Search

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. [ABSTRACT FROM AUTHOR]

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) [ABSTRACT FROM AUTHOR]

Objective: Secreted IgA (SIgA) plays a central role in preventing bacterial and viral infections on mucosal surfaces by neutralizing toxins and viruses and inhibiting bacterial attachment to epithelial cells. However, the role of salivary SIgA antibodies (Abs) in regulating oral flora is still unknown. This study aimed to evaluate the association among oral bacteria, their metabolites and periodontitis in IgA-deficient (IgA KO) and wild-type (WT) control mice. Methods: Microcomputed tomography (micro-CT) analysis was used to assess alveolar bone resorption as a development of periodontitis. The bacterial profiles of saliva were determined using the next-generation sequencing assays. Furthermore, the metabolites in saliva were measured and compared using CE-TOFMS. Results: Salivary microbiota of IgA KO mice revealed a remarkably decreased frequency of Streptococcus, and increased percentages of Aggregatibacer, Actinobacillus, and Prevotella at the genus level when compared with those of WT. Compared to WT control mice of the same age, the level of alveolar bone loss was significantly increased in IgA KO mice, and infiltration of osteoclasts was found on the surface of the alveolar bone. The metabolome profile indicated that the metabolites of IgA KO mice had greater variability in carbon metabolic, urea cycle, and lipid pathways than WT mice. Conclusion: These results suggest that salivary SIgA plays an important role in regulating and maintaining normal oral microflora to prevent the development of periodontal disease. [ABSTRACT FROM AUTHOR]

Purpose: To explore the risk of infections in individuals with IgA deficiency compared to general population controls. Methods: In this nationwide prospective population-based cohort study, we used data on IgA levels (<0.07 g/L) from six university hospitals in Sweden to identify 2100 individuals with IgA deficiency. Individuals were diagnosed between 1980 and 2010. For each patient with IgA deficiency we identified 10 controls from the general population, matched on age, sex, and place of residence ( n = 18,653). Data on infections were obtained from the Swedish National Patient Register (including inpatient and hospital-based outpatient care) between 2001 and 2010. We defined infections as having a record of a relevant international classification of disease (ICD) code. Prevalences and prevalence ratios (PRs) were calculated. Results: Individuals with IgA deficiency were more likely to have a record of any infection (36.1 vs. 18.8 % in controls) corresponding to a PR of 2.4 (95%CI 2.2-2.6). We also noted statistically significant associations with IgA deficiency (all P-values <0.05) and respiratory tract infections (17.8 vs. 6.3 % in controls; PR = 3.2), gastrointestinal infections (6.0 vs. 1.8 % in controls; PR = 3.5), skin infections (4.1 vs. 2.2 % in controls; PR = 1.9), joint infections (0.48 vs. 0.24 % in controls; PR = 2.0; P = 0.052), sepsis (1.5 vs. 0.45 % in controls; PR = 3.4), meningitis (0.38 vs. 0.12 %, PR = 3.2), mastoiditis/otitis (2.1 vs. 1.1 % in controls; PR = 2.0), and urinary tract infections (6.1 vs. 3.4 % in controls; PR = 1.8). Conclusions: Individuals with IgA deficiency are at an increased risk of infections requiring hospital care. [ABSTRACT FROM AUTHOR]

Background: Recombination-activating gene (RAG) 1 and 2 deficiency is seen in patients with severe combined immunodeficiency (SCID) and Omenn syndrome. However, the spectrum of the disease has recently expanded to include a milder phenotype. Objective: We analyzed a 4-year-old boy who was initially given the diagnosis of selective immunoglobulin A deficiency (SIgAD) based on immunoglobulin serum levels without any opportunistic infections, rashes, hepatosplenomegaly, autoimmunity or granulomas. The patient was found to be infected with varicella zoster; however, the clinical course was not serious. He produced antiviral antibodies. Methods: We performed lymphocyte phenotyping, quantification of T cell receptor excision circles (TRECs) and kappa deleting recombination excision circles (KRECs), an analysis of target sequences of RAG1 and 2, a whole-genome SNP array, an in vitro V(D)J recombination assay, a spectratype analysis of the CDR3 region and a flow cytometric analysis of the bone marrow. Results: Lymphocyte phenotyping demonstrated that the ratio of CD4+ to CD8+ T cells was inverted and the majority of CD4+T cells expressed CD45RO antigens in addition to the almost complete lack of B cells. Furthermore, both TRECs and KRECs were absent. Targeted DNA sequencing and SNP array revealed that the patient carried a deletion of RAG1 and RAG2 genes on the paternally-derived chromosome 11, and two maternally-derived novel RAG1 missense mutations (E455K, R764H). In vitro analysis of recombination activity showed that both RAG1 mutant proteins had low, but residual function. Conclusions: The current case further expands the phenotypic spectrum of mild presentations of RAG deficiency, and suggests that TRECs and KRECs are useful markers for detecting hidden severe, as well as mild, cases. [ABSTRACT FROM AUTHOR]

