IgA Deficiency Research Articles

Selective IgA Deficiency and Aseptic Liver Abscess as Initial Indicators of Crohn’s Disease in a Young Woman: A Case Study

Selective IgA Deficiency and Aseptic Liver Abscess as Initial Indicators of Crohn’s Disease in a Young Woman: A Case Study

Eosinophilic pustular folliculitis associated with IgA deficiency

AbstractEosinophilic pustular folliculitis (EPF) is a noninfectious follicular based inflammatory dermatosis. We present a case of a 57‐year‐old female of Indian ethnicity who developed a pustular eruption, with certain lesions displaying Koebnerization. Given that the morphologic distribution most represented the immunosuppressant EPF subtype, additional testing led to the discovery of concurrent IgA deficiency. This case highlights a particularly unusual presentation of EPF associated with IgA deficiency and Koebner phenomenon.

The Latin American Society for Immunodeficiencies Registry.

Purpose - The Latin American Society of Immunodeficiencies (LASID) Registry was established in 2009 to collect data on Inborn Errors of Immunity (IEI) patients in the region. Although several reports have been published regarding LASID data, this is the first report of the entire dataset. Methods - The European Society of Immunodeficiencies (ESID) donated the online platform in 2008. Data was collected from participating centers from Apr 13, 2009, to Dec 31, 2022, and included demographic, clinical, and follow-up information. Results - A total of 9307 patients were included in the database. At the end of the study period, 8,805 patients were alive or lost to follow-up, and 502 were deceased. The most common type of IEI was predominantly antibody deficiency (PAD, 60.35%), and selective IgA deficiency was the most frequent diagnosis (1627 patients, 17.48%), followed by Common Variable Immune Deficiency (CVID, 1191 patients). Most patients (78.16%) were ≤ 18 years old at inclusion, and the median age at diagnosis was 4.77 years. The median time to diagnosis was 5.04 years. Antibiotics were prescribed in 32.3% of visits, followed by immunoglobulins (29.49% ). Hematopoietic stem cell transplantation was performed in 5.03% of patients. Omenn syndrome was the most common disease in deceased patients, with a mortality rate of 52.63%. Conclusion - This study contributes to our understanding of IEIs in Latin America and highlights the importance of early diagnosis, appropriate treatments, and improved data collection to optimize patient outcome.

Suppression of epithelial proliferation and tumourigenesis by immunoglobulin A.

Immunoglobulin A (IgA) is the most abundant antibody isotype produced across mammals and plays a specialized role in mucosal homeostasis 1 . Constantly secreted into the lumen of the intestine, IgA binds commensal microbiota to regulate their colonization and function 2,3 with unclear implications for health. IgA deficiency is common in humans but is difficult to study due to its complex aetiology and comorbidities 4-8 . Using genetically and environmentally controlled mice, here we show that IgA-deficient animals have increased susceptibility to endogenous colorectal tumours. Cellular and molecular analyses revealed that, in the absence of IgA, colonic epithelial cells induce antibacterial factors and accelerate cell cycling in response to the microbiota. Oral treatment with IgA was sufficient to both reduce steady-state proliferation and protect mice from tumours, but this function was due to antibody structure rather than binding specificity. In both organoid and monolayer culture systems, IgA directly suppressed epithelial growth. Co-immunoprecipitation mass spectrometry and a targeted CRISPR screen identified DMBT1 as an IgA-binding epithelial surface protein required for IgA-mediated suppression of proliferation. Together, IgA and DMBT1 regulate Notch signalling and tune the normal cycling of absorptive colonocyte progenitors. In mice, deleting the transmembrane and cytoplasmic signalling portions of DMBT1 or blocking Notch signalling was sufficient to reverse both the increased proliferation and tumour susceptibility of IgA knockouts. These experiments establish a homeostatic function for IgA in tempering physiological epithelial responses to microbiota to maintain mucosal health.

