We investigated whether the development of spontaneous T-cell-mediated type I diabetes in NOD mice is influenced by B cells and immunoglobulin (Ig). During the first 4 weeks of life, B-cell development was suppressed by repeated administration of rabbit anti-mouse IgM (RaIgM), while controls received polyclonal rabbit Ig (NRIg). A reduction in the incidence of diabetes, as well as in development of insulitis, was observed after either of these treatments. However, the effect on insulitis was more pronounced in mice treated with RaIgM compared with those treated with NRIg. Furthermore, while the optimal effect of NRIg was obtained after a single injection at birth, the additional effect of RaIgM on development of insulitis was observed only after continued treatment for the first 4 weeks of life. Taken together these data suggest a possible role of Ig/B cells in the development of autoimmunity in the NOD mouse. The additional effect observed after continued suppression of the neonatal B-cell development suggests that this population may contribute significantly to the establishment of an auto-aggressive lymphocyte repertoire in the NOD mouse.
Abstract. Eriksson JW, Carlberg B, Hillo Èrn V (Umea Ê University Hospital, Umea Ê, Sweden). Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia (Case Report). J Intern Med 1999; 245: 307]10.We report on a patient with hypokalaemia and severe ventricular tachycardia of torsades de pointes type which turned out to be caused by an apparent mineralocorticoid excess syndrome associated with liquorice consumption. The patient, a 44-year-old woman, attended the hospital because of irregular heart rhythm and she displayed repeated episodes of life-threatening torsades de pointes ventricular tachycardia. The initial serum potassium was low:
mmol L
21. The patient was treated with potassium and magnesium infusions, and the dysrhythmias eventually ceased. Endocrinological investigations showed no indication of Cushing's syndrome or hyperaldosteronism. After some time it became clear that the patient had ingested moderately large amounts of liquorice every day for 4 months. After the patient stopped this habit the hypokalaemia and dysrhythmias did not recur and after more than 1 year there are no signs of cardiac illness.
We have characterized the peripheral B cell repertoire in T cell‐mediated insulin‐dependent diabetes mellitus (IDMM) and in B cell‐mediated autoimmune idiopathic thrombocytopenic purpura (AITP). The VH6‐containing repertoire in adult patients with IDDM or AITP and healthy control subjects was investigated by PCR amplification using VH6‐ and JH‐specific primers. Nucleotide sequence analysis of VH6‐D‐JH rearrangements showed an abnormally high frequency of somatic mutations in non‐functional rearrangements from diabetic (3.58 %) as well as AITP patients (3.18 %), compared to controls (0.4 % and 1.43 %, respectively; p < 0.05). In contrast, the mutation frequency among functional rearrangements was 2.4 – 3 times lower in patients compared to controls ( p < 0.05). Detailed analysis of the VH6 genes carrying mutations showed that the underlying mechanism for this observation is probably different for the two diseases. Analysis of D‐ and JH gene usage revealed additional deviations from the normal pattern. Taken together, these results suggest defects in the mechanisms controlling selection of the B cell repertoire in patients with IDDM or AITP.
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