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in Bruton's tyrosine kinase (BTK), and is characterized by markedly decreased numbers of blood B cells and an absence of all immunoglobulin isotypes. We performed whole exome sequencing in a male pediatric patient with dysgammaglobulinemia with IgA deficiency. Genetic analysis revealed a BTK missense mutation (Thr316Ala). To investigate whether a BTK mutation underlay this antibody deficiency with marked decrease of IgA in this patient, we performed functional analyses of B cells and phagocytes, and molecular analyses of somatic hypermutation and class switch recombination. The BTK missense mutation resulted in B cells with reduced BTK and high IgM expression. Equal proportions of CD19 and CD19 fractions were observed, and both included naïve and memory B cells. Calcium influx and phospholipase Cγ2 phosphorylation upon IgM stimulation were marginally impaired in CD19, but not in CD19 B cells. Similar to XLA patients, IgA transcripts showed low SHM levels, whereas IgG transcripts were hardly affected. Our analyses suggest that the BTK mutation likely underlies the disease in this case, and that hypomorphic BTK mutations can result in normal circulating B cell numbers, but specifically impair IgA responses. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of cancer in individuals with IgA deficiency compared with the general population. Methods: Prospective nationwide population-based cohort study. We identified 2320 individuals with IgA deficiency (IgA levels < 0.07 g/L) diagnosed between 1980 and 2010 in six Swedish university hospitals. Individuals with IgA deficiency were then matched on age, sex, place of residence, and year of diagnosis with up to 10 general population controls ( n = 23,130). Through linkage with the Swedish Cancer Register we calculated conditional hazard ratios (HRs) for cancer diagnosed after IgA deficiency diagnosis in patients without a previous cancer diagnosis. Results: During follow-up, 125 individuals with IgA deficiency (61/10,000 person-years) and 984 controls (47/10,000 person-years) developed cancer (HR 1.31; 95%CI = 1.09-1.58). In cause-specific analyses, we found an increased risk of any gastrointestinal cancer (HR = 1.64; 95%CI = 1.07-2.50), but not for lymphoproliferative malignancy (HR 1.68; 95%CI = 0.89-3.19). Relative risk estimates for overall cancer were very high in the first year of follow-up (overall: HR = 2.80; 95%CI = 1.74-4.49), but failed to reach statistical significance thereafter. IgA deficiency diagnosed in childhood ( n = 487) was not associated with overall cancer (HR = 3.26; 0.88-12.03). Conclusions: Individuals with IgA deficiency are at a moderately increased risk of cancer, with excess risks of gastrointestinal cancer. This excess risk is highest just after diagnosis suggesting a degree of surveillance bias. Children with IgA deficiency were at no increased risk of cancer but the statistical power was limited in subanalyses. [ABSTRACT FROM AUTHOR]

Purpose: Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD. Methods: Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE). Results: Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 ± 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate. Conclusions: Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off. [ABSTRACT FROM AUTHOR]

Purpose: Common variable immunodeficiency (CVID) is the most frequent form of primary symptomatic hypogammaglobulinemia. CVID patients display a number of abnormalities in lymphocyte subpopulations including chronic T-cell activation and decreased numbers of circulating CD4 T cells and NK cells. We and others have recently shown that CVID is associated with increased concentration of soluble CD14 (sCD14) and other factors indicating limited microbial translocation. Methods: To address the mechanisms of chronic immune activation in CVID, we performed a detailed analysis of cytokine serum levels in 36 patients with CVID, 52 patients with selective IgA deficiency (IgAD), and 56 healthy volunteers. Results: We show that CVID is associated with elevated serum levels of CXCL-10/IP-10, IL-1R antagonist, TNF-α, IL-10, IL-12 (p40), CCL-2/MCP-1, G-CSF, and CCL-11/eotaxin. The detected cytokine signature is consistent with an ongoing activation of cells of myeloid lineage. In contrast, the levels of cytokines typically produced by CD4 T helper cells of Th1 (IFN-γ, IL-2), Th2 (IL-9, IL-13), and Th17 (IL-17) subtypes were suppressed in CVID patients compared to healthy donors. Conclusions: Presented data suggest that the altered cytokine profile observed in patients with CVID may be attributed to the activation of monocyte-macrophage and granulocyte lineages, possibly driven by the translocation of bacterial components across the gastrointestinal or respiratory tracts mucosal barrier. [ABSTRACT FROM AUTHOR]

Background: Several autoimmune disorders have been linked to adverse pregnancy outcome. IgA deficiency shares many autoimmune traits, but its association with pregnancy outcome is unknown. Methods: Prospective population-based cohort study in Sweden of 613 mothers with IgA deficiency (IgA levels < .07 g/L) diagnosed in 1980-2010 in six university hospitals. In 1973-2010, these women delivered 1,172 singleton infants registered in the Swedish Medical Birth Register. Each delivery to a woman with IgA deficiency was matched on maternal age, parity, early pregnancy smoking status, education level, and delivery year with up to 5 control births ( n = 5,758). Results: Offspring to women with IgA deficiency had 79 g lower birth weight than controls (mean ± SD: 3,457 ± 559 vs 3,537 ± 553 g, P < 0.001), and 1.4 days shorter gestational age (mean ± SD: 278 ± 13 vs 280 ± 14 days, P = 0.001). No difference in preterm birth (<37 weeks) could be detected in deliveries to women with IgA deficiency vs control deliveries (5.8 % vs 5.2 %; odds ratio (OR) = 1.13, 95%CI = 0.85-1.49), but small for gestational age birth was more common (4.3 % vs 2.8 %; OR = 1.48, 95%CI = 1.04-2.10). Women with IgA deficiency also delivered more often by caesarean section (16.9 % vs 11.9 %; OR = 1.51, 95%CI = 1.26-1.82), while no difference was observed regarding low Apgar score (<7 at 5 min; 1.1 % vs 1.0 %; OR = 1.18; 95%CI = 0.62-2.27). When excluding women with autoimmune diseases, the excess risks of adverse pregnancy outcome diminished. Conclusion: There is a small excess risk of certain adverse delivery and perinatal outcomes among offspring to women with IgA deficiency. These excess risks are attenuated when considering the presence of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Purpose: To examine autoimmune disorders in patients with IgA deficiency compared with the general population. Methods: Nationwide prospective population-based cohort study. Through six university hospitals in Sweden we identified 2100 individuals with IgA deficiency (IgA levels < .07 g/L) diagnosed between 1980 and 2011. Each patient with IgA deficiency was matched on age, sex, place of residence, and year of diagnosis with up to 10 general population controls ( n = 18,653). Data on nine autoimmune disorders were retrieved from the Swedish National Patient Register (including inpatient and non-primary outpatient care). Autoimmune disorders were defined as having at least two visits listing the relevant international classification of disease (ICD) code as main diagnosis. Prevalences and prevalence ratios (PRs) were calculated. Results: Individuals with IgA deficiency more often had celiac disease (6.7 % vs. 0.19 % in controls) and type 1 diabetes (5.9 % vs. 0.57 %) corresponding to a 35-fold higher PR for celiac disease and 10-fold higher for type 1 diabetes. Also for the other autoimmune diseases did we see statistically significantly elevated prevalences and PRs (juvenile idiopathic arthritis (0.76 % vs. 0.09 % in controls, PR = 8.9), systemic lupus erythematosus (0.57 % vs. 0.06 %; PR = 8.9), inflammatory bowel disease (3.9 % vs. 0.81 %; PR = 5.0; specifically Crohn's disease (2.4 % vs. 0.42 %; PR = 5.7) and ulcerative colitis (1.7 % vs. 0.46 %; PR = 3.9)), hypothyreosis (0.76 % vs. 0.16 %; PR = 4.6), rheumatoid arthritis (2.2 % vs. 0.50 %; PR = 4.5), and hyperthyreosis (1.7 % vs. 0.43 %; PR = 3.9), but not with myasthenia gravis (0.05 % vs. 0.02 %; PR = 3.0). Conclusions: Individuals with IgA deficiency have a higher prevalence of several other autoimmune disorders. [ABSTRACT FROM AUTHOR]

