B. Pedini

Clinical and subclinical organ-specific autoimmune manifestations in Type 1 (insulin-dependent) diabetic patients and their first-degree relatives

SummaryStudying 239 Type 1 (insulin-dependent) diabetic patients and 144 of their first-degree relatives, we found a significant prevalence of autoimmune manifestations in both groups, compared with sex-and age-matched control subjects (p< 0.001). In particular, in diabetic patients we found a high frequency of autoimmune thyroid disease and idiopathic Addisons disease and also a significant prevalence of thyroid (p< 0.001), parietal cell (p< 0.05) and adrenal antibodies (p< 0.05). In the relatives a high frequency of thyroid disease, thyroid, parietal cell and adrenal antibodies and a significant prevalence of islet cell antibodies (p< 0.05) were detected. In both groups functional glandular tests and gastric biopsies performed on the basis of autoantibody positivity revealed 13 examples of subclinical hypothyroidism, two cases of reduced adrenocortical reserve and five of atrophic gastritis. Autoantibody screening in diabetic patients and their relatives permitted the early diagnosis of the underlying endocrine disorders.

COMPLEMENT-FIXING ADRENAL AUTOANTIBODIES AS A MARKER FOR PREDICTING ONSET OF IDIOPATHIC ADDISON'S DISEASE

In a prospective investigation of the role of adrenal autoantibodies (AA) in predicting the onset of idiopathic Addisons disease, 9 initially non-addisonian AA-positive autoimmune subjects were followed for 42 months. In 4 of these subjects Addisons disease developed within 1-31 months. A fifth had reduced adrenocortical reserve at the start and at the end of the investigation. An AA capable of fixing the membrane attack complex of complement [(C5-C9) F-AA] was detected before onset of the disease in the sera of the 4 patients in whom Addisons disease developed. (C5-C9) F-AA may be involved in the pathogenesis of idiopathic Addisons disease and may be regarded as a marker for individuals in whom idiopathic adrenal insufficiency is likely to develop.

Islet cell and insulin autoantibodies in organ-specific autoimmune patients. Their behaviour and predictive value for the development of Type 1 (insulin-dependent) diabetes mellitus. A 10-year follow-up study

SummaryTo evaluate the behaviour and predictive value of islet cell and insulin autoantibodies in patients with organspecific autoimmune diseases, we followed 21 non-diabetic subjects for a mean period of 84±27 months. Ten patients were persistently seropositive for complement-fixing islet cell antibodies and high titres of immunoglobulin G islet cell antibodies (≥ 1∶8). The prevalence of persistent insulin autoantibodies in this group was 67%. Seven patients (70%) developed Type 1 (insulin-dependent) diabetes mellitus after a latency period of 2–60 months. The predictive value of complement-fixing islet cell antibodies was 65%, and in the presence of both complement-fixing islet cell and insulin autoantibodies the predictive value rose to 76%. Eleven patients were seronegative for complement-fixing islet cell antibodies and had low immunoglobulin G islet cell antibodies titres (< 1∶8) that were either persistent or transient, or that fluctuated during follow-up. The prevalence of persistent insulin autoantibodies in this group was 45%; only one subject developed Type 1 diabetes. The predictive value of persistent islet cell antibodies (complement-fixing positive/negative) was 54%, and it rose to 70% when both islet cell and insulin autoantibodies were present. Individuals with only insulin autoantibodies or immunoglobulin G islet cell antibodies did not develop diabetes mellitus. A high frequency of HLA-DR3 and/or DR4 was found in patients who developed diabetes mellitus. Thus, the presence of both islet cell and insulin autoantibodies in patients with organ-specific autoimmune disease appears to confer the highest risk of progression toward Type 1 diabetes.

Helicobacter pylori Infection and Gastric Autoimmune Diseases: Is There a Link?

Background.  Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity.

Clinical, subclinical and potential autoimmune diseases in an Italian population of children with coeliac disease

Background  Several studies have suggested a link between coeliac disease and other autoimmune diseases.

The natural history of pre-Type 1 (insulin-dependent) diabetes mellitus in patients with autoimmune endocrine diseases

SummaryAn 11-year prospective study was carried out in 180 non-diabetic patients with organ-specific autoimmune diseases to evaluate islet cell antibodies in predicting Type 1 (insulin-dependent) diabetes mellitus. Islet cell antibodies were characterised according to titres, persistence, complement-fixing ability, and pattern. During follow-up, 14 of 46 patients with islet cell antibodies persistently greater than 5 Juvenile Diabetes Foundation Units (JDF-U) (30.4%), none of 23 with islet cell antibodies between 2.5 and 5JDF-U or fluctuating, and 3 of 109 without islet cell antibodies (2.7%), developed diabetes. The cumulative risk of developing diabetes was 70%, 0%, and 4%, respectively. All the patients who developed diabetes were females. Eight progressed to insulin-dependence acutely, four showed a transient period of non-insulin-dependence, while two were still insulin-free. No difference was found in titres of islet cell antibodies for the risk of diabetes. Complement-fixing islet cell antibodies enhanced the cumulative risk for the disease in patients with conventional islet cell antibodies at low-middle (≥2.5–40 JDF-U), but not at high (≥80 JDF-U) titres. Forty-two patients with islet cell antibodies were investigated for the whole or the selective pattern. In the presence of the whole pattern the cumulative risk for diabetes rose to 100%, while with the selective pattern it declined to 34%. The whole pattern was found in 83% of patients who developed Type 1 diabetes acutely. In patients with organ-specific autoimmune diseases, the whole islet cell antibody pattern greatly enhances the prediction for diabetes.

