Serum IgA Deficiency Research Articles

Antibody Responses After First and Second COVID-19 Vaccination in Patients With Chronic Lymphocytic Leukaemia

Background: B cell chronic lymphocytic leukaemia (CLL) is associated with immune suppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination.Methods: We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 13 patients underwent a standard interval (3-week) vaccine regimen whilst 286 underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. 267 samples were taken at 5 weeks after the first vaccine for patients on the extended interval regimen and 13 and 42 samples were taken at 2-4 weeks after the second vaccine in patients on the standard or extended vaccine regimens respectively.Findings: Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine, compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine.Interpretation: Antibody responses after both the first and second Covid-19 vaccine are lower in patients with CLL compared to age-matched donors. This is particularly marked in patients who are taking BTK inhibitors or have serum IgA deficiency. Further approaches such as repeat vaccination or administration of prophylactic antibody may be worthy of investigation for some patients. Funding Information: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.Declaration of Interests: None to declare. Ethics Approval Statement: The work was performed under the CIA UPH IRAS approval (REC 20\NW\0240) and conducted according to the Declaration of Helsinki and good clinical practice. Ethical approval was obtained from North West Preston Research Ethics Committee with favourable outcome. Informed consent was obtained in person or by remote consultation.

Celiac disease in children with Down syndrome.

Celiac disease (CD) in children with Down syndrome (DS) has been published by several countries, without available data for Colombia. To determine the frequency and related factors of CD in children with DS, compared with a group of children without DS, analyzing the clinical, im munological, and genetic manifestations. A total of 209 children between 1-18 years of age (8.4 ± 4.1 years, 55.5% female) were studied, 97 with DS and 112 without DS, using anti-transglutaminase antibodies as serological marker (tTG2). Variables of age, gender, race, ori gin, weight, height, and digestive symptoms were studied. Children with positive tTG2 underwent duodenal biopsy and genotype. The proportion of children with DS, without DS, and CD was esti mated and their 95% CI; measures of central tendency, univariate and bivariate analysis, considering a p < 0.05 significant. Eight children with DS (8.2%) and five children without DS (4.5%) were tTG2 positive (p = 0.200). None presented serum IgA deficiency. One child with DS presented CD with Marsh II (1.0%), and two children with DS (2.1%) and two without DS (1.8%), presen ted potential CD (p = 0.432). Three children were HLA-DQ2. CD was more likely in the preschool group (OR = 6.14 95%CI = 0.41-87.35 p = 0.0462). The CD frequency due to intestinal biopsy in children with DS is much lower than that reported in the literature, being associated with preschool, and having DQ2 as its main allele. These findings are similar to those described worldwide.

Development of highly sensitive IgA immunosensors based on co-electropolymerized L-DOPA/dopamine carbon nano-onion modified electrodes

The development of versatile platforms to construct novel and sensitive immunosensors is nowadays an intense research field. Nanomaterials and polymers are often combined to fabricate new platforms to immobilize capture antibodies. Here we evaluate for the first time the co-electropolymerization of dopamine (DA) and L-3,4-dihydroxyphenylalanine (L-DOPA) on carbon nano-onion (CNO) modified electrodes as versatile platform to develop electrochemical immunosensors. Mixtures of DA and L-DOPA at different molar rations were co-electropolymerized on CNO-modified glassy carbon electrodes to form a poly(L-DOPA/DA) film. Immobilization of aminoferrocene was used to estimate the number of accessible carboxylic acid groups on the surface (11.3 nmol/cm2), a value comparable to three-dimensional matrices. This platform was applied to the electrochemical detection of IgA antibodies using both a HRP-based sandwich type assay and label-free detection based on [Fe(CN)6]3-/4- signal blocking. The sandwich and the label-free assays showed a wide linear response with LOD of 19 and 48 ng/mL, respectively, allowing the detection of serum IgA deficiency. Most remarkably, the incorporation of CNO layer led to a significant improvement (three-orders of magnitude) of the analytical performance of these immunosensors due to a combination of high surface area and increased electron transfer rates provided by the CNO layer.

