Serum p53 accumulation and altered antibody responses to Epstein-Barr virus proteins precede diagnosis of haemopoietic malignancies of lymphoid origin.

We analysed antibodies to Epstein-Barr virus nuclear antigens (EBNAs 1, 2, 5 and 6) and the presence of serum p53 in 100 individuals, 37 of whom has developed a haemopoietic malignancy during a 12-year follow-up of 39,000 Finnish adults. Serum p53 was detectable in six of the 63 (10%) matched controls and in 13/31 (42%) patients who developed a malignancy of lymphoid origin approximately 7 years after serum withdrawal. Six patients who developed a malignancy of myeloid origin were negative for p53. The presence of p53 alone was associated with a highly significant increased risk of lymphoid malignancies (relative risk (RR)p53 = 6.7, 95% confidence limits (CL) 1.9, 24) whereas high levels of antibody to EBNA2 seemed to be inversely related to the risk (RREBNA2 = 0.1, CL 0.0, 1.1). Among lymphoid malignancies, a combination of serum p53 and high EBNA1 antibody levels gave a greater than expected risk (RRp53 and EBNA1 = 14, CL 1.4, 130; RRexpected = 4.4), whereas interaction with high levels of EBNA5 antibody gave an expected risk (RRp53 and EBNA5 = 19, CL 1.7, 220; RRexpected = 17). Thus detectable levels of p53 appear early in the development of lymphoid malignancies, and high EBNA1 antibody levels, and accumulated p53 may both be synergistic risk indicators for lymphoid malignancies, whereas high EBNA5 antibody levels and accumulation of p53 seem to raise the RR independently of each other.

Antibody response to adenovirus E1b-derived synthetic peptides and serum levels of p53 in patients with gastrointestinal and other malignant lymphomas.

Serum levels of p53 and antipeptide antibody levels to adenovirus type 12 (Ad12) E1b protein were measured in a case-control study of 62 newly diagnosed patients with malignant lymphoma. While patients with gastrointestinal lymphoma did not differ from their matched controls, p53 positive lymphoma patients had significantly (P < 0.04) increased antipeptide IgG antibody levels to the Ad12 E1b. Concomitant detection of serum p53 and antipeptide antibodies to Ad12 E1b was associated with an increased risk (OR = 17.0, 95% confidence limits 1.5, 58.5) of malignant lymphoma suggesting synergism between expression of Ad12 E1b and accumulation of p53 in patients with malignant lymphoma.

Antibody response to B cell epitopes of Chlamydia trachomatis 60-kDa heat-shock protein and corresponding mycobacterial and human peptides in infants with chlamydial pneumonitis.

To study antibody response to the hypersensitivity protein B of Chlamydia trachomatis, also known as the 60-kDa heat-shock protein (hsp60), epitope scanning was done over the entire protein. Human sera with antibodies to C. trachomatis identified 5 major antigenic regions (peptides 2, 5, 9, 17, and 21) and several minor regions (peptides 34-37, 39, 50, and 59-62). Clear-cut IgG antibody responses to chlamydial peptide 2 (YNEEARKKIQKGVKT) and a corresponding mycobacterial peptide (YDEEARRGLERGLNA) were found in 8 of 16 infants with chlamydial pneumonitis and in 1 of 18 controls. Peptide 50 (RLAKLSGGVAVIRVG) showed an 80% identity with its human counterpart (RLAKLSDGVAVLKVG), which was derived from human mitochondrial protein P1, but specific antipeptide antibody responses were found in 3 of 16 cases only. In summary, both IgG antibody response to C. trachomatis hsp60 and occasional autoantibody formation in infants with chlamydial pneumonitis were found.

Antibodies to E1b protein-derived peptides of enteric adenovirus type 40 are associated with celiac disease and dermatitis herpetiformis.

