Antireticulin Antibodies Research Articles

High frequency of celiac disease in Down syndrome

We screened 115 children with Down syndrome for celiac disease, using antigliadin, antiendomysium, and antireticulin serum antibodies and an intestinal permeability test. Celiac disease was diagnosed in eight children, giving a frequency of 7.0%. We recommend screening for celiac disease in all persons with Down syndrome, with the use of at least the antiendomysium antibody determination. (J P EDIATR 1996;128:555-7)

Autoantibodies following Parvovirus B19 infection

This study was undertaken to assess the incidence and significance of autoantibody production following B19 infection, 53 patients with acute B19 infection (positive for serum anti-B19 IgM) were studied; symptoms were rash and arthralgia (n = 26), rash (n = 7), arthralgia (n = 16), aplastic crisis (n = 3), and intrauterine death (n = 1). These patients were followed for 26-85 months (mean 57 months) and re-assessed for persistent symptoms, serum anti-B19 antibodies, and serum autoantibodies. At follow-up, 14 test and two control patients had one or more serum autoantibodies (anti-nuclear antibody, anti-smooth muscle antibody, gastric parietal cell antibody, anti-reticulin antibody, anti-mitochondrial antibody, rheumatoid factor) at a titre of > or = 40 (P = 0.004). Seven test patients and no control patients had serum autoantibody at a titre > or = 160. Of these seven test patients, only one had persistent symptoms. At follow-up assessment, this woman was 48-year-old, had persistent arthralgia for 4 years following acute B19 infection, rheumatoid factor at a titre of 160 (1920 IU/ml), and had been independently diagnosed as having rheumatoid arthritis. In conclusion, results of the present study showed that low titre autoantibody production was common following symptomatic B19 infection, however, while interesting from a virological standpoint, this finding may be of little significance for future development of autoimmune disease.

Value of serologic markers for clinical diagnosis and population studies of coeliac disease.

There is a need for serologic markers in selecting patients with symptoms compatible with coeliac disease for intestinal biopsy and for population screening. Few comparative studies have been done. Sera from 55 patients with coeliac disease and 65 referents, aged between 8 months and 79 years, were investigated. Anti-gliadin, anti-reticulin, anti-endomysium, and anti-jejunal antibodies were measured. The sensitivities, specificities, and positive predictive values for different disease prevalence levels were calculated. Confidence intervals, rarely used in this type of study, were calculated. In most tests the antibody levels were age-correlated. The highest sensitivities in combination with high specificities were found for IgA anti-gliadin antibodies in children less than 5 years of age and IgA anti-endomysium antibodies in older children and adults. These tests were most useful for testing a population with a high disease prevalence, such as patients with gastrointestinal symptoms, although the results for many tests had overlapping confidence intervals. For screening unselected populations with a low disease prevalence, in which a test with maximum specificity is desired, only anti-endomysium antibodies had sufficiently high predictive value to be of practical use.

Adult Celiac Disease: Report of a Case

Adult Celiac Disease: Report of a Case

Screening for asymptomatic celiac sprue in families.

We evaluated the reliability of IgA and IgG antigliadin antibodies (AGA-A, AGA-G), antireticulin antibody (ARA), endomysial antibodies (EmA), and alpha 1-antitrypsin clearance (alpha 1-AT CL) in the detection of celiac sprue (CS) in 59 first-degree asymptomatic relatives of celiac patients who had duodenal biopsy. Twenty-four relatives who had normal results of screening tests were selected at random for biopsy; 35 relatives with at least one abnormal test result were biopsied. Eleven relatives were noted to have villous atrophy at biopsy; the diagnosis of celiac sprue was confirmed by histological improvement after gluten-free diet in six. AGA-G, alpha 1-AT CL, and EmA had sensitivities of 73%, 73%, and 64%, respectively, with very high levels of specificity. Sensitivity was improved by the combination of two serological markers (AGA-G + alpha 1-AT CL = 91%; AGA-G + EmA = 82%; EmA + ARA = 82%). Furthermore, combination of EmA and ARA has shown the best specificity and positive predictive value. AGA-G, alpha 1-AT CL, and EmA are reliable individual markers for the detection of asymptomatic celiac sprue. However, a combination of two of them, including ARA, was more sensitive than the individual tests.