Ulcerative jejunitis in a child with celiac disease

BackgroundCeliac disease can present in children and adults with a variety of manifestations including a rare complication known as ulcerative jejunitis. The latter has been associated with refractory celiac disease in adult onset patients. The objective of this case report is to describe the first pediatric case of ulcerative jejunitis in celiac disease, diagnosed by capsule endoscopy, which was not associated with refractory celiac disease.Case presentationThe 9 year old girl presented with a history of abdominal pain and vomiting. Laboratory investigations revealed a slightly elevated IgA tissue transglutaminase antibody level in the setting of serum IgA deficiency. Initial upper endoscopy with biopsies was not conclusive for celiac disease. Further investigations included positive IgA anti-endomysium antibody, and positive HLA DQ2 typing. Video capsule endoscopy showed delayed appearance of villi until the proximal to mid jejunum and jejunal mucosal ulcerations. Push enteroscopy with biopsies subsequently confirmed the diagnosis of celiac disease and ulcerative jejunitis. Immunohistochemical studies of the intraepithelial lymphocytes and PCR amplification revealed surface expression of CD3 and CD8 and oligoclonal T cell populations. A repeat capsule study and upper endoscopy, 1 year and 4 years following a strict gluten free diet showed endoscopic and histological normalization of the small bowel.ConclusionUlcerative jejunitis in association with celiac disease has never previously been described in children. Capsule endoscopy was essential to both the diagnosis of celiac disease and its associated ulcerative jejunitis. The repeat capsule endoscopy findings, one year following institution of a gluten free diet, also suggest that ulcerative jejunitis is not always associated with refractory celiac disease and does not necessarily dictate a poor outcome.

354: Serum IgA Deficiency Is Common in Lung Transplantation and Is Independently Associated with Bronchiolitis Obliterans Syndrome (BOS)

354: Serum IgA Deficiency Is Common in Lung Transplantation and Is Independently Associated with Bronchiolitis Obliterans Syndrome (BOS)

Immunoglobulin concentrations in first-degree relatives of epileptic patients with drug-induced IgA deficiency.

Serum immunoglobulins A, G and M were studied in parents and siblings of 16 patients being treated for epilepsy. Five healthy families served as controls. Seven of the patients were low IgA-responders and the rest of the patients had shown normal IgA-levels during treatment. None of the parents and siblings studied showed a serum-IgA deficiency, with the exception of one mother who was being treated for rheumatoid arthritis with naproxen. Low serum concentrations of IgG and IgM were not found. A significantly increased IgM-level was found in first-degree relatives of the low IgA-responders, and the siblings of low 2gA-responders had significantly raised IgA in their sera.

Subclass composition and J-chain expression of the‘compensatory’ gastrointestinal IgG cell population in selective IgA deficiency

The subclass distribution of IgG-producing immunocytes was examined by two-colour immunohistochemistry in gastrointestinal mucosa of 14 patients with selective serum IgA deficiency providing the following biopsy material: gastric (n = 1); jejunal (n = 12); colonic (n = 1); and rectal (n = 2). All except two patients suffered from various infections, and coeliac disease was observed in six of them. Control reference data were based on biopsies from immunologically intact subjects, including histologically normal jejunal (n = 10) and large bowel (n = 10) mucosa and stomach mucosa with slight chronic gastritis (n = 8). The total mucosal population of immunoglobulin-producing cells per 500 microns gut length unit was only slightly decreased in IgA deficiency because of an increased number of IgG (30%) and especially IgM (71%) immunocytes. The IgG1 immunocyte proportion in the proximal gut (median 87%) was higher than that in the comparable controls (gastric 69%, jejunal 66%). A similar trend was seen in the distal gut (69%) compared with controls from the large bowel mucosa (55%). Conversely, IgG2 and IgG3 cell proportions were significantly decreased compared with the respective controls from the proximal gut. The same was true for IgG4, which also was significantly reduced in jejunal mucosa. Paired staining for cytoplasmic J chain and immunoglobulin isotype showed 71% positivity for jejunal IgG-producing cells in IgA deficiency, which was somewhat reduced compared with comparable controls (89%). J chain appeared to be preferentially expressed by IgG1 cells (75%), but was also found in IgG2 (70%), IgG3 (32%) and IgG4 cells (33%). IgM-producing cells showed a J-chain positivity (99%) in IgA deficiency similar to normal (100%). Our results suggested that the block in mucosal B cell differentiation to IgA expression in the proximal gut is mainly located immediately upstream to the CH alpha 1 gene, giving excessive terminal maturation of J-chain-positive IgG1 immunocytes.

