Dental Treatment Under General Anesthesia With Nasal Intubation in a Patient With Selective Immunoglobulin A Deficiency.

Immunoglobulin A (IgA) deficiency is one of the most common immune disorders characterized by increased susceptibility to infections, especially involving the respiratory tract and mucosal surfaces of the mouth, gingiva, and nasal sinus. Because dental surgery and general anesthesia may pose an increased risk for systemic infections, management of IgA-deficient patients requires caution during dental procedures and intubated general anesthesia. We report a 5-year-old female patient with IgA deficiency who underwent extraction of 18 deciduous teeth under general anesthesia. Antibiotic prophylaxis and antiseptic mouthwash were used perioperatively to reduce bacteremia risks. Nasotracheal intubation was carefully performed after applying topical disinfectants and epinephrine-containing gauze packing into the nasal cavity to minimize trauma. The patient was carefully monitored overnight in the hospital and discharged without any signs or symptoms of infection the next day. Dental anesthesia providers must be aware of the potential implications for safe practice when managing patients with IgA deficiency.

The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency.

Selective immunoglobulin A deficiency (SIgAD) is the most common primary immunodeficiency, defined as an isolated deficiency of IgA (less than 0.07 g/L). Although the majority of people born with IgA deficiency lead normal lives without significant pathology, there is nonetheless a significant association of IgA deficiency with mucosal infection, increased risks of atopic disease, and a higher prevalence of autoimmune disease. To explain these phenomena, we have performed an extensive literature review to define the geoepidemiology of IgA deficiency and particularly the relative risks for developing systemic lupus erythematosus, hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, and vitiligo; these diseases have strong data to support an association. We also note weaker associations with scleroderma, celiac disease, autoimmune hepatitis, immune thrombocytopenic purpura, and autoimmune hemolytic anemia. Minimal if any associations are noted with myasthenia gravis, lichen planus, and multiple sclerosis. Finally, more recent data provide clues on the possible immunologic mechanisms that lead to the association of IgA deficiency and autoimmunity; these lessons are important for understanding the etiology of autoimmune disease.

Hematologic Manifestations in Celiac Disease-A Practical Review.

Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency.

Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients.

Fifteen-minute consultation: The child with an incidental finding of low IgA.

Low or absent immunoglobulin A (IgA) levels are frequently found in children in whom immunodeficiency is not suspected. IgA deficiency is the most common primary immunodeficiency disorder in the UK affecting approximately 1 in 600 people. Isolated IgA deficiency is often identified coincidentally when investigating a child for conditions such as coeliac disease. The aim of this article is to provide a structured approach to the history, investigation and management of an isolated IgA deficiency.

The long and winding road to IgA deficiency: causes and consequences.

INTRODUCTION: The most common humoral immunodeficiency is IgA deficiency. One of the first papers addressing the cellular and molecular mechanisms underlying IgA deficiency indicated that immature IgA-positive B-lymphocytes are present in these patients. This suggests that the genetic background for IgA is still intact and that class switching can take place. At this moment, it cannot be ruled out that genetic as well as environmental factors are involved. Areas covered: A clinical presentation, the biological functions of IgA, and the management of IgA deficiency are reviewed. In some IgA deficient patients, a relationship with a loss-of-function mutation in the TACI (transmembrane activator and calcium-modulating cyclophilin ligand interaction) gene has been found. Many other genes also have been associated. Gut microbiota are an important environmental trigger for IgA synthesis. Expert commentary: Expression of IgA deficiency is due to both genetic and environmental factors and a role for gut microbiota cannot be excluded.