Increased Prevalence of Attention Deficit Hyperactivity Disorder in Individuals with Selective Immunoglobulin A Deficiency: A Nationwide Case-Control Study.

Background: Selective Immunoglobulin A Deficiency (SIgAD) is one of the most prevalent immunodeficiencies, characterized by an increased risk of mucosal infections. Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders and is associated with significantly higher rates of various infectious diseases, white blood cell abnormalities, and considerable morbidity. This study aimed to evaluate the prevalence of ADHD among patients with SIgAD. Methods: We conducted a retrospective, observational, population-based case-control study, within Leumit Health Services, by comparing individuals diagnosed with SIgAD to a matched control group. Data were extracted from electronic health records. Results: Of the >700,000 registered individuals, 772 aged ≥4 years with SIgAD were identified (mean age 22.0 ± 17.5 years; male/female ratio 1:1). The 5:1 matched control group consisted of 3860 subjects without SIgAD, with no significant differences between the groups regarding age, gender, ethnicity, and socioeconomic status. ADHD prevalence was significantly higher in the SIgAD group (16.2%) than in the control group (12.9%), with an odds ratio of 1.30 (95% confidence interval 1.05-1.61, p = 0.017), as was the use of methylphenidate (6.6% vs. 4%). Additionally, respiratory and intestinal infections were significantly more common in the SIgAD group (p < 0.001). Conclusion: A significantly higher prevalence of ADHD was observed in patients with SIgAD compared to strictly matched controls without SIgAD. These findings enhance our understanding of the pathophysiology of ADHD and its associated health complications.

High malignancy rate in IgE-deficient children.

Recent epidemiological studies have increasingly highlighted the antitumor efficacy of IgE owing to the increased malignancy rate in IgE-deficient patients. The purpose of this study, the largest for children, was to determine whether malignant diagnoses in children are associated with IgE deficiency (IgE <2.5 kIU/L). A total of 6821 pediatric patients were reviewed, focusing on patients with IgE below 2.5 kIU/L (n = 599). The causes of IgE testing were evaluated by categorizing them as having cancer, allergies, suspected or diagnosed immunodeficiency, and other conditions. In all but one patient with malignancy, IgE levels were measured after the diagnosis of the disease. Malignancies were observed much more frequently in the low IgE group than in the normal group (10/599, 1.7% and 7/6222, 0.11%; OR = 15.07; 95% CI: 5.72-39.75; p <.0001). According to our analysis, 70% of the patients had leukemia/lymphoma, which is consistent with studies showing that hematologic malignancies are the most frequent cancers linked to IgE deficiency. No increase in the prevalence of cancer was observed in IgE-deficient patients with suspected or diagnosed immunodeficiency. In conclusion, we observed a higher rate of previous malignancy (particularly hematologic cancer) in children with low serum IgE levels. Larger investigations would offer insightful information about the function of low IgE levels in predicting malignancy risk and improving the present diagnostic procedures.

