Selective IgA deficiency and Crohn's disease: report of two cases.

Two patients are described with Crohn's disease and selective IgA deficiency. Serum IgA was undetectable in each case, and immunoperoxidase studies of the lamina propria showed a gross diminution of IgA-bearing plasma cells. Peripheral blood lymphocytes, however, showed normal numbers of IgA-bearing lymphocytes. The typical clinical course and histology in these two patients suggest that IgA-mediated responses in the mucosa are not involved in the pathogenesis of Crohn's disease.     

Selective IgA deficiency and spondyloarthropathy: a distinct disease?

A woman with selective IgA deficiency and severe ankylosing spondylitis (AS), complicated by intractable peripheral arthritis, is described. Three previous cases of selective IgA deficiency and AS have been reported, all of whom had severe AS. It is suggested that selective IgA deficiency is a poor prognostic factor in AS and therefore warrants further investigation to determine the clinical course of such patients.     

Selective IgA deficiency associated with glomerulonephritis and oligoarthritis.

A 59 year old woman with selective IgA deficiency associated with oligoarthritis and glomerulonephritis is described. She was seropositive for rheumatoid factor and renal histological examination showed a focal glomerulonephritis. High titre rheumatoid factor and a focal glomerulonephritis were also present in the only other well documented report of selective IgA deficiency and renal disease. Histological examination of the kidney suggested that the glomerulonephritis was mediated by immune complexes.     

Selective immune deficiency in IgA. Intestinal malabsorption syndrome and mixed connective tissue disease

We report the case of a 22-year old unmarried woman who presented with selective IgA immune deficiency, moderate intestinal malabsorption syndrome with pseudo-atrophy of the villi, and mixed connective tissue disease. Although immune deficiency and malabsorption syndrome are frequently associated, association with an autoimmune disease is rare and we were unable to find any case of association with a connective tissue disease in the literature.     

IgA deficiency and autoimmune hemolytic disease.

A case of familial selective IgA deficiency associated with autoimmune hemolytic disease is reported that illustrates the therapeutic implications when these two entities coexist. Immunoglobulin screening is recommended for patients with AHD who require blood transfusions, in order to identify IgA-deficient patients who may have anti-IgA anaphylactic reactions.     

IgA antibodies to gliadin and coeliac disease in psoriatic arthritis.

OBJECTIVES: To find out whether patients with psoriatic arthritis (PsoA) have an increased prevalence of antibodies to gliadin (AGA) and of coeliac disease. METHODS: One hundred and fourteen PsoA patients with skin disease of 20+/-13 yr and joint disease of 11+/-10 yr duration answered a questionnaire concerning their medical history and underwent clinical examination, including radiology. Serum IgA AGA and IgG AGA, IgA antibodies to endomysium and immunoglobulins, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration were determined. RESULTS: Five of the 114 patients (4.4%) had coeliac disease. After exclusion of these five patients, the mean IgA AGA concentration was significantly higher (P=0.0005) than that in a reference group. None of the patients had IgA antibodies to endomysium. The mean serum IgA concentration was significantly increased and IgM decreased. Patients with a high concentration of IgA AGA had significantly higher ESR and CRP and a longer duration of morning stiffness than those with a low AGA concentration. CONCLUSIONS: Patients with PsoA have an increased prevalence of raised serum IgA AGA and of coeliac disease. Patients with raised IgA AGA seem to have more pronounced inflammation than those with a low IgA AGA concentration.     

Linear IgA dermatosis, coeliac disease, and extraintestinal B cell lymphoma.

Linear IgA dermatosis is a malignancy associated rare bullous disorder similar to dermatitis herpetiformis. Linear IgA dermatosis differs from dermatitis herpetiformis in that the IgA deposits in the epidermal basement membrane are linear rather than granular. A patient is presented with coeliac disease who presented with linear IgA dermatosis and anaemia caused by chronic low grade B cell lymphoma.     

Mucosal secretory IgA and secretory piece in adult coeliac disease

Immunofluorescence studies with specific antisera to secretory IgA (11S IgA) and secretory piece were carried out on the jejunal mucosa of nine patients with adult coeliac disease (treated and untreated). The results were compared with those obtained in four normal patients and in four patients with local and systemic IgA (7S) deficiency. 11S IgA and secretory piece were localized to the upper third of the epithelial cells of both surface and glandular epithelium in all groups of patients. However, in the untreated coeliac patients fluorescence was also demonstrated in the basement membrane and connective tissue of the mucosa (returning to normal on treatment).On the basis of our findings, a revised pathway for the normal production of 11S IgA is proposed as well as an additional pathway involving a ;backflow' of 11S IgA into the lamina propria in pathological states such as coeliac disease. This backflow is reversed by an adequate gluten-free diet. It is suggested that 7S IgA and 11S IgA may be involved in immune reactions in the mucosa with antigens such as gluten.     

Levels of salivary IgA in treated and untreated coeliac disease

Estimations of the concentration of secretory IgA have been performed on 152 specimens of saliva from 46 patients with adult coeliac disease. The results are compared with values observed in 20 normal subjects. The mean salivary IgA concentration was 9 mg% in 36 patients on a normal diet and 7.9 mg% in 21 patients on a gluten-free diet. In 20 normals the mean salivary IgA was 7.1 mg%. Nine patients were studied before and after gluten exclusion. Seven of these showed a marked fall in salivary IgA concentration after gluten was excluded.     