A comparison of B cell subsets in primary immune deficiencies that progress with antibody deficiency and age-matched healthy children

BACKGROUND: The objective of this study was to examine the B lymphocyte subsets in primary immunodeficiency that progress with antibody deficiency. METHODS: The patients' naive, memory, class-switched memory and non-switched memory B cells were compared with those of healthy individuals of matching ages using flow cytometry. RESULTS: A total of 67 patients with antibody deficiency and 28 healthy children of matching ages were included in the study. The median age of the patients was six years (min-max: 1-24) and 40 (59.7%) were male. The median age of the healthy controls was again six years (min-max: 1-17) and 12 (42.8%) were male. Patients with common variable immunodeficiency had higher relative counts of naive cells when compared with the control group; however, they were found to have lower relative counts of memory, relative and absolute counts of non-switched and relative counts of switched B lymphocytes (p = 0.001, 0.023, 0.003-0.003, 0.001, respectively). In patients with selective IgA deficiency, similar to patients with common variable immunodeficiency, the relative counts of naive cells were found to be higher, while the relative counts of memory and relative and absolute counts of non-switched B lymphocytes were found to be lower when compared with the control group (p = 0.011, 0.032, 0.006-0.009, respectively). Although patients with selective IgM deficiency had higher relative counts of naive B cells when compared with the control group, they had lower relative and absolute counts of non-switched B lymphocytes (p = 0.008-0.016). CONCLUSIONS: The B lymphocyte subsets of patients with selective IgA deficiency are largely similar to those of patients with common variable immunodeficiency. Both illness groups exhibit low levels of memory B cells

No disponible

[VACCINE-ASSOCIATED PARALYTIC POLIOMYELITIS IN RUSSIAN FEDERATION DURING THE PERIOD OF CHANGES IN VACCINATION SCHEDULE (2006-2013 yy.)].

The results of virologic testing of clinical materials and epidemiological analysis of vaccine-associated paralytic poliomyelitis (VAPP) cases obtained in 2006-2013 during AFP surveillance are presented. Among the 2976 cases of AFP 30 cases were VAPP. 15 cases were observed in OPV recipients, whereas 15 cases were observed in non-vaccinated contacts. The age of the patients varied from 4 months to 5.5 years (13.6 ± 12.4 months old). Children younger than 1 year constituted 63.3% of the group; boys were dominant (73.3%); 53.3% of children were vaccinated with OPV; the time period between receipt of OPV and onset of palsy was from 2 to 32 days (18.7 ± 8.2). Lower paraparesis was documented in 48.3% of patients; lower monoparesis in 37.9%; upper monoparesis, in 6.9%; tetraparesis with bulbar syndrome, in 6%. The majority of the patients (85.7%) had an unfavorable premorbid status. The violations of the humoral immunity were found in 73.9% cases: CVID (52.9%), hypogammaglobulinemia (41.2%); selective lgA deflciency (5.9%). In 70.6% cases damage to humoral immunity was combined with poor premorbid status. The most frequently observed (76%, p < 0.05) represented the single type of poliovirus--type 2 (44%) and type 3 (32%). All strains were of the vaccine origin, the divergence from the homotypic Sabin strains fell within the region of the gene encoding VPI protein, which did not exceed 0.5% of nucleotide substitutions except vaccine derived poliovirus type 2--multiple recombinant (type 2/type 3/ type 2/type 1) with the degree of the divergence of 1.44% isolated from 6-month old unvaccinated child (RUS08063034001). The frequency of the VAPP cases was a total of 1 case per 3.4 million doses of distributed OPV in 2006-2013; 2.2 cases per 1 million of newborns were observed. This frequency decreased after the introduction of the sequential scheme of vaccination (IPV, OPV) in 2008-2013 as compared with the period of exclusive use of OPV in 2006-2007: 1 case per 4.9 million doses, 1.4 cases per million newborns and 1 case per 1.9 million doses, 4.9 cases per 1 million newborns, respectively. The study has been financed from Russian Federation budget within the framework of the Program for eradication of poliomyelitis in the Russian Federation, WHO Polio eradication initiative, WHO's European Regional Bureau, Russian Foundation for Basic Research (project No. 15-15-00147).

Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency - a case report.

We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes.

[Importance of selective immunoglobulin A deficiency]. / Importancia del déficit selectivo de inmunoglobulina A.