7923 Latent Autoimmune Diabetes of Adulthood (LADA) Complicating Common Variable Immunodeficiency (CVID)

Abstract Disclosure: L. Pathak: None. M.G. Jakoby: None. Introduction: CVID is caused by defective B-lymphocyte maturation that results in immunoglobulin deficiency. Patients with CVID are predisposed to both infections and autoimmune disorders, with approximately 20% experiencing at least one autoimmune complication. We present a patient with LADA complicating CVID. Case A 31-year-old woman was referred for newly diagnosed diabetes mellitus (DM). Medical history was notable for primary hypothyroidism and apparent chronic lymphocytic thyroiditis. A presumptive diagnosis of type 2 DM was made due to obesity, and the patient was treated with metformin. However, she could not tolerate the medication due to diarrhea. Semaglutide was substituted and tolerated without adverse effects. During the first six months of treatment with semaglutide 0.5 mg weekly, HbA1c improved from 6.4 to 5.6%. However, in the next six months, HbA1c increased to 6.6% despite full compliance with medication and stable weight. Anti-glutamic acid decarboxylase (GADA) titer was unequivocally elevated at 69.8 IU/mL (0.0-5.0), though anti-insulin and islet antigen-2 (IA-2) antibodies were undetectable. Insulin glargine was added to the patient’s diabetes regimen, and HbA1c improved to 5.5% three months later. Discussion This patient meets Immunology of Diabetes Society diagnostic criteria for LADA, namely diabetes diagnosed in adulthood (≥ 30 y), elevated diabetes-associated autoantibody titer, and insulin independence for at least six months after diagnosis. Patients with high-titer GADA tend to be younger and have more rapid and significant loss of β-cell function than patients with low GADA titers, and this patient’s rapidly waning glycemic response to semaglutide conforms with this observation. Until recently, autoimmune diabetes in the setting of CVID was thought to be an unusual complication, though the prevalence of type 1 diabetes among CVID patients in the European Society for Immunodeficiency registry is 1.6%, approximately four-fold higher than the general European population. LADA shares genetic features linked to childhood-onset type 1 DM, making it possible or evenly likely that LADA has occurred in cases of CVID, though a careful search of PubMed failed to identify reported cases. This patient illustrates the importance of considering LADA in CVID, particularly with abrupt loss of glycemic response to noninsulin therapeutic agents. Presentation: 6/1/2024

B-052 Celiac Disease Risk Assessment of HLA-DQ Typing in IgA Deficient Patients

Abstract Background Celiac disease (CeD) is a chronic autoimmune disorder triggered by the ingestion of gluten in persons with the genetic risk factors human leukocyte antigens (HLA)-DQ2 and DQ8. Diagnostic evaluation of patients with suspected CeD often includes serology tests for tissue transglutaminase (tTG) antibodies. While the presence of HLA-DQ2 or DQ8 is required for the initiation and development of CeD, the genetic risk associated with the various alleles is not equivalent. Previous studies in patients with normal total IgA demonstrated the risk gradients of various HLA-DQ2 and DQ8 heterodimers in CeD. However, the impact of both gene variants in IgA deficient patients has not been investigated. In this study, HLA-DQ2 and HLA-DQ8 as risk factors for tTG-IgG positivity in IgA deficient patients were evaluated. Methods Retrospective data was collected from a cohort of individuals (n=3,515) with IgA concentrations below the age-dependent reference interval with suspicion for CeD who were tested for HLA-DQ genotyping and tTG-IgG (reference interval &amp;lt; 6 U/mL) at Mayo Clinic Laboratories. Total IgA was measured using quantitative nephelometry (Siemens BN™ II System); HLA typing was performed using the reverse SSO DNA typing assay (LABType SSO kits). tTG-IgG was determined by enzyme-linked immunosorbent assay (QUANTA Lite R h-tTG, Werfen Diagnostics) on the Dynex Agility System. The prevalence and frequency distribution of HLA-DQ2 and DQ8 haplotypes were determined and the odds ratio (OR) was calculated to evaluate the risk gradient for tTG-IgG positivity based on different HLA-DQ variants. Results Among IgA deficient patients, 58% (n=2,041) expressed HLA-DQ2 or DQ8 haplotypes. Relative to patients without permissive alleles, patients homozygous for HLA-DQ2.5 exhibited a significantly increased risk for tTG-IgG positivity (OR = 10.98, 95% CI: 6.56-18.18, p &amp;lt; 0.001) while those homozygous for HLA-DQ2.2 and DQ8 did not (DQ2.2/DQ2.2_OR = 0.72, 95% CI: 0.04-3.44, p = 0.75; DQ8/DQ8_OR = 0.96, 95% CI: 0.05-4.64, p = 0.97). Patients heterozygous for HLA-DQ2.5 (DQ2.5/x) displayed a lower odds ratio relative to homozygous patients (OR = 3.31, 95% CI: 2.29-4.82, p &amp;lt; 0.001); however, the risk for tTG-IgG positivity increased in the presence of HLA-DQ2.2 (DQ2.5/DQ2.2_OR = 7.59, 95% CI: 4.48-12.65, p &amp;lt; 0.001) or HLA-DQ8 (DQ2.5/DQ8_OR = 6.26, 95% CI: 3.55-10.73, p &amp;lt; 0.001) alleles. Conversely, in the absence of HLA-DQ2.5, HLA-DQ2.2 heterozygotes (DQ2.2/x_OR = 2.80, 95% CI: 1.77-4.39, p &amp;lt; 0.001) and HLA-DQ8 heterozygotes (DQ8/x_OR = 0.99, 95% CI: 0.52-1.77, p = 0.99) displayed lower correlations with tTG-IgG positivity, suggesting a potential risk elevation for tTG-IgG positivity is associated with the combination of DQ2.5 and DQ2.2 or DQ8. Conclusions Our study indicates the risk gradient of HLA-DQ genes in IgA deficient patients. Overall, compared to patients without HLA-DQ2 or DQ8 haplotypes, the homozygous HLA-DQ2.5 genotype had the highest correlation with tTG-IgG positivity, followed by HLA-DQ2.5/DQ2.2 and HLA-DQ2.5/DQ8 heterodimers. The results suggest that HLA-DQ2.2 or HLA-DQ8 alone does not confer risk, but when in the presence of HLA-DQ2.5 these alleles may increase the risk for tTG-IgG positivity. Results from this study shed light on the risk of CeD in patients with IgA deficiency.