Sera from 41 children with untreated celiac disease (CD), and 16 children with dermatitis herpetiformis (DH), and 57 matched controls were studied for serum antibodies to synthetic peptides derived from an early E1b protein of adenovirus type 12 and type 40 (Ad12, Ad40) and A-gliadin. In addition to peptides which share homology with A-gliadin, "nonhomologous" peptides derived from Ad12 and Ad40 E1b proteins were used as antigens in ELISA. Patients with CD and DH had significantly higher IgG antibody levels than those of controls to the nonhomologous Ad40 E1b peptide. Concomitant presence of antipeptide IgA antibodies to A-gliadin and Ad12 E1b or Ad40 E1b peptides (which share no homology with A-gliadin) increased the risk of CD/DH suggesting that both adenovirus infections and gluten exposure contribute to the development of CD/DH.

Antipeptide antibodies to adenovirus E1b protein indicate enhanced risk of celiac disease and dermatitis herpetiformis.

The relationship between adenovirus type 12 (Ad12), celiac disease (CD) and dermatitis herpetiformis (DH) was evaluated by enzyme-linked immunosorbent assay (ELISA). Diagnostic phase serum samples from 44 children with CD, 16 children with DH and 60 matched controls were studied for serum antibodies to synthetic peptides derived from an early E1b protein of Ad12 and A gliadin. Both the patient groups had significantly (p < 0.001) higher IgG antibody levels to the Ad12 E1b peptide than the controls. The difference was especially pronounced for girls (p < 0.005). Antipeptide IgG antibodies to Ad12 E1b and A gliadin posed a synergistic increase in the CD and DH risk suggesting that infection with Ad12 is associated with CD and DH.

Determination of antibodies to non-structural and structural adenovirus antigens by ELISA.

We evaluated possibilities to analyze serum antibodies to non-structural (peptides derived from adenovirus E1b protein) and structural (hexon) adenovirus antigens by ELISA. Synthetic dodecapeptides covering a putative A-gliadin cross-reactive antigenic determinant of the E1b protein were used. The aminoterminus of the peptides appeared to be important for antibody binding but the exact sequence of a possible common B-cell epitope within the peptides remained open. Coupling of the peptides to a carrier protein was essential for ELISA analyses of serum antipeptide antibodies. IgA antibodies to both adenovirus derived E1b peptides and hexon antigen could be detected already two weeks after the onset of an acute adenovirus infection, while antipeptide IgG antibodies were seen in a restricted number of patients only.

Postpubertal gluten challenge in coeliac disease.

Altogether 38 postpubertal children with coeliac disease were rebiopsied. Mucosal abnormality in nine (24%) of them indicated poor adherence to the diet. Gluten challenge with a diet containing a normal amount of gluten was performed in those 29 patients with a normal mucosa. During challenge, rebiopsy was done when reticulin antibodies turned positive (mean 0.6 years, range 0.2-2.0) or at the end of the two year study. Histologically a clear relapse into coeliac disease was seen in all 23 patients who were positive for reticulin antibodies. At this time gliadin antibodies were positive in all but two. Sixteen (70%) of those who relapsed were completely asymptomatic. Three girls and one boy did not relapse within two years, indicating the possible recovery from coeliac disease to be 11%. All four had undergone gluten challenge earlier in childhood, after initial diagnosis and mucosal recovery, and this had resulted in mucosal relapse. To establish definite postpubertal recovery from coeliac disease in cases with normal mucosa at two years from challenge, further follow up studies of reticulin antibodies and later rebiopsy are needed. The reticulin antibody test seems to be suitable for prediction of mucosal relapse in coeliac disease.

Changing pattern of childhood coeliac disease in Finland.

In the Tampere region in Finland, the incidence of childhood coeliac disease was 1:1,096 between 1964 and 1973 and 1:3,214 from 1974 to 1983. The clinical picture of coeliac disease had changed to milder forms, resulting in an upward shift of age at diagnosis. Coeliac disease was found in older children and adolescents, manifesting itself mostly in minor abdominal symptoms, short stature, delayed puberty, anaemia and joint complaints, and in children with diabetes mellitus. Long breast-feeding seemed to postpone the symptoms but the introduction of gluten was of no significance. The low incidence for 1974 to 1983 was thought to be due to the estimated 20 cases born in 1979 to 1983 who were not detected. We do not believe that coeliac disease has disappeared but that it will be found during the next decade in the patients who were not diagnosed in school age and adolescence.