Immunoglobulin A Deficiency Publications (4110)


Immunoglobulin A Deficiency Publications

Eur J Gastroenterol Hepatol
Eur J Gastroenterol Hepatol 2017 Jan 11. Epub 2017 Jan 11.
aFirst Department of Internal Medicine, Coeliac CentreDepartments of bClinical BiochemistrycBiometry and Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. Read More

Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed.
Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients.
Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

Clin. Exp. Immunol.
Clin Exp Immunol 2017 Jan 11. Epub 2017 Jan 11.
Immunodeficiency Clinic, Medical Outpatient Unit and Immunodeficiency Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.

There are no published large-scale epidemiologic studies regarding the prevalence of skin diseases in patients with selective immunoglobulin A (IgA) deficiency (sIgAD). The purpose of this study was to investigate the prevalence of dermatological diseases in patients with sIgAD.
This retrospective matched case-control study was based on data from the Leumit Healthcare Services data base (approximately 725,000 residents of Israel), which was searched for all subjects aged ≥12 years who had undergone serum total IgA measurements during 2004-14 for any reason. Read More

The case group included subjects with sIgAD. The control A group was randomly sampled from those subjects in whom an IgA was drawn (n ≈ 725,000), with a ratio of 10 controls for every case (1:10). The control A group was randomly sampled from those subjects in whom an IgA was drawn (n = 104,729) and the control B group was randomly sampled from the full study population (n ≈ 725,000), with a ratio of 10 controls for every case (1:10). Comorbidity was compared between the study groups.
The sIgAD group was characterized: 1) By a higher prevalence of atopic dermatitis (AD) (16 [4.6 %]) than the control A group (76 [2.1 %]; p = 0.004 and the control B group (64 [1.9 %]; p = 0.002). 2) By higher prevalence of acne (69 [19.9 %]) than the control A group (516 [13.8 %]; p = 0.013) and control B group (494 [14.2 %]; p < 0.001). 3) By higher rate of chronic spontaneous urticaria (CSU) (17 [4.9 %)] than in the control A group (31 [0.9 %], with odds ratio 5.54 [3.04-10.13]; p < 0.001) and the control B group (28 [0.8 %]; p < 0.001).
sIgAD is characterized by a higher prevalence of AD, CSU and acne.

Int J Surg Case Rep
Int J Surg Case Rep 2016 Nov 22;30:69-72. Epub 2016 Nov 22.
University, Josip Juraj Strossmayer, Osijek University Hospital Centre, Clinic for Internal Medicine, Josip Huttler 4, Osijek, 31 000, Croatia.
J. Allergy Clin. Immunol.
J Allergy Clin Immunol 2016 Dec 1. Epub 2016 Dec 1.
Department of Pediatrics and Developmental Biology, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. Electronic address:

Ikaros, which is encoded by IKZF1, is a transcriptional factor that play a critical role in hematopoiesis. Somatic IKZF1 alterations are known to be involved in the pathogenesis of leukemia in human subjects. Recently, immunodeficiency caused by germline IKZF1 mutation has been described. Read More

We sought to describe the clinical and immunologic phenotypes of Japanese patients with heterozygous IKZF1 mutations.
We performed whole-exome sequencing in patients from a dysgammaglobulinemia or autoimmune disease cohort and used a candidate gene approach in 4 patients. Functional and laboratory studies, including detailed lymphopoiesis/hematopoiesis analysis in the bone marrow, were performed.
Nine patients from 6 unrelated families were identified to have heterozygous germline mutations in IKZF1. Age of onset was 0 to 20 years (mean, 7.4 years). Eight of 9 patients presented with dysgammaglobulinemia accompanied by B-cell deficiency. Four of 9 patients had autoimmune disease, including immune thrombocytopenic purpura, IgA vasculitis, and systemic lupus erythematosus. Nonautoimmune pancytopenia was observed in 1 patient. All of the mutant Ikaros protein demonstrated impaired DNA binding to the target sequence and abnormal diffuse nuclear localization. Flow cytometric analysis of bone marrow revealed reduced levels of common lymphoid progenitors and normal development of pro-B to pre-B cells.
Germline heterozygous IKZF1 mutations cause dysgammaglobulinemia; hematologic abnormalities, including B-cell defect; and autoimmune diseases.