Isotype deficiencies (IgG subclass and selective IgA, IgM, IgE deficiencies).

Background: Immunoglobulin G (IgG) subclass deficiencies and isolated IgA, IgM, IgE deficiencies have all been described in the literature with variable prevalence. Methods: These isotype deficiencies have a variable presentation from asymptomatic to recurrent infections resistant to prophylactic antibiotics. Results: Atopic disorders and autoimmune diseases are common comorbidities. IgE deficiency has been associated with impaired vaccine response and an increased risk of malignancy, particularly in patients with no allergic comorbidities and those with non-common variable immunodeficiency (CVID) humoral immunodeficiency, IgM deficiency, IgG2 deficiency, and CD4 lymphopenia. Conclusion: Close monitoring for malignancy should be strongly considered for these patients who are at risk. Treatment is variable and may include antimicrobial therapies for illnesses and prophylactic antibiotics in select patients, and immunoglobulin replacement can be considered for patients with refractory, recurrent infections.

P.249: Kidney transplantation in recipient with complete IgA deficiency.

P.249: Kidney transplantation in recipient with complete IgA deficiency.

Частота выявления и структура глютензависимых заболеваний среди гастроэнтерологических пациентов детского возраста Республики Узбекистан (когортное проспективное исследование)

Gluten-related disorders (GRDs) are characterized by different pathogenetic development pathways though are having similar clinical manifestations that make its differential diagnosis rather difficult. In the bibliographical sources available currently there were no research works such as a one-time study of the GRDs’ incidence among children. The purpose of this research was to determine the incidence and clinical and laboratory features of celiac disease (CeD), wheat allergy (WA) and non-celiac gluten sensitivity (NCGS) among children with gastroenterological complaints residing in Uzbekistan. Materials and methods used: a single-center cohort prospective study had been carried out in 2021-2022 on the basis of the Uzbekistan Republican Specialized Scientific and Practical Medical Center for Pediatrics of the Ministry of Healthcare of Uzbekistan (Tashkent, Uzbekistan) with 336 children with suspected gluten intolerance aged from 1 to 16 y/o who participated in the study. At the first stage 206 were selected after a short questionnaire developed by the Authors. For the following stage the specific laboratory tests were performed as follows: determination of antibodies (AT) to tissue transglutaminase IgA and total IgA (AT to tissue transglutaminase IgG, total IgG and IgM in IgA deficiency cases), total and specific IgE levels to wheat and gluten, HLA class II genotyping, histological examination of a biopsy specimen of the mucous membrane of the subbulbic part of the duodenum based on indications. The Salerno criteria were used to confirm the NCGS diagnosis. Results: the GRDs incidence among the studied cohort was 17.5% (95% CI: 12.29; 22.6), of which 5.3% (95% CI: 2.27; 8.41) had CeD, 7,3% (95% CI: 3.73; 10.83) had WA and 4.9% (95% CI: 1.92; 7.89) were diagnosed with NCGS. The most significant symptoms in children with GRDs were bloating, diarrhea and abdominal pain. The leading symptom for NCGS was headache. Allergic pinpoint rash with scratching traces were detected in patients with WA. Conclusion: this research was the first to study the GRDs incidence in Central Asia and it had showed that CeD and WA are pretty common among children with gastroenterological complaints in Uzbekistan and that the NCGS incidence does correspond to the average statistical data published priorly.

