A portable surface plasmon resonance (SPR) sensor for the detection of immunoglobulin A in plasma.

BACKGROUND: A life-threatening anaphylactic shock can occur if a patient with undiagnosed immunoglobulin A (IgA) deficiency (i.e., IgA levels <500 ng/mL) receives IgA-containing blood, hence the need for a rapid, point-of-care (POC) method for IgA deficiency screening. Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect IgA, but this method requires trained specialists and ≥24 h to obtain a result. We developed a surface plasmon resonance (SPR)-based protocol to identify IgA-deficient patients or donors within 1 h. MATERIALS AND METHODS: The SPR sensor relies on the detection of IgAs captured by primary antibodies adsorbed on the SPR chip and quantified with secondary antibodies. The sensor was calibrated from 0 to 2000 ng/mL in buffer, IgA-depleted human serum, and plasma samples from IgA-deficient individuals. A critical concentration of 500 ng/mL was set for IgA deficiency. The optimized sensor was then tested on eight plasma samples with known IgA status (determined by ELISA), including five with IgA deficiency and three with normal IgA levels. RESULTS: The limit of detection was estimated at 30 ng/mL in buffer and 400 ng/mL in diluted plasma. The results obtained fully agreed with ELISA among the eight plasma samples tested. The protocol distinguished IgA-deficient from normal samples, even for samples with an IgA concentration closer to critical concentration. DISCUSSION: In conclusion, we developed a reliable POC assay for the quantification of IgA in plasma. This test may permit POC testing at blood drives and centralized centers to maintain reserves of IgA-deficient blood and in-hospital testing of blood recipients.

Intestinal Candida albicans overgrowth in IgA deficiency.

BACKGROUND: Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, whether human IgA-deficiency is associated with gut fungal dysbiosis remains unknown. OBJECTIVES: Our goal was to study the impact of IgA on gut mycobiota ecology. METHODS: The Fungi-Flow method was used to characterize fecal, systemic, and maternal IgA, IgM, and IgG responses against 14 representative fungal strains (yeast/spores or hyphae forms) in healthy donors (HDs) (n = 34, 31, and 20, respectively) and to also compare gut mycobiota opsonization by secretory antibodies in HDs (n = 28) and patients with selective IgA deficiency (SIgAd) (n = 12). Stool mycobiota composition was determined by internal transcribed spacer gene sequencing in HDs (n = 23) and patients with SIgAd (n = 17). Circulating CD4+ T-cell cytokine secretion profiles were determined by intracellular staining. The impact of secretory IgA, purified from breast milk (n = 9), on Candidaalbicans growth and intestinal Caco-2 cell invasion was tested in vitro. RESULTS: Homeostatic IgA binds commensal fungi with a body fluid-selective pattern of recognition. In patients with SIgAd, fungal gut ecology is preserved by compensatory IgM binding to commensal fungi. Gut Calbicans overgrowth nevertheless occurs in this condition but only in clinically symptomatic patients with decreased TH17/TH22 T-cell responses. Indeed, secretory IgA can reduce in vitro budding and invasion of intestinal cells by Calbicans and therefore exert control on this pathobiont. CONCLUSION: IgA has a selective impact on Calbicans ecology to preserve fungal-host mutualism.

Prevalence of neurological diseases among patients with selective IgA deficiency.

Background: There are no published epidemiologic studies with regard to the prevalence of neurologic diseases among subjects with selective immunoglobulin A (IgA) deficiency (sIgAD). Objective: To investigate the prevalence of neurologic diseases among the Israeli population with sIgAD. Methods: A population-based case-control study among members of a large nationwide health maintenance organization in Israel providing services to > 700,000 members. The sIgAD group included individuals ≥4 years of age with a serum IgA level of <0.07 g/L and with a diagnosis of sIgAD. The control group was randomly sampled from the entire study population with a case-control ratio of five controls for each case (1:5), with exact matching for age, gender, ethnic group, and socioeconomic status category. Results: A total of 796 subjects ages 20.58 ± 15.46 years; 391 female subjects (49.1%) were identified as having sIgAD. The control group was constituted of 3980 matched subjects. The sIgAD group was characterized by a higher prevalence of autism spectrum disorder and tic disorders. Migraine was less prevalent in the sIgAD group (19 [2.39%]) than in the control group (168 [4.22%]), odds ratio (OR) 0.55 (95% confidence interval {CI}, 0.34-0.90); p = 0.016]. More cases of subjects with epilepsy were observed in the sIgAD group (14 [1.76%]) than in the control group (31 [0.80%]), OR 2.28 (95% CI, 1.12 - 4.44; p = 0.015). Conclusion: Our observation raises the question of the role of IgA in noninfectious diseases of the central nervous system. Further basic studies are needed to explain our observation.