Selective IgA deficiency is the most common primary immunodeficiency. Little is known about the pathogenetic mechanisms leading to this disease. It is estimated that the incidence of this disease in Spain is 1:163. We report 3 cases diagnosed in Primary Care. Most people with selective IgA deficiency are usually asymptomatic and are diagnosed by chance, but patients with recurrent respiratory infections; gastrointestinal, allergic and autoimmune diseases can be associated with this disease. Although there is no treatment at present, its importance lies in the association with different diseases, such as coeliac disease or idiopathic thrombocytopenic purpura. Another important feature is the risk of anaphylaxis after transfusion, and the possible progression to Common Variable Immunodeficiency. It is important to know the vaccines that we can use due to the risk of disease.

Asthma and risk of selective IgA deficiency or common variable immunodeficiency: a population-based case-control study.

OBJECTIVE: To determine the association between a history of asthma and a diagnosis of selective IgA deficiency (sIgAD)/common variable immunodeficiency (CVID). PATIENTS AND METHODS: This population-based case-control study included residents of Olmsted County, Minnesota, who met the Pan-American Group for Immunodeficiency/European Society for Immunodeficiencies diagnostic criteria for sIgAD/CVID between January 1, 1964, through December 31, 2008. Each case had 4 age- and sex-matched controls (2 from the community and 2 from a list of individuals who had undergone an immune work-up). We ascertained asthma status by applying predetermined criteria for asthma. RESULTS: We identified 39 cases: 26 (66.7%) had sIgAD and 13 (33.3%) had CVID. Of the 39 cases, 51.3% were men (n=20) and 97.1% were white (33 of 34 patients). The mean age at the index date (the time when criteria were met) of sIgAD/CVID was 34.2 years. Of the 39 cases, 9 (23.1%) had a history of asthma before the index date of sIgAD/CVID; of the 156 controls, 16 (10.3%) had a history of asthma before the index date (odds ratio, 2.77; 95% CI, 1.09-7.06; P=.03). A history of asthma (before or after the index date of sIgAD/CVID) was more prevalent in sIgAD/CVID cases (30.8%; n=12) than in matched controls (11.5%; n=18) (odds ratio, 3.57; 95% CI, 1.50-8.51; P=.01). CONCLUSION: Asthmatic patients are more likely to have a diagnosis of sIgAD/CVID than nonasthmatic individuals. This association may potentially account for the increased risks of bacterial infections in some individuals with asthma.

Niki de Saint Phalle's lifelong dialogue between art and diseases: psychological trauma of sexual abuse, transient selective IgA deficiency, occupational exposure to toxic plastic material, chronic lung disease, rheumatoid arthritis.

The French artist Niki de Saint Phalle (1930-2002) is one of the most famous female painter and sculptor of the 20th century. Her eventful live was full of emotional and physical burdens such as abuse by the father as a adolescent, early separation from family, nervous collapse, turbulent relationship with the artist Jean Tinguely, and last not least serious diseases. The psychological trauma of sexual abuse together with a "nervous breakdown" years later was the start of a life as an artist and is also a key to her art of the early years. She was affected from rheumatoid arthritis (RA) and was treated over 20 years with prednisolone and antimalarials leading to a good functional outcome and limited erosions of the wrist joint. Additionally, she had lifelong pulmonary disorders finally leading to death, which she attributed to polyester, the material used for her sculptures. An analysis of medical documents collected by her and provided by treating physicians gives another surprising explanation: selective IgA deficiency with multiple recurrent respiratory infections, asthma, milk intolerance, autoimmune thyroiditis, and RA compatible with hypogammaglobulinemia. Very unique in case of Niki de Saint Phalle is that IgA deficiency was transient. Nevertheless, it may be possible that the occupational exposure with art materials (polystyrene, polyester) has contributed in part or temporarily to her health problems. Altogether, her enormous artistic productivity represents an outstanding example of creative coping with RA and other lifelong health problems.