Purpose: Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency with a prevalence of 1/600 in the general population. Any targeted health-related quality of life (HRQL) study of adults with SIgAD has never been presented. The objectives of the study were to compare HRQL between SIgAD adults and randomly selected age- and gender-matched population controls, and to identify risk factors for poor HRQL. Methods: Thirty-two SIgAD individuals and 63 controls answered three questionnaires (clinical data, Short Form-36 Health Survey (SF-36), infection-related HRQL) at baseline before undergoing medical/dental examinations and laboratory assessments. HRQL in SIgAD was re-evaluated after 6 and 12 months. Results: Baseline: Selective IgA deficiency individuals reported significantly increased fear of contracting infections ( p < 0.01). Those scoring high on fear also perceived significantly poorer physical health ( p < 0.01). SF-36 results indicated that SIgAD individuals perceived poorer HRQL, although this was not statistically significant. Follow-up: Compared with SF-36 responses at baseline, SIgAD individuals reported significantly more pain ( p < 0.01) at 6 months, poorer general health ( p < 0.05) and summarised physical HRQL ( p < 0.01) at 6 and 12 months and decreased vitality at 12 months. The summarised mental scale remained stable over time. Risk factors for poor HRQL: The number of antibiotic treatments during the previous year ( p < 0.001), number of daily medications ( p < 0.01), allergic rhinoconjunctivitis ( p < 0.05), chronic musculoskeletal symptoms at least every week ( p < 0.05) and anxiety and/or insomnia ( p < 0.05) were identified as independent risk factors for poor HRQL. Conclusion: The study highlights the importance of identifying and thoroughly evaluating, educating and following up individuals with SIgAD, as their HRQL may be negatively affected due to health problems possible to prevent and treat. [ABSTRACT FROM AUTHOR]

Purpose: Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians with a prevalence of 1:600. However, the prevalence of IgAD is markedly lower in East Asian countries but no genetic studies have been performed on IgAD individuals in the Mongoloid population. Methods: We investigated the prevalence of IgAD in a large number of Chinese blood donors ( n = 39,015) in Shanghai, China. We measured immunoglobulin class, IgG subclass and anti-IgA serum levels among the IgAD donors. These donors were subsequently tissue typed and the allele frequency was compared with the Shanghai bone marrow donor HLA registry. Results: Seventeen IgAD Chinese blood donors were identified, giving a prevalence of 1: 2,295. Two previously identified IgAD blood donor samples were added in the subsequent tests. Most IgAD donors had serum IgG levels above the normal range with no major IgG subclass deficiency and one donor was weakly positive for anti-IgA. Two-thirds of the Chinese IgAD donors carried Caucasian IgAD associated risk haplotypes, including DRB1*0301-DQB1*0201, DRB1*0701-DQB1*0202 and DRB1*0102-DQB1*0501, giving a significantly higher frequency of these haplotypes as compared to the Shanghai bone marrow donor HLA registry. Conclusions: The prevalence of IgAD in Chinese in this study is markedly lower than in Caucasians. This is the first study to investigate the genetics of IgAD in the Mongoloid population and two-thirds of the Chinese IgAD donors showed a mixture of Caucasian IgAD risk haplotypes. The low prevalence of IgAD could potentially be due to the low frequency of the disease associated risk haplotypes in China. [ABSTRACT FROM AUTHOR]

IgA deficiency has been linked to increased morbidity but data on mortality is lacking. In this population-based prospective cohort study we examined mortality in patients with IgA deficiency compared with the general population. Through six university hospitals in Sweden we identified 2,495 individuals with IgA deficiency (IgA deficiency≤0.07 mg/L) diagnosed between 1980 and 2012. Each patient with IgA deficiency was matched on age, sex, place of residence, and year of diagnosis with up to 10 general population controls ( n = 24,509). Data on education level and emigration status were obtained from Statistics Sweden. Our main outcome measure was all-cause mortality retrieved from the nationwide Causes of Death Register, which includes >99 % of all deaths in Sweden. We used Cox regression to estimate mortality hazard ratios conditioned on the matching factors and adjusted for education level. During 25,367 person-years of follow-up (median 8.3), there were 260 deaths in the IgA deficiency group versus 1,599 deaths during 257,219 person-years (median 8.6) in the general population controls (102 versus 62 deaths per 10,000 person-years; incidence rate difference, 40, 95%CI 28–53, P < . 001). This corresponded to a conditional mortality hazard ratio of 1.8 (95%CI 1.6–2.1, P < . 001). Relative mortality varied by follow-up time ( P < . 001) from a hazard ratio of 3.6 (95%CI 2.5–5.3; P < .001) during the first year to 1.9 (95%CI 1.5–2.4; P < .001) year 1–4; 1.9 (95%CI 1.4–2.4; P < .001) year 5–9; 1.5 (1.0–2.2; P = .054) year 10–14.9; and 1.1 (0.7–1.6; P = .66) year 15–25. Effect modification was also seen by age in each stratum of follow-up time, with higher relative mortality in younger than older patients ( P < . 001). In conclusion, patients with IgA deficiency are at increased risk of death in the first 10 to 15 years after diagnosis. [ABSTRACT FROM AUTHOR]