[Acute Aortic Dissection Complicated by IgA Deficiency].

Immunoglobulin A (IgA) deficiency is the most common type of primary immunodeficiency. When a patient receives a blood product transfusion, anti-IgA antibodies are formed. Second transfusion may sometimes cause an anaphylactic reaction, thus caution is necessary. Reported here is a case of Stanford type A acute aortic dissection performed in the patient with IgA deficiency with a history of blood transfusion. Red blood cells and platelet were washed and prepared, and flesh frozen plasma from IgA deficient donors was obtained. Thereafter, the surgery was safely performed.

Pediatric Celiac Disease and Selective IgA Deficiency: Unexpected Sequence of Events.

PURPOSE: Selective IgA deficiency (IgAD) is the most common primary immunodeficiency, frequently leading to only minor clinical complaints. IgAD may be associated with autoimmune diseases such as celiac disease (CeD). Although IgAD is thought to precede CeD and autoimmunity, the association between the two conditions has not been clarified. METHODS: Routine techniques were used to measure serum IgA and celiac diagnostic markers as transglutaminase 2 IgA (TG2-IgA) and deamidated gliadin IgG and for immunohistochemistry for IgG, IgM, and IgA. RESULTS: We report two childhood cases of complete IgA deficiency that evolved after the diagnosis of CeD and the start of a gluten-free diet. Histology showed persistence of IgA in the intestinal mucosa. CONCLUSION: Both children with CeD showed IgA deficiency that unexpectedly developed after the initiation of a gluten-free diet. This supports IgA deficiency as a process that develops gradually and occurs due to specific defects in immunoregulation.

Gut Microbiota Perturbation in IgA Deficiency Is Influenced by IgA-Autoantibody Status.

BACKGROUND & AIMS: IgA exerts its primary function at mucosal surfaces, where it binds microbial antigens to regulate bacterial growth and epithelial attachment. One third of individuals with IgA deficiency (IgAD) suffers from recurrent mucosal infections, possibly related to an altered microbiota. We aimed to delineate the impact of IgAD and the IgA-autoantibody status on the composition and functional capacity of the gut microbiota. METHODS: We performed a paired, lifestyle-balanced analysis of the effect of IgA on the gut microbiota composition and functionality based on fecal samples from individuals with IgAD and IgA-sufficient household members (n = 100), involving quantitative shotgun metagenomics, species-centric functional annotation of gut bacteria, and strain-level analyses. We supplemented the data set with 32 individuals with IgAD and examined the influence of IgA-autoantibody status on the composition and functionality of the gut microbiota. RESULTS: The gut microbiota of individuals with IgAD exhibited decreased richness and diversity and was enriched for bacterial species encoding pathogen-related functions including multidrug and antimicrobial peptide resistance, virulence factors, and type III and VI secretion systems. These functional changes were largely attributed to Escherichia coli but were independent of E coli strain variations and most prominent in individuals with IgAD with IgA-specific autoreactive antibodies. CONCLUSIONS: The microbiota of individuals with IgAD is enriched for species holding increased proinflammatory potential, thereby potentially decreasing the resistance to gut barrier-perturbing events. This phenotype is especially pronounced in individuals with IgAD with IgA-specific autoreactive antibodies, thus warranting a screening for IgA-specific autoreactive antibodies in IgAD to identify patients with IgAD with increased risk for gastrointestinal implications.

Selective Immunoglobulin A Deficiency and the Microbiome.

