The aim was to study whether different strains of Coxsackievirus B4

An improved method for the detection of deoxythymidine kinase (TK) in human sera is reported. The method which utilizes 125I-iododeoxyuridine (IdUrd) as a substrate was used to measure TK in sera from patients with different diseases. Sera collected during the acute stage of infectious mononucleosis were found to contain elevated levels of TK, in most cases 10-40 times the normal value. The serum TK activity disappeared gradually and reached a normal level within 4 weeks. Sera from patients with other viral infections contained in most cases normal serum TK levels except in connection with measles, rubella, varicella, herpes simplex virus and cytomegalovirus infections. Additional studies revealed that sera from patients with different types of advanced lymphomas, acute leukemias, chronic granulocytic leukemia and lung cancer of the small-cell type with metastases, contained high TK levels which fluctuated in parallel with alterations in activity of the disease. The TK activity in sera from patients with both mononucleosis and tumor disease was characterized by electrophoresis and by its ability to utilize cytidine triphosphate as the phosphate donor. The results showed that the serum TK has the same properties as the human cytosolar TKI, except in connection with varicella.

Summary In a population-based setting, we traced serum samples collected at time of birth from 55 mothers whose children later developed insulin-dependent diabetes (IDDM) and .matched them pairwise to control subjects who gave birth at the same hospital during the same month. The sera were analysed for IgM antibodies to coxsackie B virus serotypes 2, 3 and 4 (CBV-2, 3 and 4) using a type-specific w-antibody-capture radioimmunoassay. Despite a decreased power due to the close matching by time of birth we found a significantly higher frequency of CBV-3 IgM at delivery in mothers whose children later became diabetic compared to their matched control subjects. When using the presence of CBV-3 IgM as a risk factor the Mantel-Haenszel odds ratio estimate (95 % confidence limits) was 2.57 (1.02; 7.31), p = 0.043. For CBV-2 and CBV-4, respectively no significant difference was found between mothers of patients and control subjects. According to the odds ratio estimate for CBV-3 and the proportion of exposed mothers among patients estimated in this study the aetiological fraction for this risk determinant would be 27 %. In conclusion, this study indicates that children of mothers who expressed CBV IgM at delivery are at increased risk for developing childhood onset IDDM. A fetal infection with CBV similar to rubella virus may initiate autoimmunity or cause persistent infection that may lead to progressive beta-cell destruction. [Diabetologia (1995[Diabetologia ( ) 38: 1371[Diabetologia ( -1373 Key words Pregnancy; Coxsackie B virus viral infections; Childhood IDDM. Viral infections, especially due to picornaviruses, have long been suspected to be associated with insulin-dependent diabetes (IDDM) and evidence for such a mechanism has been collected in a large number of animal experiments. Viruses may directly infect and destroy the beta cells, as indicated from one case report where coxsackie B4 virus (CBV-4) was isolated from the pancreas of a child who died a few days after the onset of IDDM. Viruses may also more unspecifically precipitate disease onset by increasing the work load of an already damaged beta- cell, a mechanism which is suggested by the discovery of a dose-response relationship between the risk for IDDM and the frequency of recent infections. In humans, the most convincing evidence of virus as an early initiator of IDDM was the discovery of a very high prevalence of diabetes in a cohort of children who were followed-up because of fetal rubella embryopathy syndrome [1]. The rubella embryopathy syndrome is now virtually eradicated in Sweden due to vaccination programmes but other fetal virus infections might also affect the vulnerable immature immune system and thereby initiate autoimmunity to the beta cell.In a recent population-based case-control study we found that mothers whose children later became diabetic had higher titres of group-specific enterovirus antibodies at time of giving birth when compared to mothers whose children were healthy, whereas no difference was found in antibody titres to herpes,

In a population-based setting, we traced serum samples collected at time of birth from 55 mothers whose children later developed insulin-dependent diabetes (IDDM) and matched them pairwise to control subjects who gave birth at the same hospital during the same month. The sera were analysed for IgM antibodies to coxsackie B virus serotypes 2, 3 and 4 (CBV-2, 3 and 4) using a type-specific mu-antibody-capture radioimmunoassay. Despite a decreased power due to the close matching by time of birth we found a significantly higher frequency of CBV-3 IgM at delivery in mothers whose children later became diabetic compared to their matched control subjects. When using the presence of CBV-3 IgM as a risk factor the Mantel-Haenszel odds ratio estimate (95% confidence limits) was 2.57 (1.02; 7.31), p = 0.043. For CBV-2 and CBV-4, respectively no significant difference was found between mothers of patients and control subjects. According to the odds ratio estimate for CBV-3 and the proportion of exposed mothers among patients estimated in this study the aetiological fraction for this risk determinant would be 27%. In conclusion, this study indicates that children of mothers who expressed CBV IgM at delivery are at increased risk for developing childhood onset IDDM. A fetal infection with CBV similar to rubella virus may initiate autoimmunity or cause persistent infection that may lead to progressive beta-cell destruction.

Thirty-five children with newly-diagnosed Type 1 (insulin-dependent) diabetes mellitus and their 47 siblings were investigated for the presence of IgM antibodies to Coxsackie B virus serotypes 1-5 (CBV 1-5) with the aid of mu-antibody-capture radioimmunoassays. When a high cut-off value was used, 16 (46%) diabetic children and 16 (34%) siblings showed CBV-IgM. Of the siblings of diabetic patients positive for CBV-IgM, 11 (44%) were CBV-IgM-positive; the corresponding figure for the siblings of negative patients was five (26%). With a lower cut-off value, leading to a "borderline titre", the frequency of IgM positivity increased in both the patients and siblings. When the borderline titres were included, the number of IgM-positive patients was 19 (54%) and the corresponding number of siblings was 29 (62%). Of the siblings of positive patients, 27 (93%) showed CBV-IgM, and of the siblings of the negative patients, two (11%) were CBV-IgM-positive. Sixteen (89%) siblings of IgM-negative patients remained negative. Regarding the serotypes of CBV to which IgM was directed, CBV 4 was most frequent, followed by serotypes CBV 3, CBV 2, CBV 5 and CBV 1. There was a striking similarity between the individual diabetic child and his or her sibling(s) concerning this specificity of IgM. It is concluded that within most families with a newly-diagnosed diabetic child positive for CBV-IgM the same serotype(s) of the virus circulates and that the intrafamilial spread of virus is considerable. The results strongly indicate that the IgM detected was CBV-specific and caused by a recent or current CBV infection.(ABSTRACT TRUNCATED AT 250 WORDS)