The immune system has evolved to respond to pathogens (nonself) and unresponsive to self-antigens (tolerance). During the development of T and B cells in the thymus and bone marrow, respectively, self-reactive T and B cells are deleted by a process of apoptosis (both T and B cells) and become unresponsive to self-antigen by receptor editing (for B cells). However, few self-reactive T cells are leaked into the periphery. A number of mechanisms are responsible to ensure that self-reactive T and B cells remain unresponsive to self-antigens. In the central tolerance, major mechanisms include apoptosis (for T cells) and receptor editing (for B cells), and in the peripheral tolerance, a major mechanism appears to be regulated by Treg cells. In T cell central tolerance, one of the most important molecules is a transcription factor, autoimmune regulator, which is selectively expressed in medullary thymic epithelial cells (mTECs) and constitutively regulates the transcription of hundreds of self-antigens in mTECs, thereby inducing central tolerance, negative selection, and Treg differentiation from some self-reactive thymocytes. Primary immunodeficiency diseases are a group of monogenic diseases where mutations of certain genes have resulted in the loss of central and/or peripheral tolerance. As a result autoimmunity and autoimmune diseases are common among patients with primary immunodeficiency diseases. Here, we have provided a comprehensive review of the mechanisms of central and peripheral tolerance and autoimmune manifestations and mechanisms of autoimmunity in primary immunodeficiency diseases. [ABSTRACT FROM AUTHOR]

Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency in Caucasians with a prevalence of 1/600 and is generally considered a mild disorder. In this study, the clinical status of 32 adults with SIgAD was investigated and compared to 63 age- and gender matched controls, randomly selected from a population database. The SIgAD individuals reported significantly more often contracting various upper and lower respiratory infections, with 8 (25.0 %) having been diagnosed with ≥1 pneumonia in the preceding two years, compared to one (1.6 %) control ( p < 0.001). Furthermore, the SIgAD individuals were found to have increased proneness to infections and increased prevalence of allergic diseases and autoimmunity, with a total of 84.4 % being affected by any of these diseases, compared to 47.6 % of the controls ( p < 0.01). This study challenges the common statement of SIgAD being a mild form of immunodeficiency. It also highlights the importance of using matched controls in PID clinical research to better detect clinically important manifestations. [ABSTRACT FROM AUTHOR]

Introduction: Selective deficiency IgA (IgAD) is the most common primary abnormality of immunoglobulin production with unknown pathophysiology. It is genetically related to common variable immunodeficiency (CVID), where besides IgA also IgG and frequently IgM serum levels are decreased. In this study we focused on determination of B-lymphocyte developmental stages and searching for similarities between CVID and IgAD. Materials and Methods: Using flow cytometry we determined major lymphocyte subpopulations and B-lymphocyte subsets: naïve (CD27IgD), marginal zone cells (CD27IgD), class-switched memory cells (CD27IgD), 'double-negative' B cells (CD27IgD), transitional cells (IgMCD38), plasmablasts (CD38IgM or IgM), and CD21CD38 cells in 80 patients with IgAD, 48 patients with CVID, and 80 control persons. Results: Compared to healthy controls, a decrease in the absolute number and frequency of CD4+ cells (both < 0.001) was observed in IgAD patients. A decrease in the frequency of switched memory cells ( P < 0.001), transitional cells ( P = 0.035) as well as plasmablasts ( P < 0.001) and an increase in the CD21CD38 subset ( P = 0.007) was observed in IgAD patients compared to control persons. No significant differences were observed in the remaining B-cell developmental subsets. A decrease in CD27IgD (<0.4% of peripheral blood lymphocytes), frequently observed in CVID patients and also previously reported in IgAD, was found in only five patients (6%) with IgAD, two of them being first-degree relatives of CVID patients. Conclusion: Our results show a decrease of terminally differentiated B-lymphocyte subsets in patients with IgAD, similar as previously found in patients with CVID, but these results are less expressed than in CVID patients. [ABSTRACT FROM AUTHOR]

An increased prevalence of immunoglobulin (Ig) A deficiency has been documented in a number of autoimmune diseases; however, its association with type 1 diabetes mellitus (DM1) is a subject of debate. This study was performed to evaluate serum IgA levels in a group of pediatric patients with DM1. Three hundred patients with mean age of 12.6 ± 6.7 years were enrolled in this study. Serum IgA and other immunoglobulins levels were measured using enzyme-linked immunosorbant assay. Mean serum IgA level of patients was 271.0 ± 141.4 mg/dl. Only two patients had IgA deficiency (IgA < 10 mg/dl), who were two boys with ages of 9 and 10 years. Although associated autoimmune disorders were found in a number of patients with DM1, no other autoimmune disorder was detected in these two patients with IgA deficiency. Serum levels of all other immunoglobulins were normal. Serum IgA levels did not significantly differ by grouping the patients according to age variation, sex distribution, disease duration, and associated disorders. There was no significant correlation between IgA levels and hemoglobin A1c. This study showed the prevalence of IgA deficiency in Iranian patients with DM1 as 0.7% (1:150), which is much higher than reported prevalences in general populations. Further studies are needed for better understanding the possible etiologies of increased IgA deficiency in DM1 and its effects on diabetes control. [ABSTRACT FROM AUTHOR]

Background: There have been few reports on children who developed common variable immunodeficiency (CVID) in association with immunoglobulin A (IgA) and IgG2 deficiencies and systemic lupus erythematosus (SLE). Case-Diagnosis/Treatment: Our patient experienced nephrotic syndrome and acute respiratory distress syndrome (ARDS) caused by influenza A/H1N1 virus infection at 5 years of age. A diagnosis of IgA and IgG2 deficiency and SLE was made on the basis of severe proteinuria, hematuria, hypocomplementemia, high anti-DNA antibody and antinuclear antibody (ANA) titers, and malar rash. However, these clinical signs and symptoms and laboratory features disappeared after the administration of methylprednisolone pulse therapy and prednisolone. For the 5 years following the initial treatment for SLE, the patient experienced a number of infections and had a low serum total IgG level; she was eventually diagnosed with CVID. The administration of intravenous immunoglobulin (IVIG) was required to prevent subsequent infections, and no relapse of SLE was observed. Conclusion: We report the development of CVID in an IgA- and IgG2-deficient patient with SLE on the basis of multiple episodes of infection. To prevent the development of CVID in IgA- and IgG2-deficient patients with SLE, it is important to prevent immune dysregulation by the avoidance of infections through the use of IVIG therapy. [ABSTRACT FROM AUTHOR]