Selective immunoglobulin A (IgA) deficiency (SIgAD) is the most common primary immunodeficiency disease with a prevalence of about 1:500 individuals. SIgAD is heterogeneous, though thought to be due to a defect in the differentiation of IgA-bearing B lymphocytes into IgA-secreting plasma cells which provide a first line of defense against bacterial and viral pathogens. Although SIgAD was for a long time considered asymptomatic, longitudinal studies have revealed that about 80% of patients are symptomatic and can present with a range of phenotypes including allergic disease, recurrent bacterial respiratory tract infections, gastrointestinal disorders, and autoimmune diseases. Secretory IgA has been shown to play a critical role in maintaining immune homeostasis in the gut by determining the composition of and directing the function of gut microbiota. Patients with SIgAD demonstrate gut dysbiosis with enriched proinflammatory phyla that is only partially compensated for by IgM and IgG. In this review, we will discuss what is known about the microbiome of individuals with SIgAD and how this might provide insights into therapeutics and monitoring in these patients.

Preface Special Issue: Microbiome-Immune System Interactions.

Body homeostasis, immune response to microbial infections or vaccination, control of cancer onset or autoimmune or inflammatory diseases, as well as autism or other behavioral disorders, among other examples, are now recognized to be associated with the complex constitution of the body's microbiome. Recent findings demonstrate that the microbial composition, i.e., pathogenic, symbionts, and commensal viruses, bacteria, or yeast mainly in the gut, is strongly associated with susceptibility/resistance to several classes of diseases or its therapeutic response. This Special Issue focuses on the processes that link the human microbiome to three classes of diseases; immunodeficiency, autoimmunity, and cancer. Review articles cover aspects of the recent progress in selective immunoglobulin A (IgA) deficiency, Sjörgren's syndrome, breast cancer.

The Prevalence of Selective and Partial Immunoglobulin A Deficiency in Patients with Autoimmune Polyendocrinopathy.

BACKGROUND: Autoimmune disorders are reported as presenting signs in patients with immunoglobulin A (IgA) deficiency. Herein, we aim to evaluate serum IgA among patients with autoimmune polyendocrinopathy. METHODS: Patients with two or more autoimmune endocrinopathies were selected and the serum IgA levels were measured. Patients with an isolated low serum IgA (<7 mg/dL) after exclusion of other causes of hypogammaglobulinemia were considered as selective IgA deficiency (SIgAD), while partial IgA deficiency (PIgAD) was defined as IgA levels below lower limits of IgA normal range for age but higher than 7 mg/dL. RESULTS: Fifty-three patients (19 [35.8%] male and 34 [64.2%] female) with autoimmune polyendocrinopathy enrolled in the study. Parental consanguinity and positive family history of autoimmunity were reported in 38.0% and 52.9% of patients, respectively. Overall, IgA deficiency was observed in 5 (9.4%) patients including PIgAD in 3 (5.7%) and SIgAD in 2 (3.8%) patients. Among IgA deficient patients, the first autoimmune disorder was developed at earlier ages (p = .002), and the prevalence of infection (p = .002), lymphoproliferation (p = .021), and overlap between insulin-dependent diabetes mellitus and autoimmune thyroiditis (p = .032) were significantly higher than patients with normal IgA. Also, the number of autoimmune comorbidities was closely correlated with the occurrence of IgA deficiency (p = .008). CONCLUSION: The prevalence of IgA deficiency in patients with autoimmune polyendocrinopathy is higher than that in the general population. In these patients, immunologic workup may lead to early diagnosis of inborn error of immunity, which can positively impact the evolution of complications and even management of the autoimmune disorders.

IgA Deficiency Is Not Systematically Ruled Out in Patients Undergoing Celiac Disease Testing.