A small bowel adenocarcinoma harboring a DDR2 mutation in a celiac patient.

We present the case of a 62-year-old man with a history of celiac disease and IgA deficiency, following a strict gluten-free diet that was admitted to our hospital for recurrent abdominal pain, fatigue and melena. Esophagogastroduodenoscopy and colonoscopy with biopsies were normal. A video-capsule endoscopy was performed and revealed a sub-stenosing, vegetating, and bleeding lesion in the first jejunal loop. He underwent laparotomic surgery with resection of the involved segment with loco-regional lymphadenectomy. The pathological report described a poorly differentiated adenocarcinoma of the jejunum, stage IIIA (pT3pN1). Analysis of next-generation sequencing (NGS) of DNA on the surgical sample revealed a likely pathogenetic variant in exon 15 of the DDR2 gene (c.2003G > A) and a TP53 non-frame-shift deletion (c.585_602del). Considering the risk of recurrence, he was candidate to 6months of adjuvant chemotherapy with platinum salt and fluoropyrimidine. Thirty-eight months after the diagnosis, the patient is still disease free and in good clinical condition. This is the first described case of SBA with DDR2 mutation. Considering the limited therapeutic options beyond surgery for SBA, molecular analyses could become promising for the search for potential targetable alterations for treatments with new available drugs.

Laboratory Testing for Celiac Disease: Clinical and Methodological Considerations.

Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations. Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma. Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.

Immunoglobulin class-switch recombination: Mechanism, regulation, and related diseases.

Maturation of the secondary antibody repertoire requires class-switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high-affinity antibodies. Following immune response or infection within the body, activation of T cell-dependent and T cell-independent antigens triggers the activation of activation-induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper-IgM syndrome, Waldenström macroglobulinemia, hyper-IgD syndrome, selective IgA deficiency, hyper-IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.

IPINeT Ped-unPAD Study: Goals, Design, and Preliminary Results.

Background: An unclassified primary antibody deficiency (unPAD) is a widely heterogeneous clinical entity, recently identified within the spectrum of Inborn Errors of Immunity (IEIs). Since unPAD has been traditionally considered as a mild condition, it has incorrectly received little attention, resulting in the paucity of extensive and comparable studies describing its natural history. To address the gaps in characterizing, understanding, and managing pediatric unPAD patients, the Italian Primary Immunodeficiency Network (IPINet) Ped-unPAD study has recently been launched. Methods: Seventeen IPINeT Centers have expressed interest to participate, and data collection is still on-going. Hereby, we anticipate preliminary key issues emerging from the first 110 enrolled patients, attending three IPINet Centers. Results: A proportion of unPAD patients have experienced a severe infectious phenotype, which required hospitalization in a quarter of patients and antibiotic prophylaxis or Immunoglobulin Replacement Therapy in approximately 10% of patients. In this partial cohort, a mean follow-up (FU) of 5 years confirmed unPAD diagnosis in fifty percent of cases, with the remaining being reclassified as the Transient Hypogammaglobulinemia of Infancy (25%) and other IEIs (25%), such as a Common Variable Immunodeficiency, Selective IgA deficiency, Selective IgM deficiency, and IgG3 subclass deficiency. Conclusions: Despite a phenotype overlap at diagnosis, clinicians should be aware that unPAD is a mutable condition that deserves comprehensive evaluation and long-term monitoring to dissect the final diagnosis for optimal treatment.

