The ability of mumps virus to infect pancreatic Beta cells and cause alterations in their HLA expression was evaluated in cultured human fetal islet cell clusters. Mumps virus could be isolated during the whole culture period (6-8 days) and 60% of cells, including Beta cells, contained viral nucleocapsid protein at the end of the culturing. A minor decrease in insulin secretion was observed in some of the infected cultures. The infection was invariably associated with an increase in the expression of HLA class I molecules. This enhancement was mediated by soluble factors secreted by infected cells. The infection could not induce the expression of HLA-DR molecules. However, external interferon-gamma was able to cause a clear rise in DR-expression which was observed only on non-Beta-cells. Rubella and coxsackie B4 viruses were also able to enhance the expression of class I molecules while herpes simplex virus type 2 was not. The results suggest that certain viruses are able to infect Beta cells and cause alterations in their immunological appearance. Increased HLA class I expression in infected islets may exaggerate the autoimmune process in pre-diabetic individuals by increasing the activity of autoreactive cytotoxic T cells.

Haapala AM, Hyöty H, Parkkonen P, Mustonen J, Soppi E. Antibody Reactivity Against Thyroid Peroxidase and Myeloperoxidase in Autoimmune Thyroiditis and Systemic Vaculitis. Scand J Immunol 1997;46:78-85 Potential cross-reactivity between thyroid peroxidase (TPO) and myeloperoxidase (MPO) molecules was evaluated by analysing the binding of 199 TPO antibody-and 145 MPO antibody-positive sera to TPO and MPO molecules. Sera from six patients with autoimmune thyroiditis (AITD) and four patients with systemic vasculitis (SV) with different TPO-MPO antibody findings were then chosen for further analyses. All six patients with AITD had TPO antibodies in enzyme immunoassay (EIA) and four of them had simultaneously MPO antibodies in EIA. In AITD patients antibody binding to TPO could not be inhibited by adding native MPO to the serum diluent, suggesting that the possible cross-reactive epitopes were exposed in the denaturated MPO molecule. Similarly, the MPO ab reactivity of patients with systemic vasculitis could not be inhibited by native TPO. To study whether TPO and MPO antibodies recognize linear epitopes, the binding of antibodies to synthetic TPO and MPO peptides was analysed. Several TPO and MPO peptides were reactive, including peptides reacting with both TPO and MPO antibody-positive sera. One of the most crossreactive peptides contained AA 586-601 in TPO, showing also particularly high AA homology (88%) with MPO (AA 594-609). The results suggest that TPO and MPO molecules contain cross-reactive epitopes that are exposed in denaturated molecules and may thus cause false positive antibody findings in solid phase EIA assays.

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SUMMARYA five amino acids-long sequence (GPPAA) in Iho region of Ihc 57th amino acid of HI..A-DOS /( chain, vt'hich seems to be imporlant in delining the risk for type I diabetes, occurs LUSO in the BERF4-cncoded EBNA.IC protein of Epstein-Barr virus {EBV) in six successive repeats. The antigenicity of this region was analysed using synthetic peplidcs containing different modifications of ihe GPPAA sequence. Tvt'OoCthc seven individuals who had acute EBV infeclion produced antibodies against an EBV-derivcd peplide (GPPAAGPPAAGPPA A) paralleling the EBNA: antibodies. These two cases also conlracled type I diabetes immediately after ihe infection. High antibody levels against this peptide were Ibund in a total of 12' V-;, of EBV ' individuals, and in most cases antibodies remained at high levels for several years. Human sera as well as aHinily-purificd aniibodies specific for the CiPPAAGPPAAGPPAA peptide reacted also with shorter peptide analogues (GPPAAGPPAA and GPPAA). as vi-ell as with peptides containing the surrounding niotits from DQH ji chains. However, none of these antibodies bound to denatured DQ8 fi chains in immunoblotting. The charge of the 57th amino acid modulated the antigenicily of this epitope. as peptides from Asp-57-negative DQ molecules were reaciive, while peptides from Asp-57-positive DQ molecules were not. The responsiveness was seen in both HLA-DQS-positive and -negative subjects as well as in type I diabetic individuals. The results suggest that some individuals who carry the GPPAA sequence in their HLA-DQ molecule recognize ihis epitope in EBV. This phenomenon may have potential importance in EBV-induced immune abnormalities, although cross-rcactiviiy against DQ molecules could no! be demonstrated in the present study.