Chronic arthritis may occur in association with antibody deficiency and chromosomal aberrations. This report presents the case of a 6-year-old girl with chromosome 22q11 deletion syndrome and chronic arthritis. The onset of arthritis occurred at 4 years of age. The chronic arthritis course has been the polyarticular type. Neither antinuclear antibody nor rheumatoid factor was detected. Serum IgA was extremely low. She was diagnosed with juvenile idiopathic polyarticular arthritis (JIA) complicated by IgA deficiency in the 22q11 deletion syndrome. There is an increased prevalence of chronic arthritis in association with 22q11 deletion syndrome with IgA deficiency, but the reasons for this association are unknown. This study evaluated the possible correlation between cytokines and the susceptibility to chronic arthritis in the 22q11 deletion syndrome with IgA deficiency. The expression of pro-inflammatory cytokines such as IL-8, IL-6, MIP-1β, and MCP-1 suggests that T and B cells, macrophages and neutrophils modulate joint inflammation by an immune response. And the presence of IL-10 and IL-5 might suggest that the synovitis is associated with JIA and IgA deficiency. [ABSTRACT FROM AUTHOR]

TNFRSF13B/TACI defects have recently been associated with common variable immunodeficiency (CVID) pathogenesis. Considering that TNFRSF13B/TACI is very polymorphic and the frequency of its alterations may be different in various ethnic groups, we analyzed their prevalence in 47 Greek patients with antibody deficiencies, including CVID (16 patients), IgAD (16 patients), selective IgG4D (11 patients), and transient hypogammaglobulinemia of infancy (4 patients). A rather high frequency of TNFRSF13B/TACI defects was identified in patients with selective IgG4D (18.18%). Moreover, a patient with CVID was heterozygous in the common C104R mutation (6.25%). Both his children and a further healthy individual carried the same mutation, albeit without recurrent infections and/or hypogammaglobulinemia. The common polymorphisms V220A and P251L were identified in all disease subgroups, in an almost similar frequency with that observed in 259 healthy controls. Our data provide further evidence that TNFRSF13B/TACI alterations are not causative of CVID. Possibly, they predispose to humoral deficiencies and/or contribute to their phenotype when combined with other immune gene alterations. [ABSTRACT FROM AUTHOR]

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA and IgG subclass deficiencies to the severe congenital agammaglobulinemias, in which the antibody production of all immunoglobulin isotypes is severely decreased. Apart from recurrent respiratory tract infections, PADs are associated with a wide range of other clinical complications. This review will describe the pathophysiology, diagnosis, and treatment of the different PADs. [ABSTRACT FROM AUTHOR]

We report a case of Henoch-Schönlein purpura nephritis (HSPN) with acquired IgA deficiency due to parvovirus B19 infection. The patient was diagnosed as having Henoch-Schönlein purpura (HSP) at 6 years old, and subsequently developed macrohematuria and massive proteinuria of 7.4 g/day with decreased creatinine clearance of 70.2 ml/min/1.73 m and significantly elevated serum IgA level of 449 mg/dl. The first kidney biopsy yielded the diagnosis of severe HSPN. After the initiation of the immunosuppressive therapy, the patient was infected with parvovirus B19 and developed virus-associated hemophagocytic syndrome (VAHS). Thereafter, the serum level of IgA selectively decreased and remained undetectable until the present time. Repeated kidney biopsies performed over a period of 14 years revealed a remarkable histological improvement in association with stabilization of the patient's kidney function. Considering the severity of initial kidney injury, persistent acquired IgA deficiency was likely to add favorable effects to the immunosuppressive therapy in this patient with HSPN. [ABSTRACT FROM AUTHOR]

IgA deficiency is the most common human primary immune-deficiency. We evaluated the clinical and immunological characteristics of selective IgA deficiency in children in Israel. The study group included 63 children diagnosed with IgA deficiency from 1987 to 2005. Mean follow-up time per child was 10.6 years. Average age at diagnosis was 10.5 years. In one child, the IgA deficiency was transient. Infectious diseases, mainly recurrent pneumonia and ear infection, were common and occurred in 25 patients (39.7%). Allergic diseases were documented in 20 (31.7%) of our patients. Thirteen children (20.6%) had autoimmune diseases. Malignancies were diagnosed in three children (4.8%), an association that has not been reported in previous series. IgA deficiency appears to be a risk factor for infections, allergic diseases, autoimmune conditions, and malignancy. [ABSTRACT FROM AUTHOR]

Selective IgA deficiency (IgAD; serum IgA concentration of <0.07 g/l) is the most common primary immunodeficiency in Caucasians with an estimated prevalence of 1/600. The frequency of the extended major histocompatibility complex haplotype HLA A1, B8, DR3, DQ2 (the “8.1” haplotype) is increased among patients with IgAD. We carried out a direct measurement of the relative risk of homozygosity of the 8.1 haplotype for IgA deficiency in a population-based sample of 117 B8, DR3 homozygous individuals. IgA deficiency was found to be present in 2 of 117 (1.7%) of these subjects, a figure that is concordant with estimates of relative risk from large case–control studies in the Swedish population. These data are consistent with a multiplicative model for the 8.1 haplotype contribution to IgA deficiency and contrasts with prior studies, suggesting a much higher risk for 8.1 homozygosity. Using a dense single nucleotide polymorphism marker analysis of the MHC region in HLA B8, DR3, DQ2 homozygous individuals, we did not observe consistent differences between cases ( n = 26) and controls ( n = 24). Overall, our results do not support the hypothesis that IgA deficiency is associated with a distinct subgroup of 8.1 related haplotypes, but rather indicate that risk is conferred by the common 8.1 haplotype acting in multiplicative manner. [ABSTRACT FROM AUTHOR]

A 42-year-old female with immunoglobulin A deficiency and recurrent sinopulmonary infections underwent thyroidectomy for papillary thyroid cancer (PTC). Follow-up I scintigraphy demonstrated diffuse pulmonary uptake, suggesting metastatic disease. However, subsequent pathologic, biochemical and radiographic testing proved that she was in fact disease free, and the initial I pulmonary uptake was identified as a false positive. Inflammatory conditions may rarely cause iodine uptake in non-thyroidal tissues due to local retention, organification, and/or immunologic utilization. To avoid exposing patients to unnecessary treatments, it is critical for clinicians to recognize that comorbid pulmonary conditions may mimic metastatic PTC on radioiodine scintigraphy. [ABSTRACT FROM AUTHOR]