P0415 PREVALENCE OF SERUM IGA DEFICIENCY AND CELIAC DISEASE: A CROSS-SECTIONAL STUDY IN 7.293 CAUCASIANS

Introduction: The frequency of serum IgA deficiency (SIgAD) differs between populations. SIgAD is known to be associated with celiac disease (CD) with an higher incidence than in the general population. Methods: In a serological CD-screening we used IgA EMA as the basic diagnostic test, thus also determining SIgA levels. Blood samples were taken from 4468 blood donors (group I; f:2265, m:2003) and 3028 male adolescents drafted for military service (group II) aged 30±14.2 yrs. (mean±SD). SIgAD and subnormal SIgA levels were defined by SIgA <0.07 g/L, and 0.07–0.7 g/L, resp. Means were compared by analysis of variance (ANOVA) and covariance (ANCOVA), frequencies by chi2 test. Subjects with positive IgA EMA or SIgAD were invited to further clinical investigations including duodenal biopsy. Results: 21 subjects had positive IgA EMA (0.28%; f:7, m, I:3, II:11), 17 of them underwent duodenal biopsy, in 13/17 subjects (76.5%; f:3, m, I:2, II:8) duodenal villous atrophy was diagnosed. The prevalence of CD (known CD and newly diagnosed CD)in group II was 1:190. 15 subjects (0.21%; f:1, m, I:14) had SIgAD; all had histologically normal mucosa. Subnormal SIgA levels were found in 155 persons (2.13%; f:21 [0.93% of the females]; m:134 [2.66% of the males; difference: 1.74%; 95% CI: 1.12–2.33%; p <0.001]). 3 of the males (group II) had positive IgA EMA; 2/3 had duodenal villous atrophy. Males were more likely to have subnormal SIgA levels or SIgAD (OR 3.09, 95% CI: 1.97–4.85). The prevalence of SIgAD and subnormal SIgA was lowest in winter (chi2 = 4.8; p = 0.002 [3 d.f] and chi2 = 43.2; p <0.001 [3 d.f.], resp.). SIgA levels were significantly higher during winter and increased with age, on average by 0.2 ± 0.06 g/L per decade of life (p <0.001). Taking into account the influence of age, SIgA levels were lower in females compared to males. Conclusion: 1) For group II, this screening revealed a significant increase of CD prevalence compared to previous analysis (1:190 vs. 1:380), with 2 of the newly diagnosed subjects having subnormal SIgA. 2) The prevalence of SIgAD and subnormal SIgA levels is higher in males. 3) There is also a significant influence of age and seasons on SIgA levels. These findings should be considered when using IgA-based antibody tests for CD screening.

P0435 CELIAC DISEASE, PRETERM AND SMALL FOR DATE BABY: IS THERE AN INCREASED RISK?