BACKGROUND: Guidelines for celiac disease (CD) testing recommend total serum IgA determination alongside anti-transglutaminase IgA antibodies. It is not well known if lack of serum IgA determination is a common finding in clinical practice. AIM: To determine the prevalence of lack of serum IgA determination among patients screened for celiac disease. MATERIALS AND METHODS: We identified all subjects who underwent serum anti-transglutaminase IgA and/or other CD-related antibodies determination at a single teaching hospital in Buenos Aires from October 2019 to February 2020. Medical records were reviewed to select adult patients who were tested for celiac disease. The primary outcome was the proportion of patients with inadequate testing for celiac disease due to lack of serum IgA determination. We retrieved the following variables from each patient's record: age, gender, body mass index, symptoms present at screening, first-grade family history of CD, history of type-1 diabetes mellitus, autoimmune hypothyroidism, Down's syndrome. RESULTS: Overall, 1122 patients were included for analysis. Lack of serum IgA determination prevalence was 20.49%. Among patients who did have serum IgA determination, the prevalence of IgA deficiency was 5.16%. The following variables were independently associated with a significantly increased odds of serum IgA determination: diarrhea [OR 1.55 (1.01-2.34)] and abdominal pain [OR 2.28 (1.44-3.63)]; higher body mass index [OR 0.91 (0.85-0.98)], osteoporosis [OR 0.49 (0.28-0.89)], hypothyroidism [OR 0.18 (0.07-0.45)], arthralgia/arthritis [OR 0.47 (0.27-0.85)], or testing by endocrinologist [OR 0.46 (0.23-0.91)] and gynecologist [OR 0.14 (0.06-0.31)] were inversely associated. CONCLUSION: IgA deficiency is not systematically ruled out in a relatively high proportion of patients undergoing serological screening of celiac disease.

Berardinelli Seip Syndrome: A rare case report.

Berardinelli Seip Congenital Lipodystrophy (BSCL) or Congenital Generalized Lipodystrophy (CGL) is one of the four subgroups of lipodystrophy syndrome which is characterized by varying degrees of loss of adipose mass in the body. It is an extremely rare autosomal recessive disorder and commonly reported clinical presentations include muscular hypertrophy, gigantism, hepatomegaly, impaired glucose tolerance, acanthosis nigricans, hypertriglyceridaemia, cardiomyopathy, intellectual impairment, bone cysts and phlebomegaly. We present a case of a 4.5 years old male child born to consanguineous parents, presented with pneumonia. There was history of recurrent diarrhea and chest infection in the past. He had acromegaly like features, hirsutism, firm hepatomegaly, a well defined bone cyst in proximal right femur, pancytopenias with normal bone marrow biopsy report, hypertriglyceridemia and selective IgA deficiency. This is the first case of BSCL, reported in Pakistan with a bone cyst and IgA deficiency. Such patients need to be identified and monitored for complications like diabetes mellitus and hypertrophic cardiomyopathy.

Selective IgA Deficiency and Allergy: A Fresh Look to an Old Story.

Selective IgA deficiency (SIgAD) is the most common human primary immune deficiency (PID). It is classified as a humoral PID characterized by isolated deficiency of IgA (less than 7 mg/dL but normal serum IgG and IgM) in subjects greater than 4 years of age. Intrinsic defects in the maturation of B cells and a perturbation of Th cells and/or cytokine signals have been hypothesized to contribute to SIgAD pathogenesis. The genetic basis of IgA deficiency remains to be clarified. Patients with SIgAD can be either asymptomatic or symptomatic with clinical manifestations including allergy, autoimmunity and recurrent infections mainly of the respiratory and gastrointestinal tract. Studies analyzing allergy on SIgAD patients showed prevalence up to 84%, supporting in most cases the relationship between sIgAD and allergic disease. However, the prevalence of allergic disorders may be influenced by various factors. Thus, the question of whether allergy is more common in SIgAD patients compared to healthy subjects remains to be defined. Different hypotheses support an increased susceptibility to allergy in subjects with SIgAD. Recurrent infections due to loss of secretory IgA might have a role in the pathogenesis of allergy, and vice versa. Perturbation of microbiota also plays a role. The aim of this review is to examine the association between SIgAD and atopic disease and to update readers on advances over time at this important interface between allergy and SIgAD.

Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia.

Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978).

Autoimmune Inner Ear Disease among Patients with Selective IgA Deficiency.