There has been growing recognition of a changing clinical presentation of celiac disease (CD), with the manifestation of milder symptoms. Serologic testing is widely used to screen patients with suspected CD and populations at risk. The aim of this retrospective analysis was to evaluate the clinical presentation of CD in childhood, assess the diagnostic value of serologic tests, and investigate the impact of IgA deficiency on diagnostic accuracy. We evaluated 206 consecutive children with suspected CD on the basis of clinical symptoms and positive serology results. Ninety-four (46%) had biopsy-proven CD. The median age at diagnosis of CD was 6.8 years; 15% of the children were <2 years of age. There was a higher incidence of CD in girls (p = 0.003). Iron deficiency and intestinal complaints were more frequent in children with CD than those without CD (61% vs. 33%, p = 0.0001 and 71% vs. 55%, p = 0.02, respectively), while failure to thrive was less common (35% vs. 53%, p = 0.02). The sensitivity of IgA tissue transglutaminase (IgA-tTG) was 0.98 when including all children and 1.00 after excluding children with selective IgA deficiency. The specificity of IgA-tTG was 0.73 using the recommended cut-off value of 20 IU, and this improved to 0.94 when using a higher cut-off value of 100 IU. All children with CD and relative IgA deficiency (IgA levels that are measurable but below the age reference [n = 8]) had elevated IgA-tTG. In conclusion, CD is frequently diagnosed in school-age children with relatively mild symptoms. The absence of intestinal symptoms does not preclude the diagnosis of CD; many children with CD do not report intestinal symptoms. While the sensitivity of IgA-tTG is excellent, its specificity is insufficient for the diagnostic confirmation of a disease requiring life-long dietary restrictions. Children with negative IgA-tTG and decreased but measurable IgA values are unlikely to have CD. [ABSTRACT FROM AUTHOR]

Susceptibility to IgA deficiency (IgAD) is strongly associated with alleles of HLA, but it is not equally strong in different human populations. Therefore, the goal of this study was to determine the HLA-A,-B and-DRB1 antigenic and haplotypic frequencies in unrelated Polish Caucasian IgA-deficient patients who had never been examined so far in this respect. The HLA alleles were determined by means of low resolution polymerase chain reaction with sequence specific primers (PCR-SSP) method in a group of IgA-deficient patients and control subjects from the same area. The HLA-DRB1*03 allele showed the strongest association with IgA deficiency in the Polish population (OR=6.6, pcor=0.0084). The HLA-B*08 allele was also associated with predisposition to the disease (OR=6.22, pcor=0.033). These significant associations could be explained in the context of a positive association of IgAD with the HLA-B*08:DRB1*03 haplotype, previously reported in other Caucasoid populations from Northern and Central Europe. In our group the HLAB*08:DRB1*03 haplotype was present in 52.9% of IgA-deficient patients comparing to 9.9% in controls (p<0.00011). A positive association of HLA-B*08 and DRB1*03 was stronger in IgA-deficient males than in females from the same group. Immunoglobulin A deficiency in Polish population is strongly associated with HLA-B*08:DRB1*03 haplotype rather than with single alleles. [ABSTRACT FROM AUTHOR]

The phenotype of common variable immunodeficiency (CVID) is characterized by recurrent infections owing to hypogammaglobulinemia, with deficiency in immunoglobulin (Ig)G and at least one of IgA or IgM. Family studies have shown a genetic association between CVID and selective IgA deficiency (IgAD), the latter being a milder disorder compatible with normal health. Approximately 20–25% of CVID cases are familial, if one includes families with at least one case of CVID and one of IgAD. Nijenhuis et al described a five-generation family with six cases of CVID, five cases of IgAD, and three cases of dysgammaglobulinemia. We conducted a genome-wide scan on this family seeking genetic linkage. One interval on chromosome 4q gives a peak multipoint LOD score of 2.70 using a strict model that treats only the CVID patients and one obligate carrier with dysgammaglobulinemia as affected. Extending the definition of likely affected to include IgAD boosts the peak multipoint LOD score to 3.38. The linkage interval spans at least from D4S2361 to D4S1572. We extended our study to a collection of 32 families with at least one CVID case and a second case of either CVID or IgAD. We used the same dominant penetrance model and genotyped and analyzed nine markers on 4q. The 32 families have a peak multipoint LOD score under heterogeneity of 0.96 between markers D4S423 and D4S1572 within the suggested linkage interval of the first family, and an estimated proportion of linked families (α) of 0.32, supporting the existence of a disease-causing gene for autosomal-dominant CVID/IgAD on chromosome 4q.European Journal of Human Genetics (2006) 14, 867–875. doi:10.1038/sj.ejhg.5201634; published online 26 April 2006 [ABSTRACT FROM AUTHOR]

Objective: The term "IgA Deficiency (IgAD)" should be reserved for the individuals who do not have detectable disorders known to be associated with low IgA levels. IgG subclass deficiency or a lack of the IgG2 subclass that is specific against polysaccharide antigens, can be seen in many cases.Methods: Forty-five patients (27 males and 18 females; mean age 8.6 years, range 6.3 to 12.8 years) with IgA deficiency who had been admitted to the Department of Pediatric Immunology in Uludag University School of Medicine, Turkey, were included in this study. Serum immunoglobulin (Ig) class and IgG subclass levels, and HLA haplotypes were prospectively determined in patients and healthy controls.Results: Of the 45 patients with IgAD, 1 was found to have a low level of IgG in the serum. Serum Ig levels were also examined in the families of 22 patients. Five patients had low-normal levels of IgM, whilst one had low levels of IgA and IgG. The levels of IgG subclasses were assessed in 23 patients. One patient had a low level of IgG1; 2 had low levels of both IgG2 and IgG3, and 11 had low levels of IgG3. IgG subclass concentrations were found to be normal in control groups. HLA alleles were tested in 25 patients. An increased prevelence of HLA-A1, -B8, -B14, -DR1, -DR3, and -DR7 were previously observed in patients with IgA deficiency. In this study, HLA-A1 allel was found in 3 patients (12%), HLA-B14 in 3 patients (12%), HLA-DR1 in 10 patients (40%), HLA-DR7 in 4 patients (16%) and HLA-DR3 in 1 patient (4%). HLA-B8 allel was not found in any patient. Twenty-five children with normal IgA levels have chosen as a control group. They had HLA-DR1 (36%), HLA-DR7 (16%), HLA-B8 (8%), HLA-DR3 (16%). HLA-A1 was not found in any member of our control group.Conclusion: No statistically significant difference in HLA susceptibility alleles was found between patients and healthy controls. Our data suggest that there may be heterogenous HLA distribution patterns in IgA deficiency, or that HLA allel-associated tendency to IgA deficiency may be polygenic. [ABSTRACT FROM AUTHOR]