Introduction: Untreated celiac disease may adversely affect the reproductive system at different ages. Whether unrecognised celiac disease is a risk factor of preterm delivery is still uncompletely recognised. The role of paternal celiac disease is even more controversial. The aim of this study was to determine the prevalence of celiac disease in both parents of preterm or small for date newborns. Methods: Since May 2003 we consecutively enrolled 380 parents of preterm (<37° week)or small for date (<10°) babies born in 13 different neonatal centers (PremaCel Group) of Nord Italy. Total serum IgA (Roche Diagnostics, Milano) and human transglutaminase (Eu-tTG IgA, Eurospital, Trieste)were measured in all subjects. We considered as pathological values <4 mg/dl and >7 UA/ml, respectively. No exclusion criteria of enrollment was applied. Results: Two parents (1 father and 1 mother) showed pathological transglutaminase; another parent present serum IgA deficiency. The prevalence of celiac disease in our population was 1:190, similar to general adult Italian population. The compliance to the study was 98.8% of parents. Conclusion: Our preliminary data do not show an increased prevalence of celiac disease in parents of preterm or small for date newborns compared to reported Italian population.

Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians.

The frequency of serum IgA deficiency (SIgAD) differs between populations. We examined the prevalence of SIgAD in healthy Caucasians. Serum immunoglobulin A (SIgA) was measured in 7293 volunteers (2264 women, 5029 men) aged 30 +/- 14.2 years (mean +/- SD; range: 12-66). Serum immunoglobulin A and subnormal SIgA levels were defined by a SIgA level < 0.07 g L(-1), and between 0.07 and 0.7 g L(-1), respectively. Means were compared by analysis of variance (anova) and analysis of covariance (ancova); frequencies by the chi(2) test. Fifteen subjects (0.21%; one woman, 14 men) had SIgAD. Subnormal SIgA levels were found in 155 persons (2.13%): 21 females (0.93% of the females) and 134 males (2.66% of the males; difference: 1.74%; 95% CI: 1.12-2.33%; P < 0.001). Males were more likely to have subnormal SIgA levels or SIgAD (odds ratio 3.09, 95% CI: 1.97-4.85). The prevalence of SIgAD and subnormal SIgA was lowest in winter (chi(2) = 14.8; P = 0.002; 3 d.f.; and chi(2) = 43.2; P < 0.001; 3 d.f., respectively). Serum immunoglobulin A concentrations were significantly higher during winter. Serum immunoglobulin A levels increased with age on average by 0.2 +/- 0.06 g L(-1) per decade of life (P < 0.001). Taking into account the influence of age, SIgA concentration was lower in females as compared with males. The prevalence of SIgAD and subnormal SIgA levels is increased in males. There exists a significant influence of gender, age and seasons on SIgA levels.

Family members of patients with selective IgA deficiency should be routinely screened for primary immunodeficiency

Rationale Although the pathogenesis of selective IgA deficiency (SIgAD) is poorly understood, inheritance patterns suggest it is autosomal dominant. Despite this fact, first-degree family members of patients diagnosed with SIgAD are not routinely screened for primary immunodeficiency, due in part to lack of symptomatology. We wish to present a case in which two asymptomatic adult children of a 45 year old white female with SIgAD were screened and found to have both IgA deficiency and anti-IgA antibodies. Methods Bloodwork was first performed on the mother, and later on her children, and consisted of quantitative total serum Ig levels (IgM, IgG, IgA), serum IgE, IgG subtypes, anti-IgA antibody levels, humoral immune panel (diphtheria antitoxoid antibody, tetanus antitoxoid antibody, and a 6 serotype pneumococcal antibody panel), and a CBC with WBC count differential. Results The mother's bloodwork revealed a total serum IgA level of <13mg/dL (normal 81 to 463mg/dL). Her son, age 20, had an IgA level of <14mg/dL with a borderline low IgM level of 39mg/dL (normal 48 to 271mg/dL), and her daughter, age 22, had an IgA level of 33mg/dL, suggesting a relative deficiency of serum IgA. Additionally, each child had detectable anti-IgA antibodies of the IgG isotype. All other remaining lab results were unremarkable. Conclusions In order to decrease the morbidity and mortality of patients with SIgAD and/or carriers of anti-IgA antibodies, first-degree family members of individuals diagnosed with SIgAD should be routinely screened for primary immunodeficiency, regardless of their level of symptomatology.