Various clinical manifestations of 223 patients with IgE deficiency in a tertiary hospital in China: A cross-sectional study.

High Immunoglobulin E(IgE) levels associated with hypersensitivity or parasitic infection were well established, but the clinical significance of ultra-low IgE was largely unknown. Previous studies indicated these patients have an elevated risk of cancer, but large-scale epidemiological studies on the prevalence and clinical manifestations of these ultra-low IgE patients are still lacking. A total of 62,997 patients who were admitted to the First Affiliated Hospital of Wenzhou Medical University and had IgE level tests from January 2010 to March 2020 were included. Patients with serum IgE levels < 2 IU/mL were defined to have ultra-low IgE. And the clinical characteristics of these patients were retrospectively analyzed based on electronic medical record system and follow-up. A total of 223 patients (223/62,997, 0.35%) had ultra-low IgE were documented in 62,997 patients who had IgE tests. Among the clinical manifestations of these 223 ultra-low IgE patients, infection ranked first (125/223, 56.05%), following allergic diseases (51/223, 22.87%), hematological disorders (37/223, 16.59%), tumor (27/223, 12.11%) and autoimmune diseases (23/223, 10.31%). To the best of our knowledge, we first reported that the prevalence and clinical characteristics of 223 ultra-low IgE patients in China. The most common comorbidities were infection, allergic diseases, hematological disorders, tumor and autoimmune diseases.

An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression

Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.

Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0) and5.0 (3.0-8.0)years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Temporal patterns of IgE levels in patients with IgE deficiency

Temporal patterns of IgE levels in patients with IgE deficiency

Immunological Evaluation of Pediatric Patients with Polyautoimmunity.

Autoimmunity can be the first or predominant manifestation in patients with primary immunodeficiency disorder, also referred to as inborn errors of immunity (IEI). This study aims to evaluate the immune status of pediatric patients with polyautoimmunity to identify those with underlying immune defects. In this cross-sectional study, pediatric patients with polyautoimmunity including at least one confirmed autoimmune endocrine disease were enrolled. Demographic and clinical data were collected using a questionnaire based on medical records and direct family interviews. For each patient, a basic immunologic evaluation was performed. The clinical diagnosis was established according to the criteria of the European Society for Immunodeficiencies (ESID). Based on the presence or absence of a history of severe and/or recurrent infections, patients were divided into two groups for comparison. Thirty-nine patients, 18 males (46.2%) and 21 females (53.8%), were included. Fourteen patients (35.9%) had consanguineous parents. Fifteen patients (38.5%) had a history of severe and/or recurrent infections. The median (interquartile range: IQR) age of our patients at the time of evaluation was 11.1 (9-16) years. The median (IQR) age at the onset of infections and autoimmunities were 3 (1-10.8) and 5 (2.6-8) years, respectively. The most common infectious complications reported were pneumonia and candidiasis, each in 12.8% of the patients. The most prevalent autoimmune disorders were type 1 diabetes (74.3%) and autoimmune thyroiditis (58.9%). IEI was diagnosed in six patients (15.38%), five of which were from the group with severe or recurrent infections: three with selective IgA deficiency, two with common variable immunodeficiency (CVID), and one with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX), but without a history of infections. The occurrence of early onset polyautoimmunity in association with severe and/or recurrent infections or in patients with a positive family history should be a warning sign for physicians to initiate an evaluation for possible immunodeficiency disorders to prevent complications through early treatment.