6 Coeliac disease in childhood

Coeliac disease usually presents in infancy or early childhood with diarrhoea, vomiting and interference with weight gain and growth. Withdrawal of dietary gluten is followed by resolution of the symptoms and signs and restoration of normal weight gain and growth; the characteristic subtotal villous atrophy of the jejunal mucosa also recovers. Later re-introduction of dietary gluten will lead to a return of the jejunal mucosal abnormality in the majority and to clinical relapse in many but not all. The severity and timing of both are variable and 5% of children initially considered on clinical, biopsy and gluten response evidence to have coeliac disease appear to develop permanent tolerance to gluten, although mucosal relapse may occur years after the re-introduction of dietary gluten in a minority, emphasizing the need for long-term follow-up. Although a diagnostic and subsequent follow-up jejunal biopsy are necessary to confirm the diagnosis, anti-gliadin IgA and IgG, anti-reticulin and anti-endomysium antibodies are now almost totally reliable in identifying children who have coeliac disease and are valuable in monitoring the adequacy of gluten withdrawal. Dietary compliance is frequently poor and regular supervision by a paediatric dietitian is needed; indeed, lifelong supervision to ensure gluten withdrawal is essential to reduce the chance of developing later gastrointestinal malignancy.

Antineutrophil cytoplasmic antibodies (ANCA) in idiopathic pulmonary hemosiderosis

Four children were diagnosed with idiopathic pulmonary hemosiderosis (IPH), over a period of 4 years. Retrospectively, antineurtrophil cytoplasmic antibodies (ANCA) were studied by indirect immunofluorescence (IIF) and ELISA in 18 sera from these patients, stored at -20 degrees C. ANCA-positive sera, from 1/20 to 1/1, 200 dilution, were found in 3/4 of the patients, by IIF. The patient with the highest titre of ANCA died 3 months later during an acute crisis, the other two patients need a minimal dose of steroids. In one case only, a patient who is still without treatment, had no ANCA. The antibodies anti-myeloperoxidase and anti-proteinase-3 were negative or at border line levels. Rheumatoid factor, antinuclear (Hep-2), anti-endomysial, anti-reticulin and antibasement membrane antibodies were negative in all sera. The surviving patients were followed-up for more than 10 years with no systemic or renal disease appearances. The presence of serum ANCA may help to classify children with pulmonary haemorrhage and may have a prognostic value.

Autoimmune phenomena in children with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

We have studied sera from 44 children with Human Immunodeficiency Virus infection and Acquired Immunodeficiency Syndrome using immunoblotting, radioimmunoassay, enzymoimmunoassay and indirect immunofluorescence. We have detected a low incidence of antinuclear (2.9%), anti-reticulin (2.9%) and anti-smooth muscle (14.7%) antibodies by indirect immunofluorescence. By enzymoimmunoassay we have detected anti-dsDNA (20.5%) and anti-ENA [anti-nRNP (61.3%), anti-Sm (29.5%), anti-Ro (47.7%) and anti-La (18.1%)] antibodies. Tests for anti-dsDNA by radioimmunoassay were negative, suggesting the presence of low-avidity anti-DNA antibodies. By immunoblotting we have detected anti-C (nRNP) (33.3%), anti-BB' (Sm) (33.3%), anti-Ro (60 KD) (4.5%) and anti-La (11.3%) antibodies. The presence of anti-Ro antibodies was associated with progressive neurological disease. Long-term follow-up studies with larger numbers of patients are necessary to evaluate the clinical significance of the presence of anti-dsDNA and anti-ENA antibodies in children infected with Human Immunodeficiency Virus.