Increased mucosal synthesis of rheumatoid factor (RF) in coeliac disease.

Increased serum levels of RF have been reported in patients with gluten sensitivity. The objective of this study was to investigate the in vivo secretion of different isotypes of RF in the small bowel in coeliac disease. Nineteen patients were investigated by perfusion of a defined jejunal segment, and the jejunal perfusion fluid was analysed for the presence of IgA and IgM anti-Fc (IgG). Five of the patients studied had serum IgA deficiency. Patients with partial/subtotal villous atrophy but no IgA deficiency (n = 7) had a four-fold increase of IgM-RF (P < 0.001) and a three-fold increase of IgA-RF (P < 0.001) compared with healthy controls (n = 29). Patients with normal jejunal mucosa but no IgA deficiency (n = 7) had similar IgA-RF and IgM-RF concentrations to healthy controls. Patients with serum IgA deficiency had no IgA-RF detectable in jejunal fluid but the highest IgM-RF concentrations, in particular in active disease. The coeliac patients had serum levels of IgA-RF and IgM-RF within the reference ranges. Jejunal fluid levels of IgA-RF and IgA-anti-gliadin antibodies were significantly correlated (P < 0.001). The data indicate that enhanced jejunal mucosal production of RF occurs above all in active coeliac disease. The findings suggest that the immune response to gluten induces a mucosal RF synthesis.

Anti-tissue transglutaminase antibodies in IgA deficient sera: might a proper cut-off value be of help in avoiding total serum IgA testing?

Background: The introduction of an ELISA for antibodies to tissue transglutaminase has opened an new era in the diagnosis of coeliac disease by offering a simple, reliable and observer non-dependent method for the identification of coeliac patients. Despite its high sensitivity and specificity, false negative results can be achieved if a total serum IgA deficiency occurs. IgA deficient sera need to be tested to assess the level of total serum IgA to exclude possible false negative results.Aim: The aim of this study was to evaluate whether it is possible to define a cut-off value for an anti tissue transglutaminase ELISA which could indicate total IgA deficiency. In such patients further IgA isotype testing would only be necessary.Methods: 75 sera from patients with total IgA serum deficiency (<0.05 g/L), 21 patients with low IgA levels (<0.16 g/L) were tested by means of an ELISA method for the detection of anti-tissue transglutaminase antibodies (Eu-tTG®IgA, Eurospital, Italy). Five patients (including 2 subjects affected by coeliac disease) with normal IgA values (>0.2 g/L) were used as controls.Results: Total IgA deficient sera: 75/75 sera gave anti TGA values <0.2 AU/ml Low serum IgA values: 19/21 sera gave TGA values below 1 AU/ml All the normal serum IgA sera gave values above 1 AU/ml. The CD patients had values of 14.1 and 14.6 AU/ml respectively.Conclusion: These results are preliminary data and need to be confirmed by means of additional data. However, total serum IgA deficient sera did not show Eu-tTG® IgA values above 1 AU/ml.The use of a cut-off value at 1 AU/ml might be useful in deciding whether to perform total IgA serum determinations in those patients whose serum TGA values are lower than 1 AU/ml.

TGF-β Receptor Controls B Cell Responsiveness and Induction of IgA In Vivo

To determine the role of the pleiotropic cytokine TGF-β in B cells, we generated mice lacking the TGF-β receptor (TβR) type II selectively in this cell type through conditional mutagenesis (Cre/loxP). The absence of TβRII in B cells leads to a reduced life span of conventional B cells, expansion of peritoneal B-1 cells, B cell hyperplasia in Peyer's patches, elevated serum immunoglobulin, and substantial IgG3 responses to a normally weak immunogen. This B cell hyperresponsiveness is associated with a virtually complete serum IgA deficiency. The data reveal differential roles of TβR in homeostasis and antigen responsiveness of B cell subpopulations and establish a critical function of the TGF-β receptor ligand pair in the induction of IgA responses in vivo.