Med. Sci. Monit.
Med Sci Monit 2016 Dec 6;22:4773-4778. Epub 2016 Dec 6.
Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.

Maintenance of a surface immune barrier is important for homeostasis in organs with mucosal surfaces that interface with the external environment; however, the role of the mucosal immune system in chronic lung diseases is incompletely understood.
We examined the relationship between secretory immunoglobulin A (SIgA) on the mucosal surface of small airways and parameters of inflammation and airway wall remodeling in chronic obstructive pulmonary disease (COPD).
We studied 1,104 small airways (<2 mm in diameter) from 50 former smokers with COPD and 39 control subjects. Read More

Small airways were identified on serial tissue sections and examined for epithelial morphology, SIgA, bacterial DNA, NF-κB activation, neutrophil and macrophage infiltration, and airway wall thickness.
Morphometric evaluation of small airways revealed increased mean airway wall thickness and inflammatory cell counts in lungs from COPD patients compared to control subjects, while SIgA level on the mucosal surface was decreased. However, when small airways were classified as SIgA-intact or SIgA-deficient, we found that pathological changes were localized almost exclusively to SIgA-deficient airways, regardless of study group. SIgA-deficient airways were characterized by: 1) abnormal epithelial morphology, 2) invasion of bacteria across the apical epithelial barrier, 3) NF κB activation, 4) accumulation of macrophages and neutrophils, and 5) fibrotic remodeling of the airway wall.
Our findings support the concept that localized, acquired SIgA deficiency in individual small airways of COPD patients allows colonizing bacteria to cross the epithelial barrier and drive persistent inflammation and airway wall remodeling, even after smoking cessation.

PLoS One 2016 29;11(11):e0167250. Epub 2016 Nov 29.
Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.

Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. Read More

The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD. Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls. BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls. NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation. When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM. We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway. Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients. This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.

The importance of iron deficiency as a public health problem is based ultimately on the seriousness of its consequences on health. The most extensively investigated consequences of iron deficiency involve work performance and immune function. The significance of the effects on work performance is generally accepted. Read More

In contrast, data on the influence of iron deficiency on immune function are often perceived as being confusing and contradictory.We aimed to evaluate the effect of iron deficiency anemia on humoral, cellular, nonspecific immunity, and also the effect on the cytokines that are the key factors of many immunologic steps.Forty children with iron deficiency anemia and 20 age and sex-matched healthy children were included. All children were subjected to full medical history, thorough clinical examination, complete blood count, iron indices (serum iron, serum total iron-binding capacity, serum ferritin, and transferrin saturation), immunoglobulin assay (IgA, IgG, and IgM), interleukin (IL)-6 serum level, study of T-lymphocyte subsets, and evaluation of phagocytic function of macrophages and oxidative burst activity of neutrophils.Patients had significantly lower IgG levels, IL-6, phagocytic activity, and oxidative burst of neutrophils than controls, although there was no significant difference between patients and controls with regard to other immunoglobulins and CD4/CD8 ratio. There was significantly positive correlation between serum iron and IL-6 serum level.We concluded that humoral, nonspecific immunity (phagocytic activity and oxidative burst), and the IL-6 are influenced in patients with iron deficiency anemia. Study of these abnormalities after correction of iron deficiency is strongly needed.

Orphanet J Rare Dis
Orphanet J Rare Dis 2016 Nov 25;11(1):159. Epub 2016 Nov 25.
The Ataxia Telangiectasia Clinical Center, Departments of Pediatrics, Medicine and Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Ataxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome.
The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births. Read More

A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations.
A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress.
The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene.
There are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing.
Antenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis.
Genetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted.
Treatment of the neurologic problems associated with A-T is symptomatic and supportive, as there are no treatments known to slow or stop the neurodegeneration. However, other manifestations of A-T, e.g. immunodeficiency, pulmonary disease, failure to thrive and diabetes can be treated effectively.