307 ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) IN CHILDREN PREVIOUSLY DIAGNOSED OF IDIOPATHIC PULMONARY HEMOSIDEROSIS (IPH)

Four children were diagnosed of IPH, during a period of 4 years. Retrospectively, ANCA were studied by indirect immunofluorescence (IIF) and ELISA in 18 sera of these patients, stored at -20°C. ANCA positive sera, from 1/20 to 1/1,200 dilution, were found in sera of 3/4 of the patients, by IIF. The patient with the highest titre of ANCA died 3 months later during an acute crisis. The only case, in permanent remission without treatment, has no ANCA. The other two patients need a minimal dose of steroids. The antibodies anti-myeloperoxidase and anti-proteinase-3 were negative or in questionable levels. Rheumatoid factor, anti-nuclear (Hep-2), anti-endomysial, anti-reticulin and anti-basement membrane antibodies were negative in all sera. The surviving patients were followed-up for more than 10 years with no systemic or renal disease appearences. Serum ANCA must be studied in patients diagnosed of IPH. The presence of these antibodies may have a prognostic value although their lessive role is still discussed.

IgA antibodies against reticulin and endomysium in the serum and gastrointestinal secretions of patients with dermatitis herpetiformis.

Although IgA is present in the skin of patients with dermatitis herpetiformis (DH), the relationship of that IgA to the mucosal immune response is not known. The purpose of this study was to determine if IgA antibodies directed against tissue antigens, which are present in the serum of patients with DH, are also present in the gut secretions of these patients. Serum and gut secretions from 8 patients with DH and 5 control subjects were analyzed by indirect immunofluorescence for the presence of IgA antireticulin and antiendomysium antibodies. IgA antibodies against reticulin (3 of 8 patients) and endomysium (4 of 8 patients) were found in the serum of patients with DH. IgA antibodies were also present in the gut secretions of all of these patients, but not in subjects (patients with DH and controls) that did not have serum IgA antireticulin or antiendomysium antibodies. The presence of IgA antireticulin and antiendomysium in both the serum and gut secretions of DH patients suggests that these antibodies arise as a result of the mucosal immune response and that IgA of mucosal origin can persist in the serum of patients with DH.

Antigliadin and Antireticulin Antibodies in Celiac Disease and Other Forms of Protracted Diarrhea in Kuwait

Sera were collected from 18 children with celiac disease and 49 children with other forms of chronic diarrhea. Of the 49 children with other forms of chronic diarrhea, 35 had postenteritis, 8 had giardiasis and 6 had other diagnoses. Thirty children with nongastrointestinal disorders were tested and used as controls. The sera were tested for gliadin, α-gliadin and reticulin antibodies: false-positive values in children with other forms of chronic diarrhea were encountered in 27, 45, and 4% and in 3, 3, and 0% of controls, respectively. The sensitivity in celiac disease was 89,89 and 50%, while the specificity was 71 49 and 94%, respectively. In Kuwait, postenteritis syndromes are common causes of protracted diarrhea. Antibodies to gliadins are as sensitive but significantly less specific for celiac disease (CD) than those reported in developed countries. The combined testing of antigliadin and antireticulin antibodies raised the diagnostic specificity to 94%.

Serological screening suggests that adult coeliac disease is underdiagnosed in the UK and increases the incidence by up to 12%.