Long-term follow-up of health in blood donors with primary selective IgA deficiency.

A 20-year health follow-up study of 159 initially healthy blood donors with a severe deficiency of serum IgA ( < 0.05 x 10(-3) g/L) and of 45 donors with decreased serum IgA (0.05 x 10(-3)-0.8 g/L) was carried out. The findings indicate that persons with a severe deficiency of and decreased serum IgA who are healthy as young adults have an increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age. Vitiligo, autoimmune hypothyreosis, milk intolerance, and possible rheumatoid arthritis were associated with severe IgA deficiency, but otherwise different degrees of IgA deficiency seem to be similar with respect to the appearance of diseases. Regardless of the fact that a total of 163 (80%) of the 204 IgA-deficient subjects had-episodes of infections, drug allergy, or autoimmune or atopic disease, the finding of primary, selective IgA deficiency in a healthy adult per se does not seem to predict severe life-threatening illnesses at least during 20 years of life.

Reduced Serum Level of Transforming Growth Factor-β in Patients with IgA Deficiency

Seventeen patients with IgA deficiency, 13 subjects with selective IgA deficiency and 4 with a combined IgA and IgG2 deficiency, were assessed for serum levels of cytokines relevant for B cell differentiation. Transforming growth factor (TGF)-β was quantified by bioassay and interleukin (IL)-4, IL-6, and IL-7 by immunoassay. The serum levels of TGF-β were significantly lower in patients with IgA deficiency than in healthy blood donors. Of the patients with IgA deficiency, 4 had detectable IL-4 levels while 4 of the others had detectable IL-6 levels in serum. IL-4 and IL-6 were not detected in the controls. Serum IL-7 levels were similar in patients and controls. A significant, negative correlation was found between serum TGF-β and the number of circulating B lymphocytes in the patients with IgA deficiency. No association was found between serum cytokine levels and the occurrence of infections at the time of study. Since TGF-β has been implicated in IgA isotype switching in man, and our study demonstrates an association between low serum TGF-β levels and IgA deficiency, dysregulation of TGF-β might be a contributing factor in the pathogenesis of IgA deficiency.

Long-term follow-up of anti-IgA antibodies in healthy IgA-deficient adults.

A follow-up study of anti-IgA antibodies in 159 healthy blood donors with severe deficiency of serum IgA (< 0.05 mg/L) and in 45 donors with decreased serum IgA levels (0.05-799 mg/L), identified in 1971-1980, was carried out. Initially anti-IgA antibodies were determined by a hemagglutination (HA) method and two reexaminations were done in 1990-1992 by an enzyme immunoassay. The median follow-up period was 19 years, during which anti-IgA level was changed considerably in only four persons, increased in two, and high level antibodies (> 1/1000 by HA) appeared in two. In reexaminations anti-IgA antibodies were found in 30 (19%) subjects with severe IgA deficiency and the antibody levels remained relatively constant in those who had high and medium antibody levels. Anti-IgA antibodies were not found in subjects with decreased, but detectable serum IgA. Thus it seems that only those healthy adults who have severe IgA deficiency develop anti-IgA antibodies and their anti-IgA levels remain fairly constant. Of the 159 subjects with severe IgA deficiency, 66 had a history of IgA exposure, but no correlation to anti-IgA development was noted.

The association of IgA deficiency but not IgG or IgM deficiency with a reduced patient and graft survival following liver transplantation.