OBJECTIVES: Autoimmune inner ear disease (AIED) is a distinct clinical entity from sudden sensorineural hearing loss. The purpose of this study was to investigate the clinical characteristics of AIED in patients with selective IgA deficiency (sIgAD). MATERIALS AND METHODS: This retrospective observational study was based on data from the Leumit Healthcare Services database in Israel. We searched all subjects aged ≥12 years who had undergone serum total IgA measurements during 2004-2014 for any reason. The sIgAD patients included all subjects with serum IgA of ≤7 mg/dL (0.07 g/L). A control group was randomly sampled from the full study population (n ≈ 730,000) with a case-control ratio of 10 controls for each case (1:10). RESULTS: Among 347 subjects with sIgAD, we identified 9 patients with concomitant AIED (sIgAD + AIED group). This group was characterized by a higher prevalence of allergic diseases (8 patients; 88.9%) than sIgAD patients without AEID (sIgAD + AIED group; 153 patients; 45.2%; p = 0.014). Both systemic diseases (3 patients; 33.3%) and organ-specific autoimmune diseases (7 patients; 77.8%) were more prevalent in the sIgAD + AIED group (sIgAD + AIED group: 19 patients 5.5%, p = 0.015; sIgAD - AEID group: 76 patients, 21.9%, p < 0.001), with an OR of 8.39 (1.94-36.19; p = 0.004). sIgAD patients with and without AIED were characterized by a higher prevalence of documented episodes of acute otitis media, allergic diseases, and autoimmune diseases than the control group. CONCLUSION: The study exposes a significant association between AIED and sIgAD. We believe that sIgAD has to be excluded in AIED patients.

Diagnosing and Monitoring Celiac Patients with Selective IgA Deficiency: Still an Open Issue.

Although, the association between celiac disease (CD) and selective immunoglobulin A deficiency (SIgAD) has been known for more than fifty years, the procedures for diagnosing and monitoring patients with both conditions are still far from definitive. When serological markers were introduced as pre-bioptic investigations, it was immediately clear that searching for specific IgA antibodies without checking total serum IgA could lead to a failure in diagnosing IgA-deficient CD patients, while specific IgG antibodies could be useful as additional tests, because they are frequently found in the serum of affected patients. Nonetheless, until recently the diagnosis of CD in IgA-deficient patients was based on the few, fragmentary and often contradictory data available in literature. The introduction of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines in 2012 provided the current criteria for diagnosing CD in IgA-deficient patients, although some issues remained open, such as the selection of patients who should undergo specific IgG antibody testing and the choice of the most reliable IgG-based test for both diagnosis and follow-up. A real-life study recently assessed the impact of the 2012 ESPGHAN guidelines in diagnosing and monitoring CD in SIgAD patients, highlighting several pitfalls that can lead to operational uncertainties and difficulties in patient management. In the present report, the evolution of diagnostic tools and criteria for CD in SIgAD patients has been critically assessed, both strengths and open issues have been highlighted, and future perspectives for improving the current diagnostic protocols have been suggested.

Abnormal Peyer patch development and B-cell gut homing drive IgA deficiency in Kabuki syndrome.

BACKGROUND: Kabuki syndrome (KS) is commonly caused by mutations in the histone-modifying enzyme lysine methyltransferase 2D (KMT2D). Immune dysfunction is frequently observed in individuals with KS, but the role of KMT2D in immune system function has not been identified. OBJECTIVE: We sought to understand the mechanisms driving KS-associated immune deficiency (hypogammaglobulinemia [low IgA], splenomegaly, and diminished immunization responses). METHODS: We performed a comprehensive evaluation of humoral immunity and secondary lymphoid tissues in an established KS (Kmt2d+/ßGeo) mouse model and validated select findings in a patient with KS. RESULTS: Compared with wild-type littermates, Kmt2d+/ßGeo mice demonstrated deficiencies in multiple B-cell lineages and reduced serum IgA and elevated IgM levels across multiple ages. The bone marrow, spleen, and intestine of Kmt2d+/ßGeo mice contained diminished numbers of IgA-secreting cells, while elevated germinal center B cells were found in the mesenteric lymph node and Peyer patches. Kmt2d+/ßGeo mice have decreased size and numbers of Peyer patches, a finding confirmed in human samples. We identified deficiency of Itgb7 RNA and protein expression, a gene encoding an adhesion protein that mediates intestinal homing, and we demonstrated KMT2D-dependent control of ITGB7 expression in a human cell line. CONCLUSIONS: Kmt2d haploinsufficiency has broad deleterious effects on B-cell differentiation, specifically hampering gut lymphocyte homing and IgA+ plasma cell differentiation. Intestinal lymphoid defects caused by ITGB7 deficiency have not previously been recognized in KS, and these results provide new mechanistic insights into the pathogenesis of KS-associated immune deficiency.