Assessment of adrenocortical function and autoantibodies in a baby born to a mother with autoimmune polyglandular syndrome Type 2

We describe the case of a baby born to a mother with Addison’s disease in the context of Autoimmune Polyendocrine Syndrome Type 2._Adrenal cortex autoantibodies and steroid 21-hydroxylase autoantibodies were detectable in the sera of both mother and baby, suggesting the transplacental passage of these autoantibodies. Adrenal autoantibodies were present in the baby’s serum at delivery, at 3, 6 and till 34 months of age but no signs of clinical or subclinical adrenal insufficiency were found in the baby during the observation period. These data suggest that the presence of adrenal autoantibodies in serum alone is not a sufficient cause for the development of autoimmune adrenalitis.

Low Frequency of Autoantibodies to Islet Cell, Glutamic Acid Decarboxylase, and Second‐Islet Antigen in Patients with Gestational Diabetes Mellitus

Abstract: The aim of the study was to determine the frequency of patients with gestational diabetes mellitus (GDM) who have serological markers typical of autoimmune type 1 DM. The specific pancreatic markers, ICAs, glutamic decarboxylase (GADAbs), and second islet antigen (IA2Abs), were measured in 70 women with GDM during the pregnancy and after delivery. ICAs were measured by indirect immunofluorescence and GADAbs and IA2Abs were determined by a radiobinding assay with recombinant antigens. On entering the study, 1 of 70 (1.4%) patients was positive for both ICAs (80 JDF‐U) and GADAbs (167 U/mL), while another (1.4%) was positive for ICAs (40 JDF‐U). None of the patients was positive for IA2Abs. During follow‐up, positivity was maintained unchanged in the two positive patients. Four previously negative patients had seroconversion: one for both ICAs (20 JDF‐U) and GADAbs (49.3 U/mL) and the other three for GADAbs (1.8, 1.4, and 15.3 U/mL, respectively). The IA2Abs remained negative in all patients. Overall, during the observation period 6 of 70 (8.6%) patients had or developed autoantibodies against endocrine pancreas. During follow‐up 15 patients developed clinical DM (10 type 2, 5 type 1) and 7 demonstrated impaired glucose tolerance (IGT) after OGTT. No correlations were demonstrated between the immunological patterns and the evolution in DM. In patients with GDM, the frequency of pancreatic autoantibodies varies during the pregnancy and after delivery, but a small subgroup of patients bearing these markers is identifiable. GDM is a complex syndrome, constituted by different types of diabetes mellitus where the autoimmune form is very rare.

Complement-fixing gastric parietal cell autoantibodies. A good marker for the identification of type A chronic atrophic gastritis.

Using an indirect immunofluorescence (IIF) technique, gastric parietal cell autoantibodies of IgG class (GPCA-IgG) were found in 2% of a normal population, in 5-26% of organ-specific autoimmune subjects and in 100% of patients with pernicious anaemia. With the exception of subjects with alopecia, there was a significantly increased prevalence of GPCA-IgG in autoimmune patients with respect to normal controls. GPCA of IgA class were detected in 22% of GPCA-IgG positive subjects, whereas GPCA of IgM class were uncommon. One-hundred and fifteen subjects underwent gastroscopy and body mucosal biopsy. Histopathological findings of chronic atrophic gastritis (CAG) were present in 71% of GPCA-IgG positive autoimmune patients without pernicious anaemia, in 100% of GPCA-IgG positive patients with pernicious anaemia, and in 20% of GPCA negative autoimmune patients. Complement-fixation test was performed in 46 GPCA-IgG positive subjects without pernicious anaemia using the IIF method. Twenty-nine patients (63%) were found to fix complement fractions till C9 (CF-GPCA) together with properdin factor, and in 25 of them (86%) the histological examination of body gastric mucosa disclosed a CAG (P = 0.0003 versus GPCA-IgG positive/CF negative controls). No significant difference was observed for the prevalence of CAG in GPCA-IgG positive/CF negative subjects with respect to GPCA-IgG negative control group. We conclude that the presence of CF-GPCA represents a useful immunological marker in the identification of CAG, while no predictive value seems to be associated with non-complement fixing GPCA-IgG.

Expression of class I and II human leukocyte antigens by thyrocytes and lymphocytic infiltration on human thyroid tumors. An immunofluorescence study

Surgical thyroid sections from 30 papillary carcinomas (PC), six medullary carcinomas (MC), three anaplastic carcinomas (AC), two follicular carcinomas (FC), and 16 adenomas (AD) were examined with an indirect immunofluorescence technique employing different monoclonal antibodies to evaluate the expression of human leukocyte antigen (HLA)‐A, B, C (Class I) and DR, DP, DQ (Class II) by thyrocytes, together with the phenotype and distribution of inflammatory cells. Ten PC and four FC were also investigated for the presence of intercellular adhesion molecule‐1 (ICAM‐1). In situ deposits of immunocomplexes and circulating thyroid autoantibodies were also evaluated. An increased expression of Class I antigens was found in all PC and FC, in 33% of MC and AC, and in 31% of AD. An anomalous expression of Class II antigens was observed in 70% of PC, in 50% of FC, in 33% of AC, in 19% of AD, and in none of the MC. Expression of DP or DQ was revealed only in a portion of the DR‐positive glands. A reduction of microsomal autoantigen expression was found. No ICAM‐1‐positive thyrocytes were detected. A moderate T‐lymphocytic infiltrate was noticed only in PC, where it was correlated with DR and DP and/or DQ coexpression. B‐cells and natural killer cells were virtually absent. The authors speculate that the weak Class II antigens expression, together with the partial or complete loss in microsomal autoantigen and the absence of ICAM‐1 by thyrocytes, may account for the limited engagement of immunocompetent cells observed in thyroid tumors.