Both celiac disease and inflammatory bowel disease (IBD) are characterized by chronic diarrhea and the presence of distinct (auto)antibodies. In the present study we wanted to determine the prevalence of serological markers for inflammatory bowel disease, i.e., perinuclear antineutrophil cytoplasmic antibodies (pANCA) and/or anti- Saccharomyces cerevisiae antibodies (ASCA), in 37 patients with biopsy-confirmed celiac disease (Marsh IIIb/c). The majority of the patients was positive for IgA (auto)antibodies typically associated with celiac disease, i.e., antiendomysium antibodies (EMA) (86.5%), antigliadin antibodies (AGA) (73%), and antirecombinant human tissue transglutaminase antibodies (rh-tTGA) (86.5%). Four patients with selective IgA deficiency could be identified by analyzing EMA, AGA, and rh-tTGA for the IgG isotype. The prevalence of pANCA and ASCA, markers that are used for IBD, was unexpectedly high in our cohort of patients with celiac disease: 8 patients were positive for pANCA (IgG) and 16 patients were positive for ASCA (IgG and/or IgA). These results indicate that the presence of pANCA or ASCA in the serum of patients with chronic diarrhea does not exclude celiac disease. A prospective study is required to determine whether pANCA and/or ASCA identify patients at risk for developing secondary autoimmune disease. [ABSTRACT FROM AUTHOR]

Fifty children with IgA deficiency were folllowed for 1 to 4 years from 1975 to 1978. Thirty-five had complete deficiency of serum IgA (less than 2.5 IU/ml) and 15 partial deficiency (serum IgA below the 10th centile for age). Patients with another associated immunodeficiency, such as ataxia-telangiectasia, were not included. Most children with complete deficiency of IgA had recurrent respiratory and/or gastrointestinal infections, about half with onset in the first year of life, while partial deficiency of IgA has probably little if any importance for anti-infectious immunity but is important in the pathogenesis of atopy. Atopic diseases were frequent in both groups. Chromosomal abnormalities were found in 2 patients: trisomy 21 in one and in the other a ring chromosome 18. No important defects in cellular immunity were detected but some isolated, borderline abnormalities were often present. [ABSTRACT FROM AUTHOR]

The tissue types, immunoglobulin levels, and the presence of circulating autoantibodies were investigated in 57 children. Fifteen of these children suffered from bronchial asthma and, in addition, had no or very little IgA in their serum and saliva (Group 1 patients). Another fifteen children with asthma but normal immunoglobulin levels in serum and saliva (Group 2 patients), seven patients with selective IgA deficiency but without allergic diseases (Group 3 patients), and twenty healthy children served as controls. Sixty per cent of the Group 1 patients had the phenotype HLA-A1, B8, whereas this tissue type was found only in 27, 14 and 15 per cent, respectively, of the Group 2 and Group 3 patients and the healthy children. Furthermore, high IgM- and IgE levels were observed in most Group 1 patients, and in five of these patients (33 per cent) autoantibodies were present in the serum. In addition, eczema and glomerulonephritis occurred rather frequently in this group of patients. Conversely, normal immunoglobulin levels and absence of circulating autoantibodies were found in the remaining three groups of children. The results emphasize the heterogeneity of the IgA deficiency syndrome, and the question is raised as to whether the tissue type HLA-A1, B8 observed in most Group 1 patients reflects the abnormal immune reactivity of these patients. [ABSTRACT FROM AUTHOR]

Despite impressive recent advances in the understanding of the chemical and cellular bases of the reaginic response, the pathogenesis of atopic diseases still remains a matter of speculation. The frequent finding of atopic diseases in some primary immunodeficiencies such as selective IgA deficiency and the Wiskott-Aldrich syndrome offers a unique opportunity for studying the immune mechanisms underlying the genesis of atopy. Recent studies in subjects with selective IgA deficiency have challenged the well known hypothesis that atopy is the result of defective 'immune exclusion' by the secretory immune system. A number of immunological features found in the primary immunodeficiencies associated with atopic disorders suggest that defective homeostatic mechanisms regulating reaginic responses may play a major role in the pathogenesis of atopy. A thorough analysis of these disease combinations may help to generate new working hypotheses concerning the immune pathogenesis of atopic diseases. [ABSTRACT FROM AUTHOR]

A young woman presented with high fever and edema in January, 1984, and was diagnosed as having systemic lupus erythematosus. Prednisolone administration failed to improve her symptoms. In May she was admitted to hospital because of elevated erythrocyte sedimentation rate (ESR), hypoproteinemia, hypogammaglobulinemia, hypocomplementemia, positive antinuclear antibody, elevated immune complex level, and diarrhea. Edema disappeared following administration of diuretics and albumin, although the pathogenesis was still undetermined. In September, she was referred to our institution because of severe watery diarrhea and hypoproteinemia. Endoscopic examination showed a diffuse inflammatory lesion in the duodenum and the colon. Radioisotopic 51Cr-albumin study results were compatible with protein-losing enteropathy. Hypoproteinemia and inflammatory changes of the intestine were improved by antibiotics, suggesting that the inflammatory lesion was caused by bacterial infection. Despite the improvements in clinical symptoms and laboratory findings, the serum IgA level was still low and the thrombocytopenia remained. The morphological characteristics of the megakaryocytes were consistent with idiopathic thrombocytopenic purpura. In May, 1986, the thrombocytopenia deteriorated, causing purpura. Prednisolone was administered again, and this resulted in normalization of the platelet count, although the IgA level remained low. Finally the prednisolone was stopped, and the IgA level gradually recovered, with the improvement of the enterocolitis. The exact pathogenesis of the whole picture in this case is unclear, but an 8-year-long clinical course suggests that the protein-losing was caused by an infectious enterocolitis superimposed on IgA deficiency. [ABSTRACT FROM AUTHOR]

