: IgG 349 mg/dL, IgA 70.3 mg/dL, 37.1 IgM mg/dL, Ca125 631 UI/mL, leukocytes 7890 mm3, hemoglobin 13.2 g/dL, lymphocytes 2060 mm3, CD16+CD56+ 122 cells/µL, CD19 77 cells/µL, CD3 2052 cells/µL, CD4 977 cells/µL, CD8 998 cells/µL; ratio CD4/CD8 0.98, hepatitis C, B and HIV negative. They requested valuation to Clinical Immunology and Allergy due to hypogammaglobulinemia, the diagnosis of Good's syndrome was confirmed and initiated with intravenous gamma globulin replacement to immunomodulatory dose of 1 g/kg, she reached replacement goal in the third dose of immunoglobulin intravenous, with clinical improvement. She died four months later from cardiac complications., Conclusions: Despite the variability of presentation, Good's syndrome should be suspected as part of the paraneoplastic manifestations of thymoma.

Background: Bronchiectasis are permanent dilatations of the bronchi. Its prevalence in patients with variable common immunodeficiency (CVID) is high, however there is little information regarding the type and location of the same; therefore the objective of this study is to know the type and location of bronchiectasis in a cohort of adult patients with CVID., Methods: It has been made a transversal, observational and descriptive study that included 32 adult patients with diagnosis of CVID according to the criteria of the European Society of Immunodeficiencies (ESID). All patients underwent high resolution pulmonary computed tomography (HRCT), which were interpreted by an expert radiologist. The frequency, type and location of bronchiectasis were reported using descriptive statistics., Results: Thirty-two adult patients, ten men (31.25%) and 22 women (68.7%), were included. 40.6% had bronchiectasis. 23% had a lobe involvement, 15.3% two lobes, 46.1% 3 lobes and 15.3% complete involvement of the parenchyma. The types of bronchiectasis were distributed as follows: tubular 38.4%, varicose 23% and cystic and tubular combinations 15.3%, cystic and varicose 15.3% and cystic, tubular and varicose 7.6%., Conclusions: Our results show that 40% of adult patients with CVID have BQs, usually affecting three pulmonary lobes, located mainly in the right and middle lower lobe; The tubular type, is the most common. Their timely diagnosis and treatment can improve survival and reduce costs for patients and health care.

Background: Patients with common variable immunodeficiency show higher incidence of sinopulmonary and gastrointestinal infections, as well as lymphoproliferative and autoimmune diseases. The treatment of choice is replacement therapy with human gamma-globulin. Hematopoietic stem cell transplantation is a non-conventional therapeutic modality., Case Report: Twenty-six-year old woman with no family or hereditary history of primary immune deficiencies or consanguinity, with repeated episodes of otitis, sinusitis, gastroenteritis and bronchitis since childhood. At adolescence, she was diagnosed with common variable immunodeficiency; she was prescribed intravenous gamma-globulin, broad-spectrum antimicrobials and macrolides. At 22 years of age, she underwent hematopoietic stem cell transplantation owing to continued severe infections. At 4 months, post-transplantation she was diagnosed with hypothyroidism and ovarian insufficiency. During the following 3 years, she had no infections, but at 25 years of age she had immune thrombocytopenic purpura diagnosed, which persists together with Raynaud's disease and upper respiratory tract persistent infections. At the moment of this report she is being treated with intravenous gamma-globulin and receiving prophylaxis with clarithromycin, without steroids or danazol., Conclusions: Given the high rate of morbidity and mortality associated and immune reconstitution failure, hematopoietic stem cell transplantation should be carefully evaluated in patients with treatment-unresponsive infections or lymphoproliferative disorders.

Background: Primary immunodeficiencies (PID) are characterized by alteration of the components of the immune system. Humoral deficiencies represent 50%. The most common are selective IgA deficiency, Bruton agammaglobulinemia, and common variable immunodeficiency (CVID)., Objective: To describe the epidemiological and clinical characteristics of adults with humoral PID, cared for in a Primary Humoral Immunodeficiencies Clinic., Methods: A descriptive cross-sectional study that included a year of analysis, including 35 patients with humoral PID, 31 with CVID, and 4 with Bruton agammaglobulinemia. Data were analyzed with descriptive statistics., Results: Of 35 patients studied, 31 had CVID (88.5%) and 4 (11.5%) Bruton agammaglobulinemia; 21 were men and 14 women. The age at onset of symptoms was 22.7 years, and the delay in diagnosis was 7.2 years. 11.4% of CVID patients died during the study; 4 had malignancies, 22.8% autoimmune diseases, and 48.5% gastrointestinal disorders. Patients with Bruton agammaglobulinemia presented no comorbidities., Conclusions: Unlike reports in the literature, in the study group, CVID was the most common cause of humoral PID, predominantly in men; the most common gastrointestinal disorder was intestinal functional disorder.

