A. Caretto

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.

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.

Localization of met-enkephalin on human spermatozoa and evidence for its physiological role.

Pro-opio-melano-cortino-derived peptides have been identified in rat testicular extracts and in human seminal plasma, but their physiological role is still unknown. We report that met-enkephalin is localized on human spermatozoa, by means of an indirect immunofluorescent technique. Furthermore, we demonstrate that a met-enkephalin analog (D-Ala2-Mephe4-Met-(o)-ol-enkephalin, FK 33-824, Sandoz, Basel, Switzerland: DAMME) inhibits in a dose-dependent manner the acrosome reaction induction. The hypothesis of a physiological role of seminal met-enkephalin on human spermatozoa fertilizing ability is briefly discussed.

Study of Class I and Class II Antigen Expression and Lymphocytic Infiltrate on Thyroid Tumors

Class II (HLA-DR) antigens, encoded by genes located in the HLA region, play a key role in antigen presentation and in imrnunoresponse regulation. The expression of these membrane-associated molecules is normally restricted to B and T-activated lymphocytes, antigen-presenting cells (macrophages, Kupffer, dendritic and Langherans cells, etc.) and capillary endothelium (1). On the contrary, class I (HLA-ABC) antigens are normally present, with different expression, on the membranes of all nucleated tissue cells and platelets (2). The recent observation that in thyroid autoimmune diseases there exists an aberrant epithelial expression of class II and an increased expression of class I molecules by target cells, and the finding that this phenomenon is associated with an infiltration of T lymphocytes (3) permitted new interpretations about the pathogenetic events leading to thyroid autoimmunity and, extensively, to organ-specific autoimmunity (4). Recently it has also been found that paraffin-embedded tissues of different thyroid tumors have an aberrant exhibition of class II molecules and that the lymphocytic infiltration is correlated to HLA expression (5). The aim of this work was to study on unfixed cryostat sections of different thyroid tumors the epithelial expression of class I and class II molecules, the characteristics of the infiltrating cells and the connection between these two events.

Islet cell surface antibodies by an ELISA method in diabetic and nondiabetic patients

Islet cell surface antibodies (ICSA) were investigated by an ELISA method using a commercial kit in 146 subjects with and without islet cell antibodies (ICA): 28 with insulin-dependent diabetes mellitus (IDDM), 24 with noninsulin-dependent diabetes mellitus (NIDDM), 22 first-degree relatives (FDR) of IDDM patients, 31 organ-specific autoimmune patients (OSAP), 21 nonautoimmune hospitalized patients (NAP), and 20 ICA-negative normal controls. Furthermore, insulin autoantibodies (IAA) were evaluated in 87 of these subjects. ICSA were found in 11% of IDDM patients and in 14% of their FDR, in 4% of NIDDM patients, in 10% of OSAP, in 10% of NAP, and in 5% of normal controls. After absorption with rat liver powder, ICSA were detected in 7% of IDDM patients, in 5% of their FDR, in 4% of NIDDM, in 6% of OSAP, in 5% of NAP and in none of normal controls. ICSA were also detected in 4% of IAA-positive compared to 3% of IAA-negative sera. Neither correlation was found between ICSA and ICA in each group of subjects, nor between ICSA and IAA, suggesting that these autoantibodies recognize different pancreatic targets. Moreover, no significant difference was observed for ICSA prevalence in the various groups of patients studied when compared with normal controls. The prevalence of ICSA assessed by this ELISA method has been compared to that reported by other workers, who employed different techniques. We also discuss here the pathogenetic role and the clinical relevance of the most common markers of pancreatic autoimmunity. We conclude that the role of ICSA as possible indicators of β cell damage still remains to be evaluated in humans, and that the standardization of such antibodies is an essential prerequisite for understanding their actual prevalence and planning useful prospective investigations.