Because coeliac disease often presents atypically it is underdiagnosed. It is suggested that the detection rate may be increased by 12% if serology is used to identify cases of occult enteropathy. All adults noted incidentally to be R1 anti-reticulin antibody (ARA) positive in the course of routine autoantibody testing of 6532 sera over one year were followed. None of the eight patients with seropositive serum was suspected of having coeliac disease. All eight had high titres of IgA anti-gliadin and IgA anti-endomysial antibodies, neither of which is detected in a routine autoantibody test, in addition to IgA R1-ARA. On clinical review coeliac disease was considered probable in only one patient, but because of the strong serological evidence of gluten sensitivity, jejunal biopsy was advised in all eight. Seven agreed and all had villous atrophy and crypt hyperplasia in keeping with coeliac disease. Six of the seven presented initially with vague symptoms such as tiredness or arthralgia. These symptoms disappeared after several weeks of gluten withdrawal. Forty two sera showing reticulin staining patterns other than R1 were used as controls. Low titre IgA anti-gliadin was noted in two of 42 but none had IgA anti-endomysial antibody. These 42 cases were not recommended for biopsy. During our study 58 other new adult cases of coeliac disease were diagnosed, primarily on clinical rather than serological grounds, at the four hospitals that request autoantibody studies. Occult coeliac disease detected serologically thus increased the overall incidence of coeliac disease by 12% from 58 to 65 cases. R1-ARA, even in the absence of the expected symptoms and signs of coeliac disease, is an indication for jejunal biopsy and is a reliable indicator of occult coeliac disease.

Serum IgA anti-gliadin antibodies in an adult population sample

IgA-class anti-gliadin antibodies (AGA) and IgA-, IgG-, IgM-class anti-reticulin antibodies (ARA) were determined in 1461 persons, representing 84% of a population from the village of Karksi-Nuia. AGA were detected by enzyme-linked immunosorbent assay (ELISA) and ARA by indirect immunofluorescence. Fifty-two (3.5%) persons had IgA-class AGA, of whom 48 and an additional three of four persons with diarrhea were biopsied. All biopsies showed normal small intestinal mucosal architecture. All 1461 persons were negative for ARA. Our results demonstrate that AGA are frequently detected in an adult Estonian population and positivity increases with age in persons with normal small intestinal mucosa. Positivity for AGA does not predict silent undetected celiac disease but rather represents a normal response to dietary antigens in the elderly. Inability to detect ARA suggests that celiac disease does not exist in this population. As none of the AGA-positive but ARA-negative biopsied persons had celiac disease, ARA might be a more specific serologic marker for celiac disease than AGA.

Purification of Fibroblast-Derived Celiac Disease Autoantigen Molecules

We have recently purified autoantigen polypeptides reacting with celiac disease patient sera IgA from the extracellular noncollagenous matrix compartment of fetal lung tissue. These molecules trigger the production of different tissue antibodies, the so-called antireticulin and antiendomysium antibodies in celiac disease. In the present report, we show that fibroblasts synthesize and secrete celiac disease autoantigen molecules. The secretion product, reactive with IgA from celiac disease patients, is a large-molecular-weight protein aggregate. When the protein complex was treated with 4 M guanidinium hydrochloride and 0.1% SDS, 11 monocomponent polypeptides could be detected by PAGE. Of these, four single polypeptides with molecular weights of 17,000-39,500 and isoelectric points of 5.0-7.0 were observed to react with IgA separated from sera of children with celiac disease. The polypeptide molecules produced by fibroblasts in vitro bound to antireticulin and antiendomysium antibodies but not to antigliadin antibodies. The present observations show that tissue antibodies found to be specifically associated with celiac disease are generated against a synthesis product of fibroblasts, a cell-type known to synthesize a number of biologically active polypeptides. The fibroblast-derived extracellular matrix proteins and the formed autoantibodies may be important in the pathogenesis of gluten-sensitive enteropathy.

Anti-reticulin antibody (ARA) in gluten-sensitive enteropathy

Anti-reticulin antibody (ARA) in gluten-sensitive enteropathy

Anti-reticulin antibody in gluten sensitive enteropathy

Journal Article Anti-reticulin antibody in gluten sensitive enteropathy Get access D.J. Unsworth, D.J. Unsworth Department of Clinical Immunology Addenbrooke's HospitalHills Road Cambridge Search for other works by this author on: Oxford Academic PubMed Google Scholar D.L. Brown D.L. Brown Department of Clinical Immunology Addenbrooke's HospitalHills Road Cambridge Search for other works by this author on: Oxford Academic PubMed Google Scholar QJM: An International Journal of Medicine, Volume 86, Issue 2, February 1993, Pages 135–136, https://doi.org/10.1093/oxfordjournals.qjmed.a068774 Published: 01 February 1993

Detection of Undiagnosed Coeliac Disease with Atypical Features Using Antireticulin and Antigliadin Antibodies

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.