Background: The prevalence of chronic rhinosinusitis in adult patients with common variable immunodeficiency (CVID) is 52%. The patients with CVID show higher incidence of chronic rhinosinusitis, which is an inflammatory disease that affects the lining of one or more paranasal sinuses and nasal cavity., Objective: To identify the microorganisms in the middle meatus secretion obtained by endoscopy associated with chronic rhinosinusitis in adult patients with common variable immunodeficiency (CVID)., Material and Method: A descriptive, cross-sectional study, which included adult patients with CVID, from whom a sample endoscopic middle meatus secretion from both nostrils was obtained and sent to culture for aerobic, anaerobic bacteria and fungi. Informed consent of all patients was obtained., Results: 29 patients were studied: 18 women and 11 men with a mean age of 40±13 years. The results were: 2 samples showed no microbial growth, 24 showed growth of aerobic bacteria, 3 cases had fungal growth without development of anaerobic bacteria., Conclusions: Our results show that the most common microorganisms associated with CSR in adult patients are: Moraxella catarrhalis, Staphylococcus, Sphingomonas paucimobilis and Citrobacter koseri, and associated fungal agents were: Candida albicans and Aspergillus fumigatus.

Background: Systemic lupus erythematous is an autoimmune disease of multifactorial etiology with genetic predisposition. Its pathogenesis involved more than 100 genes. CD24 gene can mediate various functions such as their costimulatory activity in the clonal expansion of T cells. The single nucleotide polymorphism, resulting in a non-conservative replacement of alanine to valine (CD24v) precedes immediately GPI anchorage site (position ω-1), determines CD24 loss activity. CD24v has been associated with multiple sclerosis and systemic lupus erythematous in other populations., Objective: To find the presence of CD24v in Mexican patients with systemic lupus erythematous., Material and Method: A study of fenotyping of CD24v included 65 subjects, 32 cases (systemic lupus erythematous): 28 women and 4 men; and 32 controls: 9 women and 23 men; cases and controls from patients with systemic lupus erythematous in National Medical Center 20 de Noviembre ISSSTE, Mexico City, services of Clinical Immunology and Rheumatology., Results: In cases, 19 patients had a wild homozygous genotype, 12 were heterozygous and only one patient showed homozygous polymorphism. In controls, 17 showed wild heterozygous genotypes; 14 were heterozygous and 1 was found to be polymorphic homozygote. With odds ratio: 0.84 and chi-squared of 0.17; therefore there was no statistically significant difference., Conclusions: Study population showed that there is no statistically significant difference between systemic lupus erythematous cases and controls with respect to the presence of CD24v.

Common variable immunodeficiency (CVID) is an heterogeneous group of disorders characterized by impaired antibody production. It shows a wide spectrum of manifestations including severe and recurrent respiratory infections (Streptococcus pneumoniae, Haemophilus) and gastrointestinal (Campylobacter jejuni, rotavirus and Giardia lamblia). Viral infections caused by herpes zoster, cytomegalovirus (CMV) and hepatitis C are rare. The opportunistic agents such as CMV, Pneumocystis jirovecii, cryptococcus and atypical mycobacteria have been reported as isolated cases. This paper reports the case of a 38-year-old female patient, who began six years before with weight loss of 7 kg in six months, fatigue, weakness, sweating, fever and abdominal pain. Furthermore, patient had intestinal obstruction and abdominal CT showed mesenteric lymph growth. The mesenteric lymph node biopsy revealed positives Mycobacterium PCR, Ziehl-Neelsen staining and culture for M. bovis. In the laparotomy postoperative period was complicated with nosocomial pneumonia, requiring mechanical ventilation and tracheostomy. Two years later, she developed right renal abscess that required surgical drainage, once again with a positive culture for Mycobacterium bovis. She was referred to highly specialized hospital and we documented panhypogammaglobulinemia and lymphopenia. Secondary causes of hypogammaglobulinemia were ruled out and common variable immunodeficiency (CVID) was confirmed, we started IVIG replacement. Four years later she developed mixed cellularity Hodgkin's lymphoma. Until today she continues with IVIG and chemotherapy. This report of a patient with CVID and Mycobacterium bovis infection, a unusual association, shows the cellular immunity susceptibility in this immunodeficiency, additional to the humoral defect.