IgA anti-tissue transglutaminase: setting the stage for coeliac disease screening.

Coeliac disease is triggered in genetically predisposed individuals by the ingestion of wheat and related cereals. Affected persons raise an intestinal mucosal T-cell response against the gluten fraction of these cereals. Furthermore, they produce characteristic circulating IgA antibodies to a self-antigen present in the extracellular matrix that can be detected on tissue sections. The positive predictive value of these endomysial, reticular or umbilical cord antibodies for coeliac disease comes close to 100%. Recently, the enzyme tissue transglutaminase was identified as the main, if not sole, endomysial autoantigen in coeliac disease. Enzyme-linked immunosorbent assay tests with tissue transglutaminase from guinea pig or the recombinant human enzyme have been established that allow a standardized and quantitative determination of IgA anti-tissue transglutaminase titres. While the published assay variants report high positive and negative predictive values for coeliac disease, they were applied to preselected patients from mostly single centres. Therefore, validation and in part cross-validation of a standardized assay based on guinea pig tissue transglutaminase in 38 European and non-European centres is timely. With a sensitivity of 90% and specificity of 96% relative to local diagnostic standards the assay performed well. Considering further improvement by the use of recombinant human tissue transglutaminase as the antigen and central re-evaluation of the local standards for confirmation of coeliac disease, this enzyme-linked immunosorbent assay promises to become the primary tool for non-invasive diagnosis, therapy control and screening of coeliac disease. However, with an estimated prevalence of 1:100-1:200 of mostly atypical and subclinical coeliacs in Western populations, we are confronted with the question of how far mass screening is ethically feasible and cost effective.     

Isolated IgA deficiency accompanied by autoimmune thyroid disease.

Selective immunoglobulin (Ig) A deficiency is reported to occur in 1 in 16,000 in Japan and has been reported to be complicated with various autoimmune diseases. A 49-year-old woman was diagnosed as having autoimmune thyroid disease. Her serum IgA, IgM and IgG were revealed to be 4.1, 154 and 1930 mg/dl, respectively. Severe skin eruption which occurred with 30 mg/day of methimazole (MMI) or 300 mg/day of propylthiouracil (PTU), was relieved by reducing MMI to 15 mg/day and administering anti-allergic drugs. Although the influence of IgA deficiency on autoimmunity and allergy still remains unclear, this is a report of IgA deficiency associated with autoimmune thyroid disease.     

Selective IgA deficiency and Pi ZZ-antitrypsin deficiency. Association with recurrent sinopulmonary infections, emphysema, and bronchiectasis.

We describe a patient in whom selective IgA deficiency and homozygous alpha1-antitrypsin deficiency were discovered. Clinically, the patient suffered from chronic sinopulmonary infections, destructive emphysema, and bronchiectasis. The interrelation of IgA and alpha1-antitrypsin was studied. Twenty-three alpha1-antitrypsin-deficient sera were screened for IgA deficiency. None of these sera were deficient in IgA. Fifteen IgA-deficient sera were screened for alpha1-antitrypsin deficiency. In this group, three patients were found to have variant alpha1-antitrypsin phenotypes. Respiratory infections were a prominent complaint in all three of these patients, with bronchiectasis in two patients. We believe that the combination of IgA and alpha1-antitrypsin deficiencies should be considered in the evaluation of any patient with idiopathic bronchiectasis.     

Granulomatous disease in selective IgA deficiency

Although common variable immunodeficiency (CVID) is sometimes associated with sarcoidosis/granulomatous disease, there have only been isolated reports of selective immunoglobulin A (IgA) deficiency and granulomatous disease. We present a patient with IgA deficiency who developed Heerfordt syndrome, a variant of neurosarcoidosis. This specific entity has not been previously reported to occur in IgA deficiency. Our case expands the reported associations of IgA deficiency and provides another example to the paucity of reported cases of sarcoidosis occurring in patients with IgA deficiency. As CVID and IgA deficiency have common underlying genetic factors, such an association is biologically plausible.     

Do IgA antigliadin and IgA antiendomysium antibodies show there is latent coeliac disease in primary IgA nephropathy?

The finding in primary IgA nephropathy of increased levels of IgA to food antigens and particularly to gliadin prompted the hypothesis that a subgroup of these patients may have latent coeliac disease. The observation that gliadin may experimentally induce IgA mesangial deposits supported this hypothesis. We evaluated specific immunological markers of coeliac disease (antiendomysium antibodies) which parallel histological changes of gluten sensitive enteropathy, and an IgA immunofluorescent test for antigliadin antibodies in 18 patients with IgA nephropathy, in 56 untreated coeliac disease patients, in 254 controls (58 healthy and 196 disease controls). Antiendomysium antibodies were positive in 89.28% of coeliac patients, but negative in all IgA nephropathies and controls. IgA immunofluorescent test for antigliadin antibodies, negative in all IgA nephropathy patients, was positive in 76.78% of coeliac patients and in 4.91% of controls. ELISA IgA antigliadin antibodies were negative in controls, but positive in 22.22% of IgA nephropathy patients and in 60.71% of coeliac patients. Our data would suggest that in most patients with IgA nephropathy there is no evidence of latent coeliac disease.