IgG1, IgG2, IgG3 and IgG4 serum concentrations were determined in 49 phenytoin-treated epileptic patients and in 19 untreated epileptic controls, using subclass-specific monoclonal antibodies in an ELISA technique. The IgG3 and IgG4 concentrations were significantly reduced in patients with IgA deficiency ( P<0.05, P<0.01 respectively). In contrast, IgG4 was elevated in the patients in whom phenytoin did not induce an IgA deficiency ( P<0.05). IgG1 and IgG2 concentrations did not differ in phenytoin-treated and untreated epileptic patients. IgG1, IgG2, IgG3 and IgG4 did not change after withdrawal of phenytoin. IgG subclass concentrations were not significantly correlated with frequency of respiratory tract infections. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Epidemiological studies have shown wide geographical and racial variations in the prevalence and pattern of immunodeficiency diseases. As there is no national registry, very little is known of the prevalence and nature of humoral immunodeficiency in the Arabian peninsula. We report here for the first time the analysis of serum immunoglobulin (Ig) levels in 2000 consecutive patients (age, 1–80 years). They were seen over a period of 6 years and were referred to us from six district hospitals for suspected immunodeficiency, autoimmunity, allergy, or immunoglobulin dyscrasia. Forty-six were found to be immunodeficient, in whom at least one of the Ig class was low; 15 had secondary immunodeficiency. The remaining 31 cases, representing 1.5% of the population studied (giving a prevalence of 1550/100,000 hospital registered patients), were categorized into four primary humoral immunodeficiency groups: these included, in order of frequency, (i) selective IgA deficiency (45%; 700/100,000) (ii) common variable immunodeficiency (CVID) (29%; 450/100,000), (iii) agammaglobulinemia (16%; 250/100,000), and (iv) selective IgG deficiency (10%; 150/100,000). Compared with similar hospital-based surveys in the west the prevalence of humoral immunodeficiency seems to be higher in Arabs; this in part may be related to race and higher rate of consanguinity. Most patients with IgA deficiency had either infection, atopy or autoimmunity. Compared with some other races, agammaglobulinemia (X- and non-X-linked) seems to be more prevalent. [ABSTRACT FROM AUTHOR]

Copyright of Immunologic Research is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A total of 210 patients with repeated infections were screened for IgG4 deficiency. In 30 patients (14%) IgG4 was undetectable by radial immunodiffusion (less than 30 mg/l). Of these patients 17 (57%) were less than 2 years of age. Concomitant IgA deficiency (IgA less than 0.05 g/l) was demonstrated in 11 cases (37%). IgG2 serum levels below the normal range were found in 26 children. IgG4 could be demonstrated at a concentration of 0.5-29 mg/l in all 30 patients using a more sensitive enzyme-linked immunosorbent assay technique. Although a highly selected group of patients was investigated, the percentage of individuals without detectable IgG4 by immunodiffusion was in the same range as reported in the literature for healthy control persons. It is thus concluded that IgG4 serum reference levels have to be defined using more sensitive methods and that the observed severe infections are more likely to be connected with low serum IgG2 and/or IgA levels than undetectable IgG4 as measured by immunodiffusion. [ABSTRACT FROM AUTHOR]

Selective IgA deficiency associated with glomerulonephritis is rare and no previous reports in childhood have been made of the association of IgA deficiency and membranous glomerulonephritis (MGN). We report a 5-year-old boy with selective IgA deficiency and MGN. He presented with nephrotic syndrome. Percutaneous renal needle biopsy showed diffuse global thickening on light microscopy and heavy IgG and moderate C3 deposits were found on immunofluorescence. Electron microscopy detected extensive global subepithelial deposition of electron-dense material with frequent intramembranous extension and spike formation. The pathological diagnosis was diffuse MGN stage 1. Oral prednisolone (1 mg kg-1 day-1), angiotensin-converting enzyme inhibitors (ACEI), and angiotensin II receptor blocker (ARB) were given resulting in reduction of proteinuria. The prednisolone dose was gradually tapered and discontinued after 2 months. At present the patient has been in complete remission for 10 months despite the discontinuance of prednisolone. In conclusion, our treatment with corticosteroid, ACEI and ARB reduced proteinuria and was effective for our case with selective IgA deficiency and MGN. [ABSTRACT FROM AUTHOR]

Previous studies in adult patients with selective IgA deficiency have pointed towards a possible connection between chombined IgA and alpha-1-antitrypsin deficiency and the development of bronchiectasis. Thus, investigation were conducted of serum alpha-1-antitrypsin levels and clinical symptoms in 48 children with selective IgA deficiency. However, alpha-1-antitrypsin deficiency was not found in this group of patients. Furthermore, radiographic signs of recurrent pneumonia restricted to certain fields of the lungs, suggestive of bronchiectasia, were not observed in the patients. Thus, although a highly selected group of children with selective IgA deficiency was studied, a connection between IgA deficiency and alpha-1-antitrypsin deficiency as not obvious. [ABSTRACT FROM AUTHOR]

No serum IgA was detected in a young male patient suffering from spondylarthropathy (SpA) with bilateral sacroiliitis arthritis, enthesopathy and inflammatory low back pain, whose symptoms occurred in reaction to a sexually induced urethritis. After a period of several months in which the spondylarthropathy was active, disease activity came to a rest. Three years later no progression of the SpA was observed. This finding might be an indication that IgA is not involved in the pathogenesis of spondylarthropathy. [ABSTRACT FROM AUTHOR]

The article presents a letter to the editor in response to the article "IgA Deficiency and Membranous Glomerulonephritis," by T. Watanabe published in the October 2005 issue.