Antireticulin antibodies in sera of children with insulin-dependent diabetes mellitus

Sera from 125 children (mean age 9.5 ± 3.9; range 0.5–18 years) with newly diagnosed insulin-dependent diabetes mellitus were examined for the presence of antireticulin antibodies (ARA). Fifty-four of these children were followed up over a period of 150–400 days after the onset of the disease with respect to their serum ARA. The indirect immunofluorescence method on human and rat tissue was used to detect autoantibodies. In each serum, the level of islet cell antibodies (ICA) was determined. The prevalence of ARA in our diabetic children (16%) was significantly higher than in normal population ( P < 0.05). In sera of newly diagnosed ICA-negative children, ARA were more frequent than in ICA-positive patients ( P < 0.025). The difference in ARA prevalence was even higher when patients were divided into two groups one with less and one with more than 30 JDFu ( P < 0.005). On the contrary, sera sampled 150–400 days after the manifestation of IDDM revealed neither a positive nor a negative association between ICA and ARA. Thus, the negative association of ARA with ICA in the early stages of IDDM may suggest the role of an autoimmune response to reticulin in part of the IDDM patients, and gives further evidence to the heterogeneity of IDDM.

Prevalence of anticardiolipin antibodies in the elderly British population

In a cross-sectional study of 100 healthy elderly individuals, anticardiolipin antibodies (aCL) were measured using an ELISA technique. aCL were not detected in the majority of subjects (63%), and in the remaining 37% titres were within the laboratory reference range (mean +5 standard deviations) previously determined for adults of all ages. In contrast, significant titres of IgM rheumatoid factor were found in 10%, antimitochondrial antibody in 13%, antinuclear factor in 5%, anti-smooth muscle antibody in 18%, antiparietal cell antibody in 10%, and antireticulin antibody in 1%. Antibodies to single or double-stranded DNA were not detected in any subject. We conclude that, although other auto-antibodies may be present in the healthy aging population in Britain, abnormally elevated levels of aCL antibody do not occur, and when present may be an indicator of autoimmune-mediated pathology.

Extracellular Binding Sites on IGA Anti-Jejunal Antibodies on Normal Small Bowel Detected by Indirect Immunoelectronmicroscopy

Patients with dermatitis herpetiformis (DH) have IgA deposition in the papillary dermis and in the lamina propria of the small bowel. In addition, most of DH patients' sera contain IgA class anti-reticulin antibodies, anti-endomysium antibodies (EMA), and anti-jejunal antibodies (JAB) during times of gluten intake. In previous studies, JAB and EMA seemed to be identical and related to the group of anti-reticulin antibodies. In the present study, pre-embedding en bloc immunoelectronmicroscopic methods were applied for analysis of the ultrastructural binding sites of JAB on monkey and rabbit small bowels. These substrates were incubated with sera from DH patients strongly positive for JAB. Simultaneous investigations with the PAP technique and with 5 nm gold-labeled protein A or second antibodies visualized the bound IgA identically: it was associated with collagen fibrils underlying the epithelial and cryptal basement membranes and with collagen fibrils around capillaries. Staining was also detected along the endomysial collagen fibrils of smooth muscle layers, around elastica and smooth muscle cells of blood vessel walls, and along collagen fibrils near smooth muscle cells in the lamina propria. Neither the peroxidase product nor gold deposition was detected directly on the fibers, but was associated with amorphous material surrounding collagen fibers of different diameters. The distribution of JAB-stained structures corresponded to the localization of reticulin network of the small bowel. Our data indicate that JAB recognize an antigen or antigens associated with an amorphous component of the reticulin-collagen structure of jejunum and may have identical binding sites, as anti-reticulin antibodies and EMA.