Recipients of solid organ allografts require lifelong immunosuppression in order to prevent graft rejection and to maintain graft function. In general, such immunosuppression greatly impairs the cellular immune system, as this level of the immune system is principally responsible for self and non-self recognition. The consequences of allograft transplantation in terms of patient and graft survival when transplants are given to individuals who have a preexisting humoral immune deficiency characterized by a deficiency of the serum levels of one or more of the major Ig classes have not yet been reported. From February 1, 1981 through December 31, 1990, a total of 43 adult patients with a deficiency of 1 or more Ig classes received a ABO-matched liver allograft at this institution. This sample represents 2.5% of a total of 1684 adults transplanted during this interval. These 43 liver graft recipients could be divided into 3 major groups based upon the presence of an IgG, IgM, or IgA deficiency. IgG deficiencies were defined as levels less than 50 mg/dl. Patient and graft survival for the IgA-deficient group was significantly reduced (P less than 0.04 and P less than 0.009, respectively) compared with both the IgG- and IgM-deficient groups. The latter two groups did not differ from controls without an Ig deficiency for these same two endpoints. The major causes of death in the IgA-deficient group were sepsis and opportunistic infection. A third of the deaths in the IgA-deficient group occurred in the perioperative period (first 30 days) while greater than 50% of the deaths occurred within the first 3 months, and all deaths occurred before the first year. Based upon these data, the following conclusions can be made: (1) serum IgA deficiency but not IgG or IgM deficiency is associated with an increased post-OLTx death and graft loss rate; (2) the majority of these deaths are due to sepsis or an opportunistic infection; and (3) most of the deaths occur early. These data suggest that recognition of a deficiency of IgA prior to organ grafting necessitates meticulous attention to the prevention of infection in the immediate perioperative period if patient and graft survival of these patients is to be improved.

Jejunal secretion of secretory immunoglobulins and gliadin antibodies in celiac disease

The aim of this study was to determine the secretion of secretory immunoglobulins and gliadin antibodies in the small bowel in celiac disease. Twenty-four patients were investigated by perfusion of a defined jejunal segment. Four of the patients studied had a serum IgA deficiency and had no measurable amounts of secretory IgA in the perfusion fluid. The other patients demonstrated a significant increase in the jejunal concentration of secretory IgA (median 28.5 mg/liter) compared with healthy controls (median 16 mg/liter, N = 16) and of IgM, celiac (median 12.3 mg/liter) compared to healthy controls (median 6.8 mg/liter, N = 16). Jejunal IgA gliadin antibodies were detected in all patients except those with an IgA deficiency. All patients had jejunal IgM gliadin antibodies, but none of the patients had measurable jejunal IgG gliadin antibodies. A positive correlation was detected between serum and jejunal IgA gliadin antibody levels in the celiac patients, (P less than 0.01). Calculation of the ratio between gliadin antibodies and total levels of IgA and IgM in serum and jejunal perfusate demonstrated that the jejunal synthesis of gliadin antibodies of IgA and IgM type is both more pronounced and persistent than the systemic humoral immune response to gliadin.

Fc receptor function and circulating immune complexes in gluten sensitive enteropathy--possible significance of serum IgA.

The capacity to clear IgG containing immune complexes from the circulation was studied in patients with coeliac disease (n = 13), dermatitis herpetiformis (n = 8), and coeliac disease with concomitant serum IgA deficiency (n = 4). A small group of patients with active ulcerative colitis (n = 4) was included as a bowel disease control group. Clearance was estimated by measuring the disappearance rate of a bolus dose of intravenously injected IgG coated autologous erythrocytes. The mean T1/2 of clearance was prolonged in both coeliac disease (86 (24) minutes) and dermatitis herpetiformis (111 (35) minutes), compared with healthy subjects (20 (5) minutes) and coeliac patients with concomitant serum IgA deficiency (T1/2 = 17 (6) minutes). Patients with ulcerative colitis had a prolonged clearance, with a T1/2 of 195 (63) minutes. Values of circulating immune complexes were measured by four assays; C1q binding and C3, IgG, and IgA containing immune complexes. C1q binding immune complexes were detected only in IgA deficient gluten sensitive enteropathy. Patients with coeliac disease and dermatitis herpetiformis had higher values of C3, IgG, and IgA containing immune complexes than control subjects and serum IgA deficient patients with coeliac disease. The clearance rate was inversely correlated to the amount of immune complexes for the subgroups of gluten sensitive enteropathy.