[Prevalence and characteristics of selective IgA deficiency in celiac patients]. / Prevalencia y características de la deficiencia selectiva de IgA en pacientes celíacos.

INTRODUCTION: Celiac disease is a multisystemic autoimmune disease that mainly affects the small intestine. Selective Immunoglobulin A deficiency is the most common primary immunodeficiency in the general population, with an incidence of 1%. It is estimated that it affects 2%-3% of celiac disease and 6.5% of patients with this deficit have celiac disease, observing the important association between both. OBJECTIVES: To determine the prevalence of selective Immunoglobulin A deficiency in celiac patients. Describe the clinical, serological, and histological presentation and its association with autoimmune diseases. MATERIALS AND METHODS: Cross-sectional, descriptive, and retrospective study in celiac patients with Immunoglobulin A dosing in the period from March 2005 to March 2020, at the Gastroenterology Clinic, Hospital de Clínicas, Montevideo-Uruguay. RESULTS: 343 patients were included. Seven patients presented selective Immunoglobulin A deficiency (2%). All were female with a mean age of 20 years (4-36). Selective total immunoglobulin A deficiency was observed in 6 patients (85%) and only 1 (15%) had partial deficiency. Tissue transglutaminase antibody immunoglobulin A and antiendomysium antibody were negative in patients with selective total immunoglobulin A deficiency and positive in those with partial deficiency. All presented villous atrophy, gastrointestinal symptoms, and a lower incidence of autoimmune diseases compared to the reference literature. CONCLUSIONS: The prevalence of selective immunoglobulin A deficiency in this celiac population (2%) is similar to that reported in other populations, reaffirming the importance of including immunoglobulin A dosing for the diagnosis of CD.

FEATURES OF DEVELOPMENT OF GENERALIZED PERIODONTITIS IN PERSONS WITH SECRETORY IMMUNOGLOBULIN A DEFICIENCY AND ITS TREATMENT (LITERATURE REVIEW).

OBJECTIVE: The aim: To present data on the possibility of occurrence and active progression of generalized periodontitis in persons with secretory immunoglobulin A deficiency and possible methods of its correction. PATIENTS AND METHODS: Мaterials and methods: Analytical elaboration of scientific and medical literature based on the immunological aspect of generalized periodontitis. CONCLUSION: Conclusions: The deficiency of secretory immunoglobulin A may occur in cases of primary or secondary insufficiency of the immune system. Selective IgA deficiency is an example of primary insufficiency of the immune system. Secondary immunodeficiency disorders is a clinical and immunological syndrome that develops against the background of a previously normally functioning immune system, characterized by a steady decrease in quantitative or functional indicators of specific or(and) nonspecific factors of immunoresistance. Insufficient awareness of dentists about certain aspects of the etiology and pathogenesis of generalized periodontitis leads to deterioration of treatment results.

Unusual phenotype in patients with a hypomorphic mutation in the DCLRE1C gene: IgG hypergammaglobulinemia with IgA and IgE deficiency.

The nuclease Artemis is a enzyme for V(D)J recombination allowing for the creation of T and B lymphocytes as well as for the repair of radiation-induced DNA double strand breaks encoded by the DCLRE1C gene. Artemis-null mutations are a known cause of severe combined immunodeficiencies (SCIDs) with radiosensitivity. Hypomorphic mutations in Artemis have been reported to cause a "leaky SCID"" phenotype, typically with hypogammaglobulinemia. We present four patients, all harboring the same unique hypomorphic mutation in the DCLRE1C gene, an 8-base pair insertion (c.1299_1306dup, p.Cys436*) presenting with a relatively mild phenotype including pulmonary infectious EBV-related lymphoproliferative diseases, an autoimmune phenomenon. Non-typical findings of IgG hypergammaglobulinemia accompanied by IgA and IgE deficiency were recorded in all patients. The typical viral, fungal, and opportunistic infections were absent, and patients reached a relatively old age.

The Utility of IgA-Based Serologic Markers in Diagnosing Celiac Disease in Children 24 Months of Age or Younger.

Current screening guidelines in North America for celiac disease recommend additional IgG based testing for younger children. Our multicenter retrospective study showed that the anti-tissue transglutaminase IgA antibody test should be the recommended initial test in all children, including those ≤24 months of age.