Hypothyroidism and levothyroxine-responsive liver dysfunction in a patient with ring chromosome 18 syndrome.

BACKGROUND: Ring chromosome 18 [r18] is a rare constitutional chromosomal aberration syndrome, characterized by dysmorphic face, hypoactivity, short stature, and delayed development. Autoimmune thyroiditis and immunoglobulin (Ig) A deficiency are occasionally associated with chromosome-18 deletion syndromes. SUMMARY: Here, we report a 2-year-old male child with r(18) syndrome and a selective IgA deficiency (<1.6 mg/dL, reference range [rr]: 20-149), who developed hypothyroidism and liver dysfunction. Thyroid function tests (thyroid-stimulating hormone [TSH]: 1031 µIU/mL, rr 0.43-4.0; free triiodothyronine: 0.52 pg/mL, rr 2.37-4.65; free thyroxine: 0.11 ng/dL, rr 1.03-2.00) and positive thyroid antibodies (anti-TSH receptor 1.7 IU/L, cut-off index [coi]: <1.0, antithyroid peroxidase 171 IU/mL, coi <0.3, and antithyroglobulin 2.8 IU/mL, coi <0.3) indicated autoimmune hypothyroidism. Elevated levels of aspartate aminotransferase (AST, 240 IU/L, rr 17-39) and alanine aminotransferase (ALT, 315 IU/L, rr 4-23), but negative antibodies against LKM and mitochondrial M2, suggested no autoimmune hepatitis. Transaminase levels became normalized after he was given levothyroxine therapy to achieve the euthyroid state, but they repeatedly became elevated when levothyroxine was inadvertently discontinued (peak AST=409 IU/L; peak ALT=390 IU/L). A maintenance dose of levothyroxine has effectively maintained the euthyroid state and normalized liver function tests despite no immunosuppressive therapy. CONCLUSIONS: The r18 patient with autoimmune hypothyroidism and IgA deficiency suffered from idiopathic hepatitis. The liver dysfunction was associated with hypothyroidism that resolved with thyroid hormone treatment. While the former combination has been described, the latter has not. The reason for the development of hepatitis in association with hypothyroidism is unexplained. However, we postulate that it might be related, in ways that are not clear, to the deleted genes of r18.

Immune status is more affected by age than by carotenoid depletion-repletion in healthy human subjects.

Prospective studies have indicated an age-related impairment of the immune response. Carotenoids have been hypothesised to enhance immune cell function. The aim of the present study was to describe the age-related effects and the impact of in vivo dietary carotenoid depletion and repletion on specific and non-specific immunity. A total of ninety-eight healthy male subjects (aged 20-75 years) received a carotenoid-depleted diet for 3 weeks and were then supplemented daily for 5 weeks with 30 mg ß-carotene, 15 mg lycopene and 9 mg lutein. Blood samples were collected at study entry, after depletion and supplementation, and biomarkers of immune status were determined. We found that serum IgA levels were positively correlated with ageing. Lymphocyte phenotyping indicated an increase with age in the memory T-helper cell subpopulation (CD4⁺CD45RO⁺) concomitantly with a decrease in naive T-helper cells (CD4⁺CD45RA⁺). A significant increase in the natural killer cells subpopulation and a small decrease in B lymphocytes were also observed, especially for the oldest volunteers. From ex vivo cell function exploration, a positive correlation was observed between age and IL-2 production of phytohaemagglutinin-stimulated lymphocytes. Neutrophils' bactericidal activity was significantly impaired with age (from 50 years) and was modulated by carotenoid status. An age effect was found on neutrophils' spontaneous migration but not on directed migration. Immune response in healthy human subjects is mostly affected by age rather than by dietary carotenoid depletion and repletion. Even in carefully selected healthy volunteers, some age-related immune changes occur predominantly from 50 years onwards. This immunosenescence could generate a loss